26870816_1 newly generated mir-23a destabilizes keap1 mrna by binding to its 3'utr. 26870816_2 mir-23a overexpression led to a statistically significant decrease in luciferase expression, showing that keap1 mrna was a direct mir-23a target . 26870816_3 this regulation was physiologically relevant, because cells that overexpressed mir-23a increased expression of endogenous nqo-1 mrna . 21885851_1 as shown in figure 2a to 2c, both mir-16 and mir-424 significantly decreased vegfr2, fgfr1, and vegf protein and mrna levels. 21885851_2 importantly, inhibition of endogenous mir-16 or mir-424 increased the expression of vegfr2, fgfr1, and vegf at both the protein and mrna levels . 21885851_3 the targeting activity of these mirnas on vegfr2 and fgfr1 was also relevant for human aortic ecs , a human adult ec type from a different vascular bed than huvecs. 21885851_5 as shown in figure 3c, stimulation of huvecs with vegf reduced both vegfr2 and fgfr1 3'-utr activity, whereas no effect was observed when cells were transfected with the empty vector control, indicating that some endogenous mirnas involved in the regulation of vegfr2 and fgfr1 were induced to regulate their expression under stimulated conditions. 21885851_6 interestingly, endogenous inhibition of mir-16 or mir-424 before vegf stimulation restored vegfr2 and fgfr1 3'-utr activity , indicating that these effects are likely to be mediated by mir-16 and mir-424 upregulation in ecs. 21885851_7 altogether, these data indicate that mir-16/-424 regulates cell-intrinsic angiogenic responses in vitro and are consistent with their targeting activity on vegfr2, fgfr1, and vegf in ecs. 21885851_8 altogether, these data suggest that these mirnas are likely to control proliferation, migration, and differentiation of ecs by regulation of vegf and bfgf signaling through vegfr2 and fgfr1. 25658461_2 we found that transfecting mscs with mir-133a mimic improves survival of mscs as determined by the mtt assay. 25658461_3 similarly, transplantation of mir-133a mimic transfected mscs in rat hearts subjected to mi led to a significant increase in cell engraftment, cardiac function, and decreased fibrosis when compared with mscs only or mi groups. 25658461_4 at the molecular level, quantitative real-time polymerase chain reaction data demonstrated a significant decrease in expression of the proapoptotic genes; apaf-1, caspase-9, and caspase-3 in the mir-133a mimic transplanted group. 25658461_5 furthermore, luciferase reporter assay confirmed that mir-133a is a direct target for apaf-1. 20466882_1 these studies show that abca1 expression is repressed by excess mir-33, especially in mouse j774 macrophages and the human imr-90 fibroblasts . 20466882_2 taken together,these findings demonstrate that abca1 protein expression is regulated by mir-33a/b. 20466882_3 together, these results suggest that mir-33a/b inhibit expression of human abca1 by targeting the abca1 3'-utr for translation repression or mrna degradation. 20466882_4 these findings demonstrate that mir-33 posttranscriptional repression of abca1 results in retention of intracellular cholesterol in macrophages and are in keeping with our hypothesis that mir-33 regulates cholesterol trafficking by controlling abca1 levels. 23305858_1 our observations also suggest that hsa-let-7 g acts as a critical regulator of autophagy and apoptosis by modulating lox-1. 24833879_3 this observation indicated that fn1 was one of the potential targets of mir-204-3p. 24833879_4 after over-expression of mir-204-3p in hcc tecs, western blot analysis showed that the expression of fn1 protein was significantly inhibited. 23894411_1 mir-19a has been shown to regulate socs1 expression during mutiple myeloma and be induced by the anti-viral cytokine interferon- -alpha, suggesting a role in the regulation of the jak-stat pathway. 26572705_1 in addition, vhl was identified as a functional target of mir-566. in the present study, vhl was identified as a functional target of mir-566, and was shown to regulate the expression of vegf by targeting hif-1 alpha for degradation. 26572705_2 these results indicate that the vhl gene is a direct target of mir-566. 26572705_3 furthermore, the invasive and migratory abilities of the cells may be suppressed following the inhibition of mir-566, suggesting that mir-566 is able to modulate vegf by targeting vhl in vivo. 22482882_1 ipc enhances stem cell survival via the combined participation of hypoxia responsive mirs mir-107 and mir-210 via their respective putative target genes pdcd10 and casp8ap2. 21816922_1 p21cip1 is a well-characterized target for mir-17-92 family members, with a 3'-untranslated region that is directly regulated by micrornas in the mir-17/mir-20/mir-106 family . 21816922_2 p57kip2 is also a validated mir-17-92 target with a 3'-utr harboring binding sites for mir-92 . 21816922_3 mir-17-92 status was not associated with alteration in the protein levels of another cdki that is also up-regulated uponrb/p107 loss, p18ink4c, but lacks 3'-utr-binding sites for mir-17-92 family members . 21816922_4 interestingly, p130 protein levels were also reduced when mir-17-92 was overexpressed together with rb/p107 deletion . 21816922_5 p130 has also been reported to be a direct target for mir-17-92-encoded micrornas . 21816922_6 inhibition of mir-17/20 also led to up-regulation of p21cip1, consistent with p21cip1 being a direct reported target of mir-17/20 . 21816922_7 these data indicate that mir-17/20 inhibition suppresses proliferation in retinoblastoma cell lines, while mir-19 inhibition has little consequence. 21816922_8 moreover, our observations of p21cip1 up-regulation upon mir-17-92 inhibition in human retinoblastoma cells and p21cip1 suppression upon mir-17-92 overexpression in murine retinas suggested that p21cip1 may be a critical mir-17-92 target in retinoblastoma. 22203953_2 coinjection of anti-bcl-2 antibody in zygotes partially reversed but injection of bcl-2 protein mimicked the effect of mir-34c inhibition. 22203953_3 oocyte activation is essential for the mir-34c action in zygotes, as demonstrated by a decrease in 3'utr luciferase reporter activity and bcl-2 expression after injection of precursor mir-34c into parthenogenetic oocytes. 22203953_4 fig.3 bcl-2 is a target of mir-34c. 22203953_5 we also found lower bcl-2 3'utr reporter activities in parthenogenic oocytes injected with precursor mir-34c . 22203953_6 bcl-2 mediates the action of mir-34c on the first cleavage. 22203953_7 bcl-2 is a direct target of mir-34c, as shown by reporter assay and western blotting in jar cells and zygotes. 25175832_1 furthermore, we found that mir-124a directly targeted and suppressed iq motif containing gtpase activating protein 1 , a well-known regulator of actin dynamics and cell motility. 25175832_2 iqgap1 is a direct target of mir-124 a in the u87 cells. 25175832_3 the results demonstrated that iqgap1 is a direct target of mir-124a. 25175832_4 luciferase assay demonstrated that iqgap1 is a direct target of mir-124a. 20558762_2 since mir-802 and the hat1r protein are expressed in similar colon cell types, this suggests that mir-802 may play a physiological role in regulating the expression of the hat1r in the gi system. 20558762_3 these results indicate that mir-802 can interfere with luciferase mrna translation by direct interaction with the hat1r 3'-utr at the predicted targetsite. 20558762_4 taken together, gain-of-function experiments suggest that mir-802 can decrease hat1r expression by inhibiting translation of the mrna, rather than targeting for degradation 22094713_1 furthermore, we verified that mir-29b directly targeted and inhibited bcl2l2 gene expression, and then increased neuronal cell death. 22094713_2 importantly, bcl2l2 overexpression rescued neuronal cell death induced by mir-29b. 22094713_3 mir-29b targets and inhibits bcl2l2 gene expression. 22094713_4 these observations confirmed that mir-29b inhibited the expression of endogenous anti-apoptotic bcl-2 family members in neuronal cells. 22094713_5 these data confirm that mir-29b promoted neuronal cell death, at least in part, by repressing bcl2l2. 26918829_1 pten is a well-known target gene of mir-19b . in the current study, immunoblot analysis showed that pten was inversely regulated by mir-19b in h9c2 cells. 26918829_2 qrt-pcr analysis for mir-19b level in h9c2 cardiomyocytes transfected with mir-19b mimic, inhibitor, or respective negative controls . 26918829_3 these data suggest that pten is responsbile for the effects of mir-19b in h2o2-induced apoptosis in h9c2 cardiomyocytes . 25613180_1 this study demonstrated that biochanin a promoted eralpha-positive cell proliferation through mir-375 activation and this mechanism is possibly involving in a mir-375 and eralpha feedback loop. 18278031_2 mir-223 mutant mice have an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors. 18278031_3 mef2c, a transcription factor that promotes myeloid progenitor proliferation, is a target of mir-223, and that genetic ablation of mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in mir-223 null mice. in addition, granulocytes lacking mir-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. 26260688_1 bioinformatic analysis using the targetscan and miranda algorithm indicated that the 3'utr of hif-1alpha contained a predicted binding site for mir-338-3p . 26260688_2 to demonstrate that mir-338-3p directly targets hif-1alpha by interacting with its 3'-utr, we co-transfected the pgl luciferase reporter plasmid harboring the wild-type or mutant 3'-utr of hif-1alpha, along with mir-338-3p or nc mirna . 26260688_3 overexpressed mir-338-3p resulted in significant reduction of hif-1alpha 3'-utr firefly luciferase reporter activity containing wild-type but not mutant binding sites compared to that of nc-mirna. 26260688_4 in summary, these results indicate that hif-1alpha was a direct target gene of mir-338-3p in npc cells. 26260688_5 immunofluorescence staining revealed that hif-1alpha expression was inhibited by transfection with mir-338-3p mimics and was promoted by transfection with mir-338-3p inhibitor. 19155302_1 mcl-1 is a direct target of mir-101. 19155302_3 we found that ectopic expression of mir-101 caused a dose-dependent decrease in mcl-1 protein but not mrna level . 19155302_4 moreover, inhibition of endogenous mir-101 by synthetic mir-101 inhibitor resulted in up-regulation of the mcl-1 protein . 19155302_5 these data suggest that mir-101 may inhibit the expression of mcl-1 at posttranscriptional level by directly targeting the 3'-utr of mcl-1 mrna. 22287560_1 combining global gene expression analyses of mir-30a-5p transgenic line hct116 with in silico mirna targetprediction, we identified the denticleless protein homolog as a potential mirna-30a-5p target subsequent reporter gene assays confirmed the predicted mir-30a-5p binding site in the 3'untranslated region of dtl. 22287560_2 importantly, overexpression of dtl in hct116 cells partially rescued these cells from mir-30a-5p-mediated growth suppression. 22287560_3 mir-30a-5p regulates dtl directly via both predicted mir-30a-5p binding sites. 22287560_5 taken together, these results indicate that mir-30a-5p regulates dtl directly via both predicted mir-30a-5p binding sites. 22287560_7 4.luciferase assay: mir-30a-5p target dtl. 26881967_1 here, we demonstrate that in heterogeneous gsc, mir-10b regulates cell cycle and alternative splicing, often through the non-canonical targeting via 5 ' utrs of its target genes, including mbnl1-3, sart3, and rsrc1. 26881967_2 deletion of mir-10b binding sites completely reversed the regulation of mbnl2 and mbnl3 5 ' utrs, confirming direct targeting of these splicing factors through their 5 ' utrs . 26881967_3 altogether, these results indicate that mir-10b directly binds to and fine-tunes expression of multiple splicing factors in gsc, through their 5 ' utrs and 3 ' utrs, via both seed- and non-seed-mediated targeting. 26881967_4 furthermore, expression of many rna-binding proteins involved in splicing appeared regulated by mir-10b; among them, we validated several regulators of alternative splicing as direct mir-10b targets. 26881967_5 these new targets included the mbnl family , sart3, rsrc1, srsf11, ptbp2, and dgcr14. 21958558_1 mir-181 targets multiple bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes. 21368194_1 the case of let-7 is particularly exciting because it targets cdc34 and leads to wee1 stabilization and g2/m accumulation . 21368194_3 most importantly, the restoration of the expression of tumor-suppressor mirnas in rko cells upon enoxacin treatment was associated with the down-regulation of their respective target oncoproteins, as we observed for myc and k-ras . 21368194_4 the restoration of the expression of tumor-suppressor mirnas in the tumors upon enoxacin treatment was associated with the down-regulation of their respective target oncoproteins, such as we observed for myc and k-ras . 26184978_1 on each foxn3 and atp8a1 3'-utr, there are also target positions predicted for the two mirnas . 26184978_2 then, we cloned the 3'-utr fragments of foxn3 and atp8a1 containing the putative mir-135b-5p or mir-499a-3p corresponding binding sequence into a luciferase reporter construct, respectively. 26184978_3 indeed, overexpression of mir-135b-5p or mir-499a-3p significantly inhibited the luciferase activity of wt 3'-utr of foxn3 , whereas there was no significant reduction in luciferase activity when cotransfected with mir-135b-5p and its corresponding pmirglo-atp8a1-wt . 26184978_4 it will be interesting to study the regulations by which mir-135b-5p and mir-499a-3p target foxn3 gene in further studies; 22782903_2 matrix metallopeptidase 13 was identified as a direct target suppressed by mir-125b, and there was an inverse relationship between the expression of mir-125b and mmp13 in cscc. 22782903_3 thus, knockdown of mmp13 can phenocopy the effects of overexpression of mir-125b in cscc cells, indicating that mmp13 is a key mediator of the tumor suppressive effects of mir-125b in cscc. 26307684_1 here we report that caspase3 and caspase7 are previously unidentified targets of mir-224 in nsclc, and that mir-224 promotes lung cancer cells proliferation and migration in part by directly targeting casp7 and down-regulating its expression. 26307684_2 here, we show that mir-224 is involved in the lung cancer pathogenesis through direct targeting of casp3 and casp7. 26307684_3 co-transfection of mir-224 with the 3'-utr mutants of either casp3 or casp7 significantly impaired the reduction capability of mir-224 on the luciferase activity of corresponding wild-type 3'-utrs , suggesting that mir-224 negatively regulates casp3 and casp7 expressions by directly interacting with their 3'-utrs. 26307684_4 in summary, these results confirm that mir-224 directly targets casp3 and casp7 in lung cancer cells. 18953042_1 data clearly show that the 5'terminal region of omra/b interacts in vivo with the tir of cira mrna and that a relatively short pairing region of no more than 9 nt is sufficient for the regulation, at least when omra/b are overexpressed. 23449803_1 gene expression profiling of huh-7.5 cells showed that mir-27a regulates lipid metabolism by targeting the lipid synthetic transcription factor rxralpha and the lipid transporter atp-binding cassette subfamily a member 1. interestingly, the expression of mir-27a was upregulated by hcv infection and lipid overload through the adipocyte differentiation transcription factor c/ebpalpha. in turn, upregulated mir-27a repressed hcv infection and lipid storage in cells. 26202084_1 the target of mir-135a and the protein expression of klf4 and stat4. 19506341_2 through bioinformatics, we identified the potential target sites for mir-1 on the 3' utr of bcl-2. 19506341_3 mir-1 significantly reduced the expression of bcl-2 in the levels of mrna and protein. 19506341_5 these data demonstrated that mir-1 plays an important role in the regulation of cardiomyocyte apoptosis, which is involved in post-transcriptional repression of bcl-2. 25694126_1 thermo-chemotherapy induced invasion suppression through mir-218 and its downstream target gli2. 25694126_2 in vitro experiments were further carried out to obtain evidence of gli2 as a target of mir-218. 20176475_1 bioinformatics, gene and protein expression analysis in eight gastric cell lines identified mir-130b as the top candidate mirna for runx3 binding. 20176475_2 overexpression of mir-130b increased cell viability, reduced cell death and decreased expression of bim in tgf-beta mediated apoptosis, subsequent to the downregulation of runx3 protein expression. 26512777_1 we observed no repression in luciferase activity after mutating or deleting the binding site ,1e, suggesting that mir-22 directly interacts with the tip60 3'-utr and targets tip60. 26512777_2 these data indicate that mir-22 down-regulates endogenous tip60 expression. 26512777_3 these findings suggest that repression of tip60 by mir-22 increases cell migration and this can be reverted by ablating activity of mir-22 or through the overexpression of a tip60 that lacks mir-22 binding site. 26512777_4 thus, mir-22 stimulates cell migration by targeting tip60. 26512777_5 these results suggest that mir-22 targets tip60 leading to an increase in cell migration and invasion of breast cancer cells thereby promoting metastasis. 22891274_1 collectively, these results demonstrate traf6 and irak1 to be bona fide targets of mir-146a in primary mouse cd4 + and cd8 + t cells. 22891274_2 these results suggest that mir-146a regulation of t cell activation is likely mediated through its combinatorial modulation of multiple targets including traf6 and irak1. 22891274_3 notably, in contrast to traf6 and irak1, analysis of other signaling components mediating tcr signaling to nf-kb including the cbm complex showed no obvious difference in their steady-state expression levels between mir-146a and wt t cells , suggesting that traf6 and irak1 are likely to be the major targets of mir-146a modulating tcr signaling to nf-kb. 26657152_1 here we show that expression of a member of the forkhead family of transcription factors, foxo3, is regulated by the foxo3 pseudogene , and foxo3 circular rna, both of which bind to eight mirnas. 26657152_2 in this study, we found that the transcripts of foxo3 mrna, foxo3p and foxo3 circular rna were all targets of mir-22, mir-136*, mir-138, mir-149*, mir-433, mir-762, mir-3614-5p and mir-3622b-5p. 26180082_1 mir-129-3p and mir-29b-1 downregulate cdk6 by potentially targeting its 3'-utr. 26180082_2 these results further demonstrated that mir-29b-1 and mir-129-3p potentially target the 3'-utr of cdk7 in glioblastoma cells. 23385085_1 through in vivo sensor assay and in vitro luciferaseassay,we found that mir-960 directly binds to the 3 'utrsof smo, cos2 and fu mrnas to block their translation. 23385085_2 we confirmed the binding of mir-960 to the 3'-utrs of smo, cos2 and fu by gfp sensor assay and dual luciferase assay. 23385085_3 however, when mir-960 was induced in the dpp domain, egfp expression decreased in all three sensor lines at the a/p boundary , confirming that mir-960 can suppress smo, cos2 and fu by directly binding to their 3'-utrs. 23385085_4 these results again confirmed that mir-960 can suppress hh signaling by directly binding to the 3'-utrs of smo, cos2 and fu. 21929751_1 taken together, these data strongly suggest that notch-1 is a downstream target of mir-144 mirna and that dcamkl-1 regulates posttranscriptional control of notch-1. 21929751_2 figure 4 knockdown of dcamkl-1 and treatment with dapt downregulates notch-1 via mir-144. 22766851_1 mir-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor lef1. targetprediction databases and luciferase data showed that lef1 is a new direct target of mir-218. 22766851_2 importantly, western blot assays demonstrated that mir-218 can reduce protein levels of lef1 and mmp-9. 22766851_3 results suggest that mir-218 is involved in the invasive behavior of gbm cells and by targeting lef1 and blocking the invasive axis, mir-218-lef1-mmps, it may be useful for developing potential clinical strategies. 22766851_4 this experiment demonstrated that lef1 is a direct target of mir-218. 22766851_5 a luciferase reporter assay further confirmed the direct interaction between mir-218 and the 3'-utr of lef1 mrna . 22766851_6 these data suggest that mir-218 plays a critical role in gbm cell invasion by directly targeting and downregulating lef1, thereby decreasing mmp-9 expression, but not through timp-1. 23472141_1 mir-133a and -204/211 are known to target the master osteogenic transcription factor runx2. further assays suggest that sost, which encodes the wnt signaling antagonist sclerostin, and alkaline phosphatase are two additional targets of mir-204/211. 23472141_2 mir-141/200a has been known to target the transcription factor dlx5. since mir-141/200a has been known as dlx5-targeting mirnas , these findings also imply that osx may negatively regulate dlx5 protein synthesis via, at least in part, up-regulation of mir-141/200a. 23472141_3 however, the role of mir-192 and mir-1194 in osteogenesis is yet to be known. 23472141_4 since mir-133a and -204/211 are known as runx2-targeting mirnas , , these observations also imply that osx may modulate the cellular level of runx2 protein via in part down-regulation of mir-133a and -204/211. 26824419_1 collectively, these suggest that mir-300 directly represses vegf-c protein expression via binding to the 3'-utr of the human vegf-c gene via ilk and akt signaling. 26824419_2 in addition, we found that mir-300 directly represses vegf-c protein expression through binding to the 3'-utr of the human vegf-c gene, thereby negatively regulating vegf-c-mediated lymphangiogenesis. 26824419_3 figure 5: mir-300 directly represses vegf-c expression via binding to the 3'-utr of human vegf-c. 23383180_1 mir-24 targets pro-apoptotic proteins bim and caspase 9 in hematopoietic cells. 23383180_2 figure 3 mir-24 decreases the levels of pro-apoptotic proteins bim and caspase 9. 17179747_1 reporter activity, normalized to activity of the coexpressed firefly luciferase , was tested in transfected huh7 and hepg2 cells . in hepg2 cells,all three reporters were translated with comparable efficiency, but in huh7 cells the activity of the reporter devoid of the mir-122 sites, rl-catc, was approximately 3-fold higher than that of reporters containing mir-122 sites. 17179747_3 furthermore, during mouse liver development cat-1 mrna decreases in an almost inverse correlation with mir-122. 17179747_4 eight potential mir-122 targetsites were predicted within the human cat-1 mrna, with six in the 3'-untranslated region. 17179747_6 in summary, these studies followed the accumulation during development of mir-122 from its mrna precursor, hcr, through to identification of what may be a specific mrna target cat-1. 21328460_1 a conserved targetsite for mir-21 within the cdk2ap1-3'-utr at nt 349-370 was predicted by bioinformatics software and an inverse correlation of mir-21 and cdk2ap1 protein was observed. 21328460_2 here was no significant association with mir-21 and cdk2ap1 mrna, and the fold differences in cdk2ap1 mrna were less than that in cdk2ap1 protein. 21328460_3 these primary data suggest that mir-21 might downregulate cdk2ap1 expression at the post-transcriptional level. 21328460_5 these data suggest that mir-21 specifically downregulates cdk2ap1 at the post-transcriptional level, and that mir-21 positively regulates proliferation of hacat cells in vitro. 22929050_1 we found that mir375 inhibited autophagosome formation, as indicated by the decreased number of green fluorescent protein -lc3 puncta. in addition, both lc3-i and lc3-ii detection and bafilomycin a1 assays supported that mir375 blocked the conversion of lc3-i to lc3-ii, which is required for the elongation of the phagopore and in turn, the formation of the autophagosome. 26607349_2 4b, bak and caspase-3 mrna levels were reduced by mir-125a/b mimics and increased by mir-125a/b inhibitors. in parallel, bak and caspase-3 protein levels were both directly regulated by mir-125a/b . 26607349_3 these results suggest that bak and caspase-3 genes are directly targeted by mir-125a/b. 20665731_1 in this study, we focused on mir-29b and mir-125a, which were predicted to regulate pdpn, and demonstrated that these micrornas directly targetthe 3' untranslated region of pdpn and inhibit invasion, apoptosis, and proliferation of glioblastomas. 20665731_2 mutation of mir-29b and mir-125a interaction sites rescued the luciferase activity, thus confirming the direct interaction with pdpn 3'-utr by these micrornas. 20665731_3 these results suggest that mir-29b and mir-125a directly regulate podoplanin expression in glioblastoma cells. 20665731_4 therefore the effects on invasion by restoration of mir-29b and mir-125a are similar with the effects by downregulation of the proved direct pdpn target 24892549_1 we identified yap1 as a direct mir-375 target in crc and show that hells and nolc1 are down-stream targets. 24892549_2 knock-down of yap1 mimicked the phenotype induced by mir-375 over-expression indicating that mir-375 most likely exerts its pro-apoptotic role through yap1 and its anti-apoptotic down-stream targets birc5 and bcl2l1. 20610624_1 here, we report that mir-96 directly target the kras oncogene and functions as a tumor-suppressing mirna in pancreatic cancer cells. 20610624_2 these data suggest that mir-96 directly recognizes the 3'-utr of kras mrna and inhibits kras translation. 20610624_4 these results suggest that mir-96 could regulate cell proliferation by targeting kras. 24872388_1 mechanistic investigations revealed that oridonin upregulated bim-s by diminishing the expression of mir-17 and mir-20a, leading to mitochondria-dependent apoptosis. 20857258_1 among them, knockdown of mirna-19a by anti-mirna-19a transfection showed a positive therapeutic effect in bladder cancer cells by inhibiting cell growth and inducing cell apoptosis targeting pten through the pten/akt pathway. 8968746_1 h19 and tnnt3 in different adult skeletal muscle types express parallelly, and these genes may share an enhancer. 23691514_1 overexpression of mir-124 suppressed iaspp protein expression, upregulated expression of the downstream signaling molecule nuclear factor-kappa b , and attenuated cell viability, proliferation, and colony formation in sw480 and ht-29 colorectal cancer cells in vitro. 20081105_1 furthermore, overexpression of the putative tumor suppressor mir-22 repressed the evi1 oncogene, which is known to suppress apoptosis by stimulating phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1 signaling. 26583674_2 inhibition of mir-494 led to a significant upregulation of the chemokine receptor cxcr4 in both endothelial cells and smooth muscle cells. 26583674_4 inhibition of mir-494 also led to an upregulation of acvr1 in macrophages and of timp3 in macrophages and mast cells. 26583674_5 moreover, we observed upregulation of the selected target genes timp3, il33, and tgfb2 in the carotid arteries of mice treated with gso-494 . 23166713_1 taken together, these findings demonstrate that mir-361-5p affects the levels of secreted vegfa, further suggesting that the mirna is able to repress endogenous vegfa expression in vitro. in summary, we found that out of a panel of six mirnas targeting vegfa, only mir-361-5p levels were decreased in scc expressing high levels of vegfa, indicating that mir-361-5p dysregulation could contribute to the observed elevated vegfa levels in scc. 21816899_1 these reporter vectors carrying mutations in the target sites were insensitive to the effect of mir-1, mir-28-a, and mir-296-3p, proving that the modification of the target sites of creb1 3' utr is able to block the function of these mirna . 25536034_1 furthermore, bioinformatic prediction and experimental validation revealed that the anti-tumor effect of mir-503 was probably exerted through targeting and repressing of l1cam expression. 25536034_2 l1cam was up-regulated in osteosarcoma cell lines and primary tumor samples and the expression level of l1cam were negatively correlated with mir-503 levels in osteosarcoma tissues. 25536034_3 enforced expression of mir-503 remarkably reduced the luciferase activity of the reporter gene with the wild-type construct but not with the mutant l1cam3'utr construct, indicating mir-503 directly targeted the l1cam 3'utr. 26294080_2 these findings indicate that dicer-1 was a direct target of mir-107. 22710123_2 additionally, mir-21 also promoted dendritic cell apoptosis by targeting bcl-2. 22710123_3 mir-21 promoted apoptosis of dcs by targeting bcl-2. 22710123_4 overall, mir-21 was negatively correlated with il-12p35 mrna expression , suggesting post-transcriptional regulation of il12p35 by mir-21. 22710123_6 as shown in fig.6c, mir-21 mimics suppressed bcl-2 mrna and protein expression in bcg-infected bmdcs, while the mir-21 inhibitor showed the opposite effect, revealing an inverse correlation between bcl2 and mir-21 expression. 20371610_1 further, we identified foxo3a as a direct target of mir-155. 20371610_2 sustained overexpression of mir-155 resulted in repression of foxo3a protein without changing mrna levels, and knockdown of mir-155 increases foxo3a. in conclusion, our study reveals a molecular link between mir-155 and foxo3a and presents evidence that mir-155 is a critical therapeutic targetin breast cancer. 20371610_3 foxo3a is negatively regulated by mir-155. 20371610_4 these data indicate that mir-155 directly target foxo3a 3'-utr at the mir-155-foxo3a response element to repress foxo3a protein expression. 20864407_1 these include mir- 125a and mir-125b, shown to directly regulate erbb2 in breast cancer cells but not in prostate cancer cells , mir-205, which regulates erbb3 expression in breast cancer cells , and mir-331-3p which directly regulates erbb2 by virtue of its specific binding to two separate targetsites . 25266720_1 here, we show that tumor suppressor mir-125a directly binds to the 3'utr of esrra and represses its expression. 19398468_1 this downregulation of mir-133 and mir-590 partly accounts for the upregulation of tgf-beta1 and tgf-betarii, because our data established tgf-beta1 and tgf-betarii as target for mir-133 and mir-590 repression. 19398468_2 we subsequently evaluated the ability of mir-133 to repress tgf--beta1 expression and of mir-590 to repress tgf--betarii expression. 23226300_1 moreover, luciferase assay confirmed the direct regulation of mir-1 on protein kinase c epsilon and heat shock protein 60 . 23226300_2 these results indicate that pkcepsilon and hsp60 are direct targets of mir-1. in this study, we experimentally established pkcepsilon and hsp60 as targets of mir-1 in mice, which is in line with the detrimental role of mir-1 in the heart. 22194605_1 moreover, mir-29a can inhibit epididymal cell proliferation by targeting nasp in vitro. 22194605_2 mir-29a may inhibit epididymal epithelial cell proliferation during postnatal epididymal development by targeting nasp. 25483041_1 therefore, we further examined whether the alteration in mir-663 expression indeed had an effect on the expression of tgfb1. 25483041_2 as shown in figures 4a and b, overexpression of mir-663 led to suppression of tgfb1 at both mrna and protein levels. 25483041_4 furthermore, overexpression of mir-663 in hela cells markedly abolished the induction of tgf--beta1 with 4 gy irradiation . 25483041_5 moreover, though addition of tgf--beta1 as well as transfection of mir-663 inhibitors reduced cell survival rate, the combination of mir-663 inhibitor transfection and tgf--beta1 neutralizing antibody treatment led to a cell survival fraction that was comparable to that of the non-treated control , suggesting an interplay exists between mir-663 and tgf--beta1. 21430074_1 the mir-101 levels showed an inverse correlation with cox-2 protein expression in all 5 cell lines . 21430074_2 cox-2 as a direct target for mir-101 regulation was determined by using a luciferase reporter assay. 21430074_3 the results indicate that mir-101 does not affect cox-2 mrna transcription. 21430074_4 these data suggest that mir-101 suppresses cox-2 protein expression by directly binding to the 3'-utr of cox-2 mrna. 21430074_5 interestingly, the inhibitory function of mir-101 on cox-2 expression can be reversed by introduction of the 3'-utr fragment of cox-2 . 21430074_6 cox-2 protein levels were significantly lower in bph1cmir101 cells than in bph1cvec cells; however, the protein level of cox-2 in bph1cmir101 cells was significantly recovered by introducing 3'-utr of cox-2 fragments . in conclusion, mir-101 negatively regulates cox-2 protein expression by specifically binding to the 3'-utr of the cox-2 mrna region. 21743493_1 in particular, we demonstrate that satb1 is not only a direct target of foxp3 repression, but that foxp3 also induces two mirs, mir-7 and mir-155, which specifically target the 3'-utr of satb1 to further regulate its expression. 21743493_2 we observed similar mir-7 and mir-155 downregulation of satb1 3'-utr reporter construct activity in mda-mb-231 cells, a second breast cancer line known to express high levels of satb1 . 21743493_3 these observations suggest that the satb1 3' -utr contains functional binding sites for mir-7 and mir-155, and together the level of these two mirs contribute to the overall level of satb1 within the cell. 21743493_4 together, these findings suggest that foxp3 acts to negatively regulate satb1 levels both directly, through repression of satb1 transcription, and indirectly through the induction of mir-7 and mir-155 that then target the 3'-utr of the satb1 mrna. 18399940_1 the identifiction of the ompx regulator was by systematically inactivation the salmonella homologues of conserved e. coli enterobacteria srna genes, and compared the ompx levels of the resulting mutants with those of wild-type and hfq mutated salmonella. 18399940_2 only cyar was pursued as the candidate srna responsible for negative regulation of ompx synthesis.then, 23108868_1 upregulationof dnmt1 as a result of mir-152 downregulation has been observed during hcc development. 23108868_2 mir-152 may participate in hbv-induced epigenetic modifications through dnmt1. 26812313_1 here, we validated scd-1 as the target of mir-125b using a dual luciferase assay. 26812313_2 this study indicated that mir-125b regulates lipogenesis by targeting scd-1; therefore, mir-125b might be applied in therapy of lipid metabolism disorders. 26812313_3 herein, we showed that mir-125b could inhibit scd-1 expression by targeting the 3- -untranslated region of its mrna, thus affecting lipogenesis and fat composition of porcine adipocytes. 26812313_4 thus, scd-1 was confirmed as the target of mir-125b. 26812313_5 our luciferase assay results showed significantly decreased luciferase activity of pgl3-scd-1 3'-utr versus control, with no changes of pgl3-scd-1 3'-utr-mut and pgl3-scd-1 3'-utr-del, which proved that mir-125b may act on scd-1 by targeting seed sequence in the 3'-utr. 20089965_2 recent studies identified microrna-34a as a major downstream target of p53. 21867514_1 cdyl and rcor3 are also target of mir-141-200c cluster. 21867514_2 interestingly, several essential components of the ctbp/zeb complex, namely zeb1/2, ctbp2, rcor3 and cdyl , are predicted target of the mir-141-200c cluster. 21867514_3 ctbp2 has one mir-141 targetsite and one mir-200c targetsite, while zeb1 and cdyl have two mir-200c targetsites. 21867514_4 rcor3 has one mir-141 targetsite. 21867514_5 although the expression of cdyl and rcor3 is less obviously affected by overexpression of mir-141 and mir-200c in panc-1 cells as compared to ctbp2 and zeb1 , we observed a downregulation of cdyl and rcor3 on the protein level, when mir-141 or mir-200c were transiently transfected in panc-1 cells ,4d, suggesting that cdyl and rcor3 are also target of the mir141-200c cluster. 26553359_1 these observations demonstrate that mir-198 binds directly to the 3- utr of shmt1mrna, negatively regulating shmt1 expression. 26553359_2 mir-198 suppresses cell proliferation, enhances cell apoptosis, and causes cell-cycle arrest in lung adenocarcinoma by directly targeting shmt1. 26359029_1 piglets born to betaine-supplemented sows demonstrated a significant up-regulation in the hepatic expression of mir-124a and mir-4334-5p , which is predicted to target stat3. 26359029_2 five binding sites of mir-124a and 3 binding sites of mir-4334-5p were predicted to target 3'-utr of porcine stat3 with an online mirna prediction tool. 19082544_1 such a study revealed that this mirna-induced knockdown of aatf gene, within normal human blood mononuclear cells, was responsible for the suppression of genes coding for bcl-2, c-myc, par-4 and dicer. 21915288_1 luciferase assayand transfection confirmed mir-143 binding to 3' utr of prostaglandin-endoperoxidase synthase 2 mrna and mir-143 regulation of ptgs2 in amcs. 21915288_2 figure 3mir-143 binding to the 3- utr of ptgs2 mrna. 21915288_3 ptgs2 mrna expression levels, however, in both aecs and amcs were not significantly changed by mir-143 transfection. 21915288_4 these results suggested that mir-143 regulation of ptgs2 expression occurs largely by translational inhibition than by ptgs2 mrna degradation in the amnion, particularly in amcs. 25034398_1 the activity of mcl-1 3'-utr reporter was inhibited by co-transfection with mir-193b mimic. 22324810_1 micf inhibits lrp synthesis by an antisense mechanism that involves direct base-pairing to the lrp mrna. 26163618_2 up-regulation of mir-99a would markedly reduce the expression of mtor and its downstream phosphorylated proteins . 26163618_3 similar to restoring mir-99a expression, mtor down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mtor expression significantly reversed the mir-99a antitumor activity and the inhibition of mtor/p-4e-bp1/p-s6k1 signal pathway profile. in clinical specimens and cell lines, mtor was commonly overexpressed and its protein levels were statistically inversely correlated with mir-99a expression. 9230301_1 genetic screens of randomly inserted lacz translational fusion experiment shows that yhiv is repressed by oxys. 9230301_2 oxys repression of yhiv is partially sigmas-dependent. 26782975_1 these results indicated that mirna-378 affected bmp4 expression at the mrna as well as the protein level. 26782975_2 the results showed that inmirna-378-transfected cells, the luciferase activity of the bmp4 3'-utr-driven vector was reduced by ~60% compared with that in the negative control-transfected group; however,luciferase activity of the mutant luciferase reporter vector for bmp4 was not affected by mirna-378 . 26782975_3 this result confirmed that bmp4 is a direct target of mirna-378. 26782975_4 this indicates that the downregulation of bmp4 mimics the function of mirna-378 on myogenic differentiation of c2c12 cells, further indicating that mirna-378 regulates myogenic differentiation by downregulating bmp4. 26622903_1 these data demonstrated that mir- 195 inhibits the expression of ccnd2 and myb in hela cells. 26622903_2 the results showed that mir- 195, but not the nc, specifically decreased the luciferase levels from the reporters , suggesting that mir- 195 regulates the expression of ccnd2 and myb directly. 26622903_3 the present study demonstrated that mir-195 directly targeted the 3'-utr of the myb gene and inhibited its expression in hela cells, suggesting that the deregulation of mir-195-mediated myb inhibition may serve as a general mechanism in the development of a variety of cancers . 20947829_1 using in vitro and in vivo approaches, we demonstrate that mir-218 directly represses the expression of robo1, robo2, and glucuronyl c5-epimerase , and that an intact mir-218-slit-robo regulatory network is essential for normal vascularization of the retina. 20947829_2 we identified mir-218-1 and mir-218-2 within intron 14 of the mouseslit2 and slit3 genes, respectively . 20947829_3 the activity of the luciferase reporter linked to the robo1, robo2, and glce 3'-utrs, normalized to -beta-galactosidase activity, displayed dose-dependent repression by mir-218 . 20947829_4 furthermore, our results suggest that robo1/2 and glce positively influence the migration rate of ec cells in culture and that mir-218 counteracts this process. 20947829_5 importantly, the mrna and protein levels of robo1, robo2, and glce were enhanced by mir-218 knockdown in the retina , although robo2 mrna levels were not significantly affected by mir-218 knockdown . 20947829_6 quantification of western band intensity confirmed the significant enrichment of robo1, robo2, and glce protein levels on silencing of mir-218 . 23543060_1 based on computational analyses revealing 2 mir-26-binding sites in the 3- utr of kcnj2 , we conducted western blot analysis and luciferase reporter gene assays to experimentally clarify whether kcnj2 is in fact a target for mir-26. 23543060_2 these results are consistent with computational predictions excluding these genes as targets for mir-26 and indicate that the effect of mir-26 on kcnj2/kir2.1/ik1 is target specific. 22307404_1 to confirm that the decrease in the luciferase activity was indeed due to the direct binding of mir-125b to arid3b 3'-utr, c1-mut construct was generated. 22307404_5 no significant decrease in cell proliferation was noted in arid3b silenced cells compared to arid3b expressing mcf7 , indicating that mir-125b targeting of arid3b was important for cell migration behavior changes. 21668589_2 this raises a possibility that the down-regulation of mir126 triggers the upregulation of spred1. 21668589_5 these results strongly support our hypothesis that mir126 regulates fcepsilonri-mediated cytokine production by directly targeting spred1 in mast cells. 26458304_1 the publicly available programs diana lab , miranda targetscan and pictar have been indicated mir-219-5p potential targets pdgfralpha. 26458304_2 mir-219-5p mimics had no effect on the luciferase activity of the pmir-pdgfralpha-mut construct containing the mutated putative mir-219-5p binding sequence in the 3'-utr of pdgfralpha mrna . 26458304_3 these data suggest that pdgfralpha is one of the direct targets of mir-219-5p. 26458304_4 the increased endogenous mir-219-5p levels were associated with significantly decreased endogenous pdgfralpha mrna and protein expression. 26458304_5 transfection with 150 pmol of mir-219-5p inhibitor showed a decrease of mir-219-5p expression and an increase pdgfralpha mrna and protein expression compared with the inhibitor control. 23085654_1 in this study, we found that the expression of ghr mrna and protein was regulated by transfected bta-mir-15a synthetics. 23085654_2 the lactogenic activity of gh may be elicited directly through the activation of stat5 followed by the activation of milk protein gene transcription in alveolar cells , so we suggest that the operative mechanism was that mir-15a deregulated ghr, affected jak2-stat5 signal pathway and decreased the expression of -beta-casein. 23085654_4 the present study showed that bta-mir-15a negatively regulated the expression of ghr, confirming the prediction by bioinformatics that the ghr gene could be a potential target of bta-mir-15a. 26825552_1 these evidences suggest that mir-10 regulate human ecs behavior through targeting mib1 as well. 20813046_1 here we showed that mir-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene puma in human glioma cells. 20813046_2 enforced expression of mir-22/222 induced cell survival whereas knockdown of mir-221/222 rendered cells to apoptosis. 18246122_1 mir-221 and -222 target the 3'-utr of kit and p27 mrnas, but interfere with trail signaling mainly through p27 . 21152115_1 ebv mir-bart5 inhibits the expression of the cellular protein puma to promote host cell survival and the establishment of latent ebv in-fection. 23569431_1 mechanistically, we found that overexpression of mir-34a led to decreased eag1 expression in osteosarcoma cells while inhibition of mir-34a increased eag1 expression. 23569431_2 taken together, our results suggest that mir-34a could inhibit osteosarcoma growth via the down regulation of eag1 expression. 23569431_3 these results suggest that the tumor suppressor activity of mir-34a is mediated through negative regulation of oncogenic protein eag1. 25084986_1 mir-31, mir-93, mir-146a, and mir-199a suppressed luciferase activity significantly. 25084986_2 these results indicate that mir-31, mir-93, mir-146a, and mir-199a target the 3'-utr of glut4, leading to the change of firefly luciferase translation. 25084986_3 mir-31, mir-94, mir-146a and mir-199a repress the glut4 expression by targeting 3'-utr. 23663545_1 interestingly,we demonstrated that mir-141, which was more highly induced by h5n1 than by h1n1 , had an ability to suppress the expression of a cytokine - transforming growth factor -beta2.since tgf-beta2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza h1n1 could induce a persistent expression of tgf-beta2, we speculate that the modulation of tgf-beta2 expression by different influenza subtypes via mir-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression. 26265044_2 the result of a dual-luciferase activity assay using the 3 ' utr of apaf-1 also indicated that mir-17 significantly decreased the expression of luciferase, demonstrating that mir-17 targets the 3 ' utr of apaf-1 . 19721136_1 real time pcr array for ratapoptotic genes, computational targetgene analyses, and luciferase reporter assay identified flice-associated huge protein /caspase-8-associated protein-2 in mscs as the targetgene of mir-210. 19721136_2 our in silico search resulted in a consensus putative targetsite of mir-210 relevant to apoptosis in the 3'-utr of casp8ap2 mrnas . 19721136_3 these results clearly showed that flash/casp8ap2 plays an important role in apoptosis as a downstream target of hypoxia-induced mir-210 during ip of mscs. 26253263_1 map3k4 and map3k9 are the direct targets of mir-148a. 26253263_2 mir-148a down-regulates map3k4 and map3k9 expression 21305018_1 here we show a striking up-regulation of mir-29 and mir-15 family mirnas during murineaortic development withcommensurate down-regulation of target including elastin and other extracellularmatrix genes. 21305018_2 these results confirm previous observations that the 3- utr of murineeln is a mir-29 target and additionally show that the multiple mir-29 mres act synergistically . 21305018_3 the second construct additionally contained four mir-29 mres, and was significantly responsive to both mirna precursors, indicating a specific effect of mir-15 and mir-29 mres in the cds of murineeln. 21305018_4 in addition, col1a2 has neither mir-15 nor mir-29 mres in its 3- utr and was responsive to both mir mimics. 21305018_5 although col1a1 has one mir-15 and one mir-29 mre in its 3- utr, the great majority of mres for these mirnas are located in its cds. 24183204_1 we found that mir-184 expression was significantly high in hcc tissues, but inppl1 expression was obviously low. 24183204_2 subsequently, inppl1 was identified as a target of mirna-184 by bioinformatics and dual luciferase assay. 24183204_3 additionally, we also proved that mir-184 silencing inhibited cellular proliferation by over expressing inppl1 and induced hepg2 apoptosis by caspase 3/7. 25620172_1 overexpression of mir-133a inhibits cell growth and invasion and induces cell apoptosis and cycle arrest through repressing tagln2 gene, suggesting that mir-133a might be used as a biomarker or therapeutic target for the treatment of gastric cancer. 26635599_2 in our study, we find both mir-99b-5p and mir-100-5p affect neuron survival by targeting mtor. 26635599_3 the inverse-correlated expression profile of mir-99b-5p/mir-100-5p and mtor also indicates that mirnas-regulated mtor pathway may play different roles during the progression of brain injuries induced by a-beta deposition. 26833707_1 mir-708 could directly target the lsd1 3'utr to downregulate the expression. 26833707_2 further studies suggested that inhibition of lsd1 could phenocopied function of the mir-708 overexpression in mda-mb-231 cells .overexpression of lsd1 could counteract the effects of mir-708 on the proliferation and invasion. 21285944_1 here, for the first time, we demonstrate that mir-93 and its family members directly target tgf--beta receptor ii to enhance ipsc generation. 21285944_2 to determine whether mouse tgfbr2 and p21 are targeted by mir- 93 and mir- 106b, mir mimics were transfected into mefs and total cell lysates were analysed by western blotting 48 h later. 21285944_3 indeed, mir- 93 and mir- 106b expression efficiently decreased both tgfbr2 and p21 protein levels and p21 mrna levels were decreased by ~5- 30% while tgfbr2 was decreased by ~60- 70% . 21285944_4 figure 5.mir- 93 and mir- 106b directly target mouse p21 and tgfbr2. 21285944_5 tgf-beta receptor ii was also overexpressed in mefs, and ips enhancement by mir- 106b was compromised under such condition . 21285944_6 altogether, our data identify that tgfbr2 and p21 are the direct target of mir- 93 and mir- 106b and down regulation of these genes can enhance the reprogramming process. 21285944_7 these mirnas enhanced reprogramming in a manner similar to that seen with the mir- 106b ~25 clusters , and transfection of these mirs resulted in decreased tgfbr2 and p21 protein levels as well as tgfbr2 mrna . 25458897_1 these results thus suggested a negative correlation between acvr2a and mir-590-3p/5p during the differentiation of mescs. 25458897_2 these results demonstrated that mir-590 inhibits the activin signaling pathway by directly targeting acvr2a. 25458897_3 these results showed that mir-590 regulated the dna damage repair and cell proliferation of mescs through directly targeting acvr2a. 20424141_2 sirt1 has been reported to have a mir-34a binding site within its 3'-untranslated region . 14617150_1 when ryhb and sodb mrna were added in vitro, translation of sodb mrna was greatly diminished. 14617150_2 ryhb binding to the ribosome binding site of sodb mrna followed by translational inhibition could explain this result. 14617150_3 as shown, ryhb basepairing to the rbs of sodb mrna could potentially prevent ribosome biding. 14617150_4 the complementarity between bases -2, -3 and -6 of sodb mrna and bases 44, 45 and 49 of ryhb seems to be essential for their interaction. 14617150_5 it should be noted that this regulatory cascade does not entail a direct action of hfq on sodb mrna. 22484120_1 gsk-3-beta messenger rna was identified as a direct target of mir-26a by computational analysis and experimental assays. 22484120_2 mir-26a-mediated reduction of gsk-3-beta resulted in activation of -beta-catenin and induction of several downstream genes including c-myc, cyclind1, and peroxisome proliferator-activated receptor -beta. 22484120_3 this approach led us to identify mir-26a as a noncoding rna that directly binds the 3- -untranslated region of the gsk-3-beta mrna. 22484120_4 these results demonstrate that gsk-3-beta is a direct target of mir-26a. 22484120_5 our findings are consistent with a recent study by mohamed et al showing that mir-26a target gsk-3-beta in human airway smooth muscle cells. 26396496_1 dual-luciferase reporter assay showed that mir-133b interacted with the 3'-untranslated region of gst-π. 26396496_2 compared to controls, the mrna and protein levels of mdr1 and gst-π were downregulated after mir-133b transfection and upregulated after anti-mir-133b transfection. 26396496_3 these results indicate that mir-133b directly binds to the 3'-utr of wild type gst-π. 20435894_1 this inhibitory effect of il-10 on mir-155 led to an increase in the expression of the mir-155 target ship1. 20435894_2 the fact that lps potently induces mature mir-155 suggests that as mir-155 expression increases, its ability to bindto the 3'-utr of ship1 should result in a decrease of ship1 mrna expression. 24958806_3 furthermore, we demonstrate that mir216a exerts its role by directly targeting eif4b and zeb1. 25594002_2 up-regulation of mir-34a was correlated with down-regulation of its target e2f3 and up-regulation of p53. 26919700_1 irs-2 was one of the targets of mir-126. 26919700_2 mir-126 inhibited the -beta-cell proliferation through irs-2 instead of irs-1. 26919700_3 mir-126 may take part in the glucose homeostasis both through its target irs-2 and irs-1. 26919700_4 this result demonstrated that the three nucleotides uac was crucial for the binding of mir-126 with the irs-2. 26919700_5 in general, the above results indicated that irs-2 was one of the target genes of mir-126. 26919700_6 together with the up-regulation wave of the endogenous mir-126, the expression of irs-2 and irs-1 mrna displayed a different mode of changes. 20066053_1 we found that, in both cortical precursors and their neuronal progenies, emx2 antisense rna contributes to post-transcriptional down-regulation of its sense partner, possibly by a dicer-promoted mechanism.interestingly, 20066053_3 remarkably, knock-down of emx2os induced by mir-alphaemx2os-774 rescued the emx2-mrna decrease to large extent , suggesting that emx2os-ncrna substantially contributes to emx2 down-regulation at the time when cp neurons are born. 26791102_1 first, mir-214 directly targeted atf4, a crucial transcriptional factor involved in anti-stress responses, down regulation of mir-214 releases the repression of atf4 translation and leads to increased atf4 protein content. 26791102_2 all considered, these data support a direct regulation of atf4 by mir-214 through a posttranscriptional mechanism at its 3'-utr. 26791102_3 we here presented a novel function of mir-214 in protecting cells from oxidative stress-associated cell death through interlinking nrf2 and atf4, ezh2/bim signaling in erythroid cells. 24356076_2 several micrornas, including let-7d and mir-766, were dysregulated in apl cells treated with as2o3.the 24356076_3 expression of caspase-3 and bax, which are targets of let-7d and mir-766, respectively, were up-regulated in as2o3 treated cells. 25875420_2 using a luciferase assay, we found that mir-138-5p directly targets foxc1. 25875420_3 inaddition, we found that exogenous over-expression of mir-138-5p inhibits pancreatic cancer cell growth, both in vitro and in vivo, and that sirna-mediated silencing of foxc1, a direct target of mir-138-5p, similarly inhibits pancreatic cancer cell growth. 25875420_4 to test this hypothesis, we used a luciferase assay and, by doing so, confirmed that mir-138-5p indeed directly targets foxc1 . 26285119_1 meanwhile, we also demonstrated that gm-csf was a main inducer of mir-200c in tumor environment, and mir-200c in turn promoted the expansion and immune suppressive activity of mdscs via targeting phosphatase and tensin homolog and friend of gata 2 , which can lead to stat3 and pi3k/akt activation. 26285119_2 here we show that mir-200c, whose genomic locus is located in fragile regions within two chromosomal clusters, including mir-200c-141 cluster and mir-200b-200a-429 cluster, strongly promotes the suppressive potential of mdscs via targeting pten and fog2, leading to subsequent stat3 and pi3k/akt activation. 26285119_3 importantly, the mutation in the putative mir-200c binding sites abolished the repression by mir-200c, demonstrating that mir-200c could specifically target their binding sites in the 3'-utr of pten. 26285119_4 taken together, these data demonstrate that mir-200c targets and reduces the levels of pten and fog2 in mdscs. 23393589_1 these data support the notion that over-expression of mir-130a/301a/454 leads to smad4 down-regulation, thus inhibiting tgf--beta signaling-mediated cell growth suppression, which contributes to the development of colon cancer. 23393589_2 these results further demonstrated that the growth-promoting roles of mir-130a/301a/454 were mainly through inhibition of smad4 expression. 25095979_1 in western blot and luciferase assays, hmgb3 was identified as a major target of mir-513b. 25095979_2 moreover, we also found that the expression of hmgb3 lacking in 3' utr could abrogate the anti-migration and pro-apoptosis function of mir-513b. 25095979_3 these findings suggest the importance of mir-513b targeting of hmgb3 in the regulation of growth, migration and apoptosis of gc, improve our understanding of the mechanisms of gc pathogenesis, and may promote the development of novel targeted therapies. 25910896_1 bcl2 is a target of mir34a in idd and mir-34a repressed expression of bcl-2. 25910896_2 transfection of the mutant bcl2 3'-utr with the same constructs had no effect on luciferase activity, confirming that bcl2 is a direct target of mir34a. 20103531_1 these results showed a slight reduction in pten expression when mir-205 was overexpressed as compared with the luciferase shrna control vector . 20103531_4 as in the western blot analysis, when mir-205 was overexpressed, pten mrna levels decreased by approximately 50% as compared with the luciferase shrna control . 20103531_5 collectively, these results indicate that mir-205 regulates pten expression. 20103531_6 mir-205 target the mrna of the tumor-suppressor protein pten. 26825461_1 we inhibited mir-142- 5p and mir-143 in thp-1 cells using antagomir oligonucleotides and measured the expression of six pyrogens: il6st, ifna1, tnf, tlr2, il6 and pge2 by rt-qpcr .4d. of these, three targets il6, ifna1 and pge2, were expressed at levels below the detection limit of rt-qpcr pre- and post-knockdown of either mirna. 26825461_2 we confirmed that mir-142- 5p and mir-143 regulated the expression of il6st and tlr2 respectively .4d. 20727858_1 important antiapoptotic bcl-2 was identified to be directly targeted by mir-195, and mir-195 was further suggested to exert its proapoptotic function mainly through targeting bcl-2 expression. 26313916_2 taken together, these experiments provided clear and strong evidence that mir-26a acted as a physiological regulator in mouse adult sensory neurons to maintain gsk3-beta at a lower level. 26313916_3 taken together, these results indicated that gsk3-beta was the major target of mir-26a in adult mouse sensory neurons that functioned to control axon regeneration. 26313916_4 therefore, the result here suggests that mir-26a control axon regeneration via gsk3-beta by targeting gene expression at the neuronal soma. 20388802_1 mir-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein ped. 26497687_1 we identified 54 mir-155-specific target genes in bl cells and confirmed mir-155 targeting of det1, niam, trim32, homez, psip1 and jarid6. 23727126_1 qrt-pcr analysis of the livers from these animals after one week of treatment showed a significantly increased mir-122 level of 36759 copies per 1ng total rna with concomitant decrease in the protein levels of two of its validated targets namely, adam10 and mapre1 . 26758252_1 studies from both in vitro and in vivo shown that mir-24 regulates bcl2l11 expression by directly binding with 3'-utr of mrna, thus promoting cell growth, migration while inhibiting cell apoptosis. 26758252_2 the subsequent luciferase assay showed that bcl2l11 is a direct target of mir-24; overexpression of mir-24 in gc cells leads to the inhibition of bcl2l11, thus promoting cell proliferation, migration while reducing cell apoptosis. 26758252_3 these data demonstrated that mir-24 is an important regulator of bcl2l11 in gc cells, and mir-24 regulates bcl2l11 expression by directly targeting the 3'-utr of bcl2l11 mrna. 20232393_1 ectopic transfection of mir-138 reduced the expression of both rhoc and rock2 in tscc cells. 20232393_2 these results suggested that mir-138 regulates rhoc gene expression, at least in part, by regulating the stability of rhoc mrna. 20232393_3 furthermore, as shown in figure 2c, ectopic transfection of mir-138 reduced the protein level of rhoc in um1 cells, and knockdown of mir-138 using anti-mir-138 pna increased the protein level of rhoc in um2 cells. 20232393_4 as illustrated in figure 4, our results suggest a novel paradigm in which mir-138 regulates rhoc-specific gtpase signaling cascade by targeting both rhoc and rock2 mrnas concurrently and suppresses their expression at posttranscriptional levels. 22028919_1 both mir-101 and mir-494 synthetic mimics significantly inhibited the expression of a reporter construct containing the 3'-utr of cftr in luciferase assays. 22028919_2 thus, mir-101 and mir-494 functionally interact with the cftr 3'-utr and suppress the corresponding protein product. 22664106_1 up-regulation of mir-26a promotes apoptosis of hypoxic ratneonatal cardiomyocytes by repressing gsk-3-beta protein expression. 22664106_2 we identified gsk3b as a direct downstream target of mir-26a. 22664106_3 to test whether gsk-3-beta is a mir-26a targetgene in cardiomyocytes, we have confirmed that h2o2 decreases gsk-3-beta expression in cultured cardiomyocytes and . 22664106_4 mir-26a is able to bindto gsk-3-beta and regulate its expression directly using a construct in which a fragment of the 3 its exprgsk-3-beta mrna with the putative mir-26a binding sequence. 22664106_5 this result indicates that gsk-3-beta is indeed a functional targetgene of mir-26a that is involved in mir-26a-mediated pro-apoptotic effect on cardiomyocyte injury elicited by h2o2. 22664106_6 for this reason, we suggest that mir-26a induced apoptosis in h2o2-stimulated cardiomyocytes by post-transcriptional regulation of gsk-3-beta. 26805687_1 gas1 was a direct target gene of mir-184. 26805687_2 overexpression of mir-184 inhibited the gas1 protein expression in np cells . 25241899_2 these data support that mir-141 directly and specifically regulates stat5a in breast cancer cells. 25241899_3 we demonstrate that stat5a is specifically targeted by mir-141 in breast cancer cells. 25241899_4 here we demonstrate mir-141 directly targets two transcription factors involved in regulating mammary cell differentiation: pr and stat5a. 23169640_1 interestingly, we found that mir-155 directly target hdac4, a corepressor partner of bcl6. 23169640_2 luciferase reporter assay confirmed a significant down-regulation of hdac4- 3'-utr by mir-155 mimic compared with scrambled control in multiple cell lines . 23169640_3 this interaction was abrogated when the mir-155 binding site in hdac4-3' utr was deleted or mutated , which confirmed that hdac4 is a direct target of mir-155. 23169640_4 altogether these results confirm that hdac4 is a bona fide target of mir-155. 8670904_1 dsra rna was found to regulate dsrb::lacz indirectly, by modulating rpos synthesis. 22962603_1 with an integrated target prediction tool , ctnnb1 was predicted to be a potential target of mir-214 by miranda, pita, rnahybrid and targetscan.to 22962603_2 validate ezh2 and ctnnb1 were indeed direct targets of mir-214, we tested the ability of mir-214 to recognize the 3'-utr of ezh2 and ctnnb1 mrna using a dual-luciferase reporter assay. 22962603_3 confirming that ezh2 and ctnnb1 were indeed direct downstream functional targets of mir-214 . 22291592_1 we identified an additional 2,972 cds mirna-interaction sites present in at least two libraries, 89.7% of which could be assigned to a mirna . 26204489_1 the levels of mir-26b in cov644 and ovcar-3 cells significantly increased after transfection with mir-26b mimics, as compared to cells transfected with a scramble mirna. 26204489_2 the binding sites of mir-26b in the kpna2 3'-utr are shown. 26204489_4 our findings strongly suggest that kpna2 expression is suppressed by mir-26b through directly binding. 26151666_1 these results indicate that mir-138 significantly suppressed the activity of wt but not mut pdk1 3'-utr in human asmcs. 26151666_2 overexpression of mir-138 significantly suppressed the mrna level of pdk1, while inhibition of mir-138 elevated the mrna level of pdk1 in human asmcs. 26151666_3 taken together, these results reveal that mir-138 could negatively regulate pdk1 expression through a partially complementary binding site in the 3'-utr of pdk1. 26144867_2 we concluded that ttp expression is reduced during neural differentiation and that this effect is at least in part mediated by mir-9. 20668208_2 it is plausible that chronic morphine exposure may increase the expression of let-7 which, in turn, down-regulates mor expression, contributing to the behavioral manifestation of opioid tolerance. 18940871_1 finally,we demonstrate that lmp1-mediated activation of mir-155 in an ebv-negative background correlates with reduction of protein pu.1, which is a possible mir targe. 26854065_1 in addition, the down-regulation of mir-200b in endometriosis is associated with a reduction on klf4 expression. 20881232_2 mir-631 inhibitor enhanced both sult1a1 mrna and protein levels in mcf7 and mcf10a cells . 20881232_3 thus, variant alleles in the sult1a1 3'-utr affect the binding ability of mir-631 to sult1a1 but not the abundance of mir-631 . 24257599_1 mir-bart16 also inhibited plsg-lmp1nt671 but not plsg-lmp1nt692, indicating that mir-bart16 targets the 5'region of the lmp1 3'utr. 19404929_1 when we tested the effect of mir-124a on cdk-2 expression by transfection of pre-mir-124a into primary ra fls and e11 cells, we found that overexpression of mir-124a substantially suppressed the expression of cdk-2 in both cell types . 19404929_2 as shown in figure 4d, mir-124a selectively suppressed the luciferase activity driven by the wild-type 3'-utr, but not the mutant form, of cdk-2 mrna, indicating that cdk-2 mrna is a direct target of mir-124a. 23857777_1 further analysis of mir-373 in vivo oncogenic function reveals that it is mediated through its negative regulation of tp53inp1, lats2 and cd44. 23857777_2 as shown in fig 5a and b, tp53inp1, lats2 and cd44 levels were significantly reduced in mia paca-2 cells transfected with pre-恗ir373; while all three proteins were increased in mia paca-2 cells transfected with anti-373, indicating a direct post-恡ranscriptional regulation of those three target genes by mir-373. in addition, this study provides a comprehensive mechanism for zip4-恗ediated pancreatic cancer growth involving creb-恉ependent transcription, enhancement of oncogenic mir-373 expression, and reduction in key mir-373 regulated targets, including the tumour suppressor genes tp53inp1, lats2 and cd44. 20018759_2 finally, in transfected hela and 293t cells, overexpression with vectors expressing mir-221. 20018759_3 the cyclin-dependent kinase inhibitor p27 and the tyrosine-kinase receptor c-kit have been identified as target of mir-221 and mir-222 . 26261543_1 moreover, we demonstrated that mir-218 directly binds to the 3'-utr of hmgb1 gene. 26261543_3 these data suggested that mir-218 could directly target the 3'-utr sequences of hmgb1. 26261543_4 these results agree with the fact that mir-22 regulates hmgb1 by targeting the 3'-utr of it and suppressing its translation. 26261543_5 in conclusion, our results revealed that hmgb1 was directly targeted by mir-218, and overexpressed mir-218 could suppress the hmgb1 level, and block the hmgb1-mediated autophagy in drug-treated ec cells. 21750350_1 fancg is the mir-23a targetgene. 21750350_2 to determine whether mir-23a affected the expression of the fancg gene, we performed immunoblotting analysis and found that the fancg protein was considerably decreased in the ectopic expression of pre-mir-23a, following ane exposure . in contrast, knockdown of mir-23a restored expression of the fancg protein following ane exposure . 21750350_3 similar results were also seen where fancg mrna levels were repressed by mir-23a . 21068409_2 the results reveal that transfection of mir-101 mimic but not control dsrna markedly inhibits the production of mkp-1 protein . 21068409_4 mir-101 represses mkp-1 expression through interaction with the 3- utr of mkp-1. 21068409_5 transfection with mir-101 mimics markedly inhibited the luciferase activity for the wild-type 3- utr of mkp-1 but showed no repression effect for the mutated 3- utr of mkp-1 when compared with that for the control dsrna , suggesting that mir-101 may repress mkp-1 expression by binding to the 3- utr of mkp-1 in a direct and sequence-specific manner. 21068409_6 these results suggest that mir-101 may regulate the lps-induced activation of jnk or p38 through targeting mkp-1. 21068409_7 these results indicate that mir-101 can be induced by different tlr ligands and may play a role in the innate immune responses to microbial infection through targeting mkp-1. 23201159_1 these results suggest that mir-145 regulates downstream molecules via targeting n-ras and irs1. 23201159_3 these results indicate that mir-145 inhibits vegf transcriptional activation through targeting both n-ras and irs1 that are functional. 23201159_4 meanwhile, the activation of akt and erk1/2 signaling pathways and the expression of hif-1alpha were significantly suppressed by mir-145 . 23201159_5 vegf, the downstream target of akt and erk1/2, was also inhibited by mir-145 overexpression when compared to negative control , demonstrating that in an animal model, mir-145 can inhibit akt and erk1/2 activation by targeting n-ras and irs1, thus suppressing the downstream molecules hif-1 and vegf, which are involved in tumor angiogenesis and tumor growth. 20657750_3 therefore, it appears that mir-29b does not affect mmp-2 mrna expression. 20657750_4 mir-29b target matrix metallopeptidase-2 and represses pro-mmp-2 protein expression. 21946562_1 interestingly, among the already experimentally confirmed targets of the mir-34 family is the sirt1 mrna , that has two binding sites of mir-34c . 21946562_2 as shown by the respective luciferase assays in supplementary figure s4d, targeting of sirt1 mrna by mir-34c applies also to neuronal cells. 21946562_3 administration of mir-34c sirt1 target protector was able to rescue mir-34c mimic-mediated learning impairment and resulted in increased sirt1 protein levels , thus confirming that action of mir-34c on sirt1 protein in vivo is direct and based on mir-34c/mrna interaction. 21946562_4 mir-34c induced impairment of associative learning corresponded with reduced sirt1 levels , confirming successful incorporation of mir-34c mimic into the risc complex and specific translational repression of target mrnas. 21946562_5 furthermore, specific blocking of the interaction between mir-34c and its sirt1 3'-utr binding sites through mirna target protectors was able to reverse the above effects. 26700675_1 importantly, we identified that the 3- -untranslated region of itga2 was a direct target of mir-128. 26700675_2 we report that overexpression of mir-128 can inhibit epithelial-mesenchymal transition and identify a new target integrin alpha2 . 26700675_3 collectively, these results reveal the negative regulatory role of mir-128 to itga2 in mg-63 cells. in addition, we identified itga2 as a direct target gene of mir-128, suggesting that mir-128 played a suppressor role in osteosarcoma tumorigenesis. 19158788_1 thbs1 mrna was downregulated in cells engineered to express kshv mirnas and also showed that thbs1 translation is inhibited by several kshv mirnas, in particular by mir-k12-6-3p, which shows mirna seed complementarity to two sites in the thbs1 mrna 3'utr. . 17881434_1 we observed a significant inhibition of luciferase from reporters containing the 3'utrs of ldoc1, matr3, and tm6sf1 in the presence of mir-155 or mir-k12-11. in contrast, neither mirna had any effect on the phf17 or nfat2cip 3'utrs. 17881434_2 thus, these assays confirmed ldoc1, matr3, and tm6sf1 as being targets of both mir-155 and mir-k12-11. 19585654_1 here, using a global microarray-based mirna profiling approach followed by validation with quantitative reverse transcription polymerase chain reaction, we have demonstrated that conserved mir-181 family members were up-regulated in epcam afp hccs and in epcam hcc cells isolated from afp tumors. 19585654_3 importantly, inhibition of mir-181 led to a reduction in epcam hcc cell quantity and tumor initiating ability, whereas exogenous mir-181 expression in hcc cells resulted in an enrichment of epcam hcc cells. 19585654_5 taken together, our results define a novel regulatory link between mir-181s and human epcam liver cancer stem/progenitor cells and imply that molecular targeting of mir-181 may eradicate hcc. 23829529_1 the first example includes a nat complementary to zeb2 mrna and its expression promotes the retention of a large intron at the 5- -end of the sense transcript. 19302977_1 it has been reported that mir-21 could post-transcriptionally downregulate tumor suppressor pdcd4 and tpm1 and stimulates invasion and metastasis in colorectal cancer and breast cancer cells. 19302977_2 so we checked whether these two mir-21 target were regulated by mir-21 in prostate cancer cells. 19302977_4 s2, antimir-21 significantly increased the pdcd4 and tpm1 protein levels in a dose-dependent manner. 26634745_1 bioinformatics analyses showed that mir-4262 targeted the 3'-utr of opn mrna to inhibit its translation, which was proved by luciferase reporter assay. 21611182_1 to determine whether genes identified in pc12 cells also were regulated by mir-132 knockdown in vivo, we used il-6 as a test case because of its involvement in nervous system function . 21829663_1 for example, mir-23a and -125a up-regulation as well as mir-19a/b down-regulation by both hbx forms were verified.the 21753737_1 figure 4a illustrates the approximate binding sites of mir-132 and mir-21 within the -beta2-subunit 3'-utr region. 21753737_2 subsequent luciferase reporter gene assays indicated that mir-21, mir-132, and mir-222 significantly repressed luciferase activity , whereas mir-31 and mir-214 had no effect . 21753737_4 a, mir-132 and mir-21 seed sites within the cacnb2 3'-utr are shown. 19188590_1 mir-182 over-expression promotes migration and survival by directly repressing microphthalmia-associated transcription factor-m and foxo3. 19188590_2 further evidence that endogenous mir-182 actively blocks foxo3 and mitf in melanoma cells came from our observation that transfection of anti-mir-182 oligonucleotides results in foxo3 and mitf up-regulation . 19188590_3 finally, concomitant over-expression of mir-182 and either foxo3 or mitf-m abolished the stimulatory effect of mir-182 on the invasive capacity of melanoma cells , demonstrating that foxo3 and mitf repression are necessary effectors of mir-182. 20439467_1 mir-340 interacts with two of its targetsites on the 3'-utr of mitf mrna,causing mrna degradation and decreased expression and activity of mitf. 20439467_2 moreover, inhibition of mir-340 function in 451lu cells also increased the mitf protein level . 20439467_3 these data demonstrated that mitf mrna with short 3'-utr is regulated by mir-340. 20439467_4 together these data suggested that mir-340 acts through its targetsites on 3'-utr of mitf mrna, leading to its destabilization. 23576572_1 foxm1 was directly downregulated by mir-370 in gastric cell lines. 23576572_4 next, we validated foxm1 as a target of mir-370 by dual luciferase report assay. 23576572_5 thus, mir-370 directly targeted the binding site located at foxm1 3' utr and foxm1 may be a direct target of mir-370. 23576572_7 pylori and its key virulent factor caga induced the expression of foxm1 by inhibiting that of hsa-mir-370, which directly targeted foxm1, resulting in cell proliferation for gastric carcinogenesis by reducing p27 kip1 promoter activity and its expression . 20861672_1 mir-34c and mir-31 are associated with oxidative stress or activation of the hypoxic response/hif1a, which is sufficient to drive authophagy/mitophagy. 24078004_2 overexpression of reck could significantly reverse the oncogenic effect of mir-25. 24078004_3 taken together, mir-25 might promote gc cells growth and motility partially by targeting reck. 26765931_1 this technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting gsk-3b to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based mirna therapy for tissue engineering. 26765931_2 taken together, these results demonstrate that mir-26a upregulates ob activity through functionally targeting gsk-3b. 26765931_3 mechanistically, we find that osteogenic action of mir-26a is through functionally targeting gsk-3b to increase the ob activity rather than to suppress osteoclast activity 17848513_1 here, we show that two mirnas, mmu-mir-101a and mmu-mir-199a*, are spatiotemporally expressed in the mouse uterus during implantation coincident with expression of cyclooxygenase-2, a gene critical for implantation. 17848513_2 because mir-101a and mir-199a* expression overlaps with cox-2 in the pregnant mouse uterus, we assumed that cox-2 mrna expression is posttranscriptionally regulated by these mirnas. 17848513_3 we used two independent gain-of-function and a loss-of-function strategy to show that mir-101a and mir-199a* repress cox-2 translation. 17848513_4 these results show that both mir-101a and mir-199a* interact with the 3'utr of mcox-2 mrna in vitro, leading to its translational repression. 17848513_5 this result provides further evidence that cox-2 mrna is posttranscriptionally controlled by mir-101a and mir-199a*. 22983985_1 based on these results, we wanted to determine what effect akba treatment in these crc cell lines had on direct or downstream targets of the let-7 and mir-200 family of mirnas. 22983985_2 we chose to measure the effect of akba on cdk6, e-cadherin and vimentin, all downstream targets of the let-7 and mir-200 families of mirnas. 22983985_3 levels of cdk6 mrna expression were significantly reduced in all cell lines by treatment with akba, whereas levels of e-cadherin were significantly increased in hct116 and ht29 cells . 22983985_4 taken together, we interpret these results to indicate that akba induced up-regulation of the let-7 and mir-200 mirnas, as manifested by subsequent modulation of the expression of their target genes, to impact crc cell growth and metastasis. 26773497_1 suggesting that mir-328 targeted the plce1 by binding to plce1 3'utr sequence. 26773497_2 our results indicate that plce1 expression was significantly downregulated by mir-328 overexpression and upregulated when mir-328 expression was silenced 17996649_1 mir-223 is a direct transcriptional target of aml1/eto which induces heterochromatic silencing of mir-223.the 20377629_2 sirna-mediated inhibition of prins gene resulted in altered cell morphology and gene expression alterations, as demonstrated in a microarray experiment. in our silencing experiments, the gene-specific knocking down of prins expression resulted in a substantial downregulation of g1p3 expression, indicating that g1p3 may be one of the protein-coding genes that are under the control of prins. 26345908_1 similarly, the regulation of mir-375 on bmpr2 was mediated by the interaction between the tttgttc sequence in mir-375 and the gaacaaa sequence in bmpr2. 26345908_2 the results showed that ptgfrn and bmpr2 were the target genes of mir-7 and mir-375, respectively. 26345908_3 in the current study, ptgfrn and bmpr2 were identified to be the target genes of mir-7 and mir-375 based on the results of the in vitro dual-luciferase assay. 26523989_1 mir-185 modulates ldlr expression and ldl uptake by direct binding to ldlr mrna 3'utr. 19487542_1 interestingly, we also identified sod2 as another direct hsa-mir-222 target gene, and a potential targeting site was identified in the 3'-utr of the sod2 mrna . 19487542_2 take together, these results suggest that hsa-mir-222 regulates um1 cell invasion, at least in part, by indirectly regulating mmp1 expression through targeting sod2 mrna. 26711345_1 taken together, these data suggest that axon-enriched mir-181d specifically targets map1b and calm1 in drg neurons. 26711345_2 the present study substantially expands our understanding of the molecular mechanisms of fmrp functions by showing that it cooperates with mir-181d to target map1b and calm1 in the axons of primary sensory neurons during axon development. 26711345_3 we report that the fmr1-encoded protein, fmrp-mediated axonal delivery of mir-181d negatively regulates axon elongation by locally targeting the transcripts of map1b and calmodulin in primary sensory neurons. 22889583_1 our findings thus suggest that clic5 is directly regulated by mir-96 and mir-182 and that the target sequence in this regard is located between nucleotides 760- 766 within the clic5 3- utr. 22889583_2 our current data thus suggest that hei-oc1 cells are an appropriate in vitro system to verify that clic5 is regulated by mir-96 and mir-182 in inner ear hair cells. 22889583_3 taken together, these findings suggest that mir-96/-182 markedly downregulate clic5 expression by targeting the transcripts of these genes for degradation and not by inhibiting translation. 22889583_4 taken together,these data indicate that mir-96 and mir-182 directly bind and negatively regulate the protein translation of clic5 via a common binding site at nucleotides 760- 766 in the clic5 3- utr. 19684108_1 xist is regulated by tsix,xist's 40-kb antisense counterpart that antagonizes xist. 19684108_2 when tsix rna is down-regulated from xi-elect, one of the first changes to appear is a concentration of h3-k27me3 at the 5' end of xist, concurrently with enrichment for polycomb-repressive complex 2 . 19684108_3 only upon cell differentiation and the initiation of xci-when tsix rna was down-regulated from xi-elect-did prc2 bindxist chromatin and methylate h3-k27. 26047583_1 target scan analysis showed that dnmt1 has a binding site for hsa-mir-1264 within its 3'utr . 26047583_4 we show the targetscan analysis of the seed region of hsa-mir-1264 which potentially interacts with the 3'utr sequence of dnmt1 transcript. 20520763_2 however, ptb protein levels were decreased by 30- 40% in islets incubated in the presence of high glucose or sodium palmitate consistent with the observation that mir-133a inhibits ptb mrna translation by binding to the 3'-utr of ptb mrna , , and in line with the generally accepted notion that mirnas often decrease translation without affecting mrna stability and levels , . 21062812_1 in summary, c-myb is negatively regulated by both mir-155 and -424, while siah1 is down-modulated by mir-424 and c-ski is potentially downregulated by mir-155. 21062812_4 firefly luciferase reporters fused to the c-myb, siah1, c-ski and lats2-3'-utrs were cotransfected with mir-155 and -424 into hek 293-t cells in the indicated combinations. 21062812_7 mir-424 target siah1 but not lats2. 23197937_4 these data suggested that induced mir-145 expression during differentiation could inhibit adipogenesis by targeting irs1, and mir-145 may be novel agent for adipose tissue engineering. 26242299_1 these data suggest that decreased let-7f expression can be associated with increased il-23r expression and il-17a production in th17 cells from women compared with that in th17 cells from men. these data show that let-7f negatively regulates il23r expression and il-17a production in th17 cells and that the decreased let-7f expression in th17 cells from women results in increased il-17a production when compared with that in th17 cells from men. 21225860_2 molecularly, mir-340 directly target the c-met gene. 22819824_1 forcing the expression of mir-615-5p showed downregulation of igf-ii mrna, as well as inhibition of the luciferase activity in a luciferase reporter vector harboring the igf-ii-3'utr targetsequence. 22819824_2 mir-615-5p acts as tumor-suppressor in hcc through targeting igf-ii. 22819824_4 mir-615-5p expression was inversely correlated with igf-ii mrna expression in human hcc liver tissues. 22819824_5 furthermore, we have shown that igf-ii 3'-utr is a direct targetfor mir-615-5p that showed significant decrease in cell proliferation and migration upon its forced expression. 21131276_1 furthermore, mir-124 interacts with a conserved mir-124 binding site in the 3'-utr of neurod1 and negatively regulates expression of the proneuralmarker neurod1, a bhlh transcription factor for neuronal differentiation. 21131276_2 therefore, we performed both further loss- and gain-of-function studies to verify the functional effects of mir-124 on neurod1. 21131276_4 these results confirm that loss of mir-124 promotes neurod1 expression and that mir-124 is necessary for controlling neurod1 expression at the optic vesicle stage. 21131276_5 however, expression of lhx2 was also significantly downregulated , indicating that mir-124 is sufficient for repressing lhx2 transcription at both the optic vesicle and optic cup stages. 21131276_6 the above results demonstrate that mir-124 can directly targetthe mre in the 3'-utr of the neurod1 to repress gene expression. 26656471_1 we also confirmed that mir-27a is a negative regulator of the dkk2 gene using mir-27a overexpression and inhibition experiments and mutation analyses. 26656471_3 these results suggest that mir-27a inhibits the proliferation of cho cells by targeting dkk2. 18252210_1 the risk allele for rs12720208 disrupts a binding site for microrna-433, increasing translation of fgf20 in vitro and in vivo. in a cell-based system and in parkinson disease brains, this increase in translation of fgf20 is correlated with increased a-synuclein expression, which has previously been shown to cause pd through both overexpression and point mutations. 17637574_1 when over-expressing mir-26a, mir-26b and mir-141 the expression of a luciferase reporter containing the full-length 3'utr of serbp1 was strongly reduced indicating that serbp1 is under the control of the mirna pathway. 26787105_1 pten mrna has been known as one of mir-21 targets that significantly associated with several malignancies in human . 26787105_2 the correlation coefficient test indicated that pten mrna level was negatively correlated with mir-21 level . 22027184_1 these results point to lats2 as a mediator of the mir-372 and mir-373 effects on cell proliferation and tumorigenicity, although they do not exclude the participation of other direct mir-target. 22027184_2 lats2 downregulation and the possible participation of other mir-372&3-target in the overall observed mir effect on cellular transformation. 22027184_3 these results suggest that lats2 could be repressed at the post-transcriptional level by mir-372 and mir-373 in ags cells. 22027184_4 altogether, these results indicate that lats2 is indeed a direct target of mir-372 and mir-373 in ags cells. 22027184_5 altogether, these results indicate that lats2 is a functional target of mir-372 and mir-373 in ags cells and that the high expression of mir-372 and mir-373 confers to them a growth advantage through the inhibition of lats2 expression. 22027184_6 these data confirm that the caga-dependent accumulation of lats2 protein involves a post-transcriptional release of its expression mediated by the downregulation of mir-372 and mir-373. 22027184_7 altogether, these results reveal an unexpected mechanism involved in the cell cycle arrest upon infection: the caga-dependent derepression of lats2 by the downregulation of mir-372 and mir-373. 26125663_1 ccnb1 is target of mir-410. 26125663_2 ccnb1 mrna overexpression is associated with mir-410 downregulation in human gonadotroph adenomas. 23554909_1 furthermore, we demonstrated mir-1228* negatively regulated nf-kb activity in sgc-7901 gastric cancer cells and found that ck2a2 was a target of mir-1228*. 23554909_2 further investigations on the association between ck2a2 and mir-1228* demonstrated that the protein levels of ck2a2 was concomitantly down-regulated upon mir-1228* stable overexpression in sgc-7901 cells . 23554909_3 these results suggested that mir-1228* interacts with the ck2a2 mrna 3'-utr. 20585629_1 previously,we demonstrated that the hcmv encoded mirna, mir-ul112-1, targets a number of the virus's own genes, including the immediate early transactivator ie72 which is essential for driving acute replication of hcmv. 26622381_1 subsequently, the results of the luciferase assay, quantitative pcr and western blot analysis confirmed that hif-1alpha was an indeed a target gene of mir-18a. 22033216_1 in the current study, we measured the expression of mir-146a/b, and their target genes, irak1, irak4, traf6 in the peripheral mononuclear cells of patients with sj gren's syndrome and healthy controls by quantitative reverse transcription polymerase chain reaction. 22033216_2 we found that both mir-146a and mir-146b, furthermore, the gene of traf6 were significantly overexpressed in the sj gren's patients, whereas the expression of irak1 gene was significantly decreased. 20445018_1 the mpl 3' utr is a target of mir-28. 20445018_2 mir-28 recognizes the mpl 3' utr and inhibits its translation. 20445018_3 mir-28 inhibited luciferase expression by binding to mpl 3 'utr nucleotides 3524-3545. 20445018_4 importantly, expression of mir-28 did not reduce the level of endogenous mrna for mpl in mo7e or in hel cells . 20413099_1 recently, the activating nk cell ligand micb was found to be targeted by both ebv-mir-bart2-5p, kshv-mir-k12-7 and hcmv-mir-ul112-1. 19110058_1 we found that mir-20a, mir-17-5p, and mirna106b affected significantly luciferase expression . 19110058_5 using qrt-pcr, we found that mir-106b is expressed more abundantly in human brain than mir-20a and mir-17-5p. 20864249_3 3' utrs of wee1 and fbxl5 effectively decrease the relative renilla luciferase activity indicating direct interaction with mir-290-295 cluster members. 20864249_5 fbxl5 is coexpressed with mir-290-295 cluster, indicating the possibility that fbxl5 might be regulated by mir-290-295 cluster via translational inhibition in vivo. 25068583_1 mir-10a bound to gata6 directly and reduced gata6 expression. 25068583_2 this suggests that mir-10a directly and specifically binds to the 39utr of gata6. 25068583_3 our findings indicate that mir-10a interferes with the expression of gata6 by specifically binding its 3'utr. 25068583_4 our experimental study confirmed that mir-10a down-regulates the expression of gata6 by directly binding to its 3'utr and gata6 overexpression rescues the mir-10a-mediated depressive effect on the hcmpcs proliferation. 19965651_1 in particular, we provide experimental evidence that mir-146a modulates activation-induced cell death , acting as an antiapoptotic factor, and that fas-associated death domain is a target of mir-146a. 19965651_2 to directly confirm that fadd is a target of mir-146a, we determined the endogenous levels of fadd protein in prrl-146a and prrl-ct jurkat cells by intracellular staining. 19965651_3 these findings highlight a negative correlation between endogenous mir-146a levels and endogenous fadd protein in stimulated primary cd4+ t lymphocytes, thus supporting our previous results that indicate fadd as a target of mir-146a. 24375253_3 kit was identified to be a target gene of mir-218 by the luciferase reporter enzyme system, and the effect of mir-218 on the expression of kit protein in cells was determined using western blotting. 26350536_1 these results suggested that regulation of smad3 expression was closely linked to the level of mir-16-5p. 26350536_2 this result proved that modifications in the target site of smad3 3' utr canblock the function of mir-16-5p. 26350536_3 moreover, the mir-16-5p-mediated downregulation of aggrecan and type ii collagen was probably achieved via regulation of expression of the target gene smad3. 25472505_1 as shown in figure 4a, there are three mir-1269 binding sites in the foxo1 mrna 3'-utr, including one conserved and two poorly conserved binding sites. 25472505_3 the luciferase assay results showed that ectopic overexpression of mir-1269 decreased, but inhibition of mir-1269, increased luciferase activity of the pgl3-foxo1-3'-utr reporter . 25472505_5 collectively, these results suggest that mir-1269 directly targets foxo1 in hcc cells. 24751937_1 further examination revealed two specific mirnas, dre-let-7d and dre-mir-140-5p, were predicted in silico to bind to a primary regulator of metabolism, adenosine monophosphate-activated protein kinase , and more specifically the two isoforms of the catalytic subunit, ampkalpha1 and alpha2, respectively. 18328430_1 mir-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by e2f1 in parallel with its host gene, mcm7. in turn, mir-106b and mir-93 regulate e2f1 expression, establishing a mirna-directed negative feedback loop. 21529905_1 our results suggest that loss of expression of mir-200a may play a critical role in the repression of e-cadherin by zeb2, thereby enhancing migration and invasion in cd133/1+ cells. 21529905_2 these results suggested that zeb2 carry putative mir-200a binding sites and can be regulated by mir-200a. 21529905_4 4, when mir-200a was transfected, zeb2 mrna was lowered compared with the negative control group, with an 44% decrease, indicating that mir-200a could down-regulate the endogenous zeb2 mrna level. 21529905_5 furthermore, western blot assay result showed that mir-200a down-regulated zeb2 protein expression as well. in accordance with downregulation of zeb2, we observed a proportional increase in the level of e-cadherin mrna and protein, indicative of its influence on e-cadherin transcription. 21529905_6 these results demonstrated that mir-200a regulates endogenous zeb2 expression through both the mrna degradation and translational repression pathways. 26439035_1 there are direct interactions between mir-143 and the mirna recognition sites of uca1. 26439035_2 uca1 is present in ago2-containing rna-induced silencing complex , through association with mir-143. 26439035_3 through downregulating mir-143, uca1 can modulate breast cancer cell growth and apoptosis. 26439035_4 figure 2. uca1 can directly interact with mir-143 and regulate its expression in mda-mb-231 cells. 26439035_5 these results suggest that the uca1 can modulate breast cancer cell growth and apoptosis at least partially through mir-143. 24871972_1 two other micrornas, mir-448 and mir-196, directly target the core and ns5a coding region of the hcv genome, respectively. 26276160_1 mechanically, data from luciferase reporter assays revealed that mir-32 directly targeted to the 3 ' -untranslated region of phlpp2. 26276160_2 taken together, our results demonstrated that phlpp2 is a bonafide target of mir-32. 26276160_3 further experimental results demonstrated that phlpp2 was direct targets of mir-32 in breast cancer cells. 26118667_1 cdk5r1 is a potential target of microrna-195 20219467_1 here, we identified myeloid differentiation protein 88 as a target gene of mir-155, and found that mir-155 decreased myd88 expression at the protein but not the mrna message level, suggesting that the mir-155-mediated inhibition is a post-transcriptional event. 20219467_2 taken together, above results suggest that mir-155 target the predicted site in the myd88 gene. 20219467_3 above data suggest that mir-155 might down-regulate the targetprotein myd88 through inhibition of translation. 20852262_1 in spite of these, the above results established that mir-200b and mir-717 are highly tonicity-sensitive and tonicty-responsive, suggesting strongly that these two mirnas might serve as tonicity-responsive factors that contribute to the regulation of orebp. 20852262_2 together, these results indicate that mir-200b and mir-717 are capable of modulating orebp expression. 20852262_3 these results suggest that mir-200b and mir-717 might exert their silencing effects on orebp through mirna- 3'-utr interactions. 20852262_4 these results suggest that the interactions between the putative mres on orebp-3'-utr and mir-200b or mir-717 were specific. 20852262_5 together, these results indicate that mir-200b and mir-717 regulate orebp by targeting orebp-3'-utr to destabilize the mrna and/or suppress protein translation. 20852262_6 together, they strongly suggest that mir-200b and mir-717 play important roles in osmoregulation/osmoadaptation by regulating the expression of orebp. 26292968_1 the luciferase activity in mutant type was higher than the one in wild type, indicating that the position of 377- 383 on 3- utr of mmp1 mrna mediates the targeting of mir-526b. 26292968_2 the overexpression of mir-526b induced the reduced activity of mmp1 3- utr luciferase. 26292968_3 however, the reduced activity by mir-526b was not observed with mutant type of mmp1 3- utr reporter vector containing the mutated sequences in predicted mir-526b binding site. 21628394_1 mir-223 posttranscriptionally down-regulates epb41l3 expression by directly targeting its 3'-utr. 21628394_2 figure 4.mir-223 posttranscriptionally downregulates epb41l3 expression by directly targeting its 3'-utr. 21628394_3 to further confirm that epb41l3 is a functional target of mir-223, we used western blot to examine the epb41l3 protein level after overexpression or knockdown of mir-223. 21628394_4 compared with the control, inhibition of mir-223 level in xgc-9811l cells could increase epb41l3 protein level . 21628394_5 similarly, in nugc-3 cells , upregulation of mir-223 level could decrease epb41l3 protein level . 21628394_6 taken together, these data suggested that epb41l3 is a direct target of endogenous mir-223. in conclusion, these data hinted us that twist/mir-223/epb41l3 pathway is involved in the mir-223-regulated gastric cancer metastasis process and may be a potential therapeutic targetfor gastric cancer metastasis. 20584986_1 heterologous reporter analysis verified that mir-375 repressed hud expression through a specific, evolutionarily conserved site on the hud 3' untranslated region. 20584986_2 at the targetsite on the hud mrna, the single-nucleotide substitution in mouse and rat, located 8 bases away from the seed region , did not affect the repressive influence of mir-375 on hud expression in mouse neuro2a or rat pc12 cells . 20584986_3 similarly, injection of be -m17 cells with lenti-gfp-mir-375 reduced the abundance of hud . 20584986_4 together, these data indicate that mir-375 suppresses hud protein expression in different species. 20584986_5 these results support the view that mir-375 selectively represses gfp expression through the hud mir-375 site. 20584986_6 together, these findings indicate that mir-375 promotes the recruitment of hud mrna to ago2/risc and suggest that ago2 mediates the repression of hud by mir-375. 20584986_7 together, these results indicate that mir-375 represses hud expression both by lowering hud mrna stability and by repressing hud translation. 21837748_1 interestingly, we observed that the mir-200a directly targeted the 3'-untranslated region of the hdac4 messenger rna and repressed expression of hdac4. 21837748_2 to validate the interactions between mirna and target these two hdac4 complementary sites were individually cloned into the 3'-utr of the firefly luciferase gene and cotransfected with mir-200a mimics or mirna negative control into smmc-7721 cells. 21837748_3 neither induction of expression nor the inhibition of mir-200a could change hdac4 mrna levels . 21837748_4 however, enforced mir-200a expression led to a reduction of hdac4 protein levels in comparison with the negative control in the two human hcc cell lines . 21837748_5 on the contrary, the inhibition of mir-200a increased the hdac4 protein levels . 21837748_6 these results strongly indicated that the expression of the hdac4 gene was translationally suppressed directly by mir-200a. 21837748_7 we next tested whether other mir-200 family members could change hdac4 expression. 21837748_8 these results demonstrate that mir-200a induced aberrant histone acetylation in hcc by targeting hdac4. 25916550_2 this indicates that ep2 could be another potential target of mir-149. 25916550_3 mir-149 targets il-6 and ep2, downregulating their expression in fibroblasts. 26286747_1 figure 2. mir-542-3p directly inhibits akt1 expression in astrocytoma. 26286747_2 therefore, these data suggest that mir-542-3p inhibits akt1 expression via direct interaction with its 3'-utr in glioblastoma cells. 26286747_3 these discrepancies imply that some other upstream regulatory molecules of akt1 phosphorylation may be simultaneously repressed by mir-542-3p. 26286747_4 taken together, these results indicate that ilk and pik3r1 as well as akt1 are bona fide targets of mir-542-3p in glioblastoma cells. 26286747_5 taken together, these data strongly demonstrate that mir-542-3p suppresses glioblastoma cell invasion through targeting the akt pathway by directly inhibiting akt1, ilk, and pik3r1 simultaneously. 26315788_1 furthermore, ectopic expression of mir-99b-3p inhibited oscc cell proliferation by downregulating glycogen synthase kinase-3 -beta , an mir-99b-3p' target gene, at the mrna and protein levels, both in vitro and in vivo. 26315788_2 consequently, pre-mir-99b/gsk3 -beta _utr transfected cells showed significant reduction of luciferase activity , which suggested that mir-99b-3p could suppress gene expression through its binding sequences at the 3'utr of gsk3 -beta. 26315788_3 these results indicated that mir-99b-3p might directly target the 3'utr of gsk3 -beta mrna and inhibit gsk3 -beta translation. 25623761_1 mir-34a may regulate sensitivity of breast cancer cells to adriamycin via targeting notch1. 25623761_2 on the contrary, the expressions of notch1 mrna and protein in mcf-7 cells transfected with mir-34a inhibitor were down-regulated. 22100165_1 table s10a genes that contribute to the enrichments of par-clip targets of mir-k1 from bc-1 libraries in downregulated mrnas in bjab/mir-k1 cells.table 22100165_2 s10d genes that contribute to the enrichments of par-clip targets of mir-k1 from bc-3 libraries in downregulated mrnas in bjab/mir-k1 cells. 26375440_1 above data showed that capn6 and pou2f1 were direct target genes of mir-449a. 26375440_2 figure 2: restoration of mir-449a down-regulates pou2f1 and capn6 expression. 26375440_3 these data clearly indicated that mir-449a promoted liver cancer cell apoptosis by down-regulation capn6 or pou2f1. 26851540_1 results from luciferase reporter assay showed that the relative luciferase activity in sgc-7901 cells co-transfected with pmirfoxa1 reporter plasmid and mir-1290 inhibitor was signi铿乧antly lower than sgc-7901 cells co-transfected with pmir-foxa1 reporter plasmid and negative control. 26851540_3 when sgc-7901 cells were transfected with mir-1290 inhibitor foxa1 expression level was up-regulated. 25995211_1 moreover, we directly validate both crem and icer as the targets of mir-1 establishing a feedback mechanism between cardiac-specific mirs and camp signaling. 25995211_2 crem and icer are targets of mir-1. 25995211_3 we further confirmed that mir-1 directly targets and represses the expression of crem and icer. 25201065_3 downregulation of rab14 partially replicated the mir-451-mediated dsbs induced by ionizing radiation . 25201065_4 mir-451 could be a potential target for enhancing radiosensitivity of npc cells by targeting rab14. 26098560_1 mir-217 overexpression significantly reduced the gpc5 mrna levels in the hgc-27 cells and mir-217 inhibitor significantly enhanced the gpc5 mrna levels in the hgc-27 cells. 26098560_2 western blotting was performed to examine the effects of mir-217 on the expression of gpc5. 26098560_4 analysis using available algorithms indicated that gpc5 was a theoretical target gene of mir-217 . 20039258_1 mutations of putative mir-204 binding sites upregulated the runx2 3'-utr reporter activity, suggesting that mir-204/211 bindto runx2 3'-utr. 20039258_3 collectively, our results demonstrate that runx2 protein level is negatively regulated, whereas expression of mir-204/211 are induced during the differentiation of mesenchymal progenitor cells and hmscs into adipocytes, suggesting that mir-204/211 could be the suppressors of runx2 in these cells. 20039258_4 these results suggest that mir-204/211 are expressed in mesenchymal progenitor cells from different origins and suppress runx2 expression. 20039258_5 these results suggest that endogenous mir-204/211 can reduce runx2 protein levels in st2 cells and hmscs. 20039258_6 mir-204 and mir-211 bind3'-utr of runx2 mrna to downregulate runx2 expression. 19726678_1 adam10 , serum response factor , and insulin-like growth factor 1 receptor that promote tumorigenesis were validated as target of mir-122 and were repressed by the microrna. 19726678_3 these results suggest that mir-122 negatively regulates adam10 expression by interacting with its 3'-utr. 19726678_4 these results suggest that the suppression of mir-122 may be one of the mechanisms involved in the up-regulation of adam10 in primary hccs. 26197878_1 we found that the semaphorin 3b gene is a theoretical target of mir-221, and there are seven mir-221 conserved binding sites on the 3- utr region of sema3b mrna . 26197878_2 we firstly analyzed the correlation of the expression of mir-221 and sema3b level in 30 human glioma samples using rt-qpcr, and out result presented that there was a negative correlation between mir-221 and sema3b . 26197878_3 we used luciferase assay reporters containing the wild type 3'-utr sequence and the mutant type of sema3b mrna to test the effect of mir-221 on the transcriptional activity. 21266359_1 we provide first-time evidence that demonstrates that the ectopic mir-1258 negatively regulates heparanase expression and activity, and results in the inhibition of bmbc cell invasion and onset of brain metastasis. 21266359_2 moreover, cotransduction of mir-1258 with a luciferase construct containing the 5- -ccu-3- deletion mutant failed to decrease luciferase activity . in addition, we investigated whether the mir-1258-mediated inhibition of hpse affected heparanase pathways. 21266359_3 thus, we conclude that mir-1258 directly target heparanase and may affect bmbc cell invasion and metastases through hpse-regulated proteins and akt signaling. 20857419_1 because mirna-26a has been predicted to target smad-1 and smad-4, we next assessed the direct effects of mirna-26a on the expression of these pro-differentiation tgf--beta/bmp cascade molecules . 26699387_1 a luciferase reporter assay detected mir-7b binding to the 3- untranslated region of gabbr1 that was absent after targeted mutagenesis. 26699387_2 in cultured hek293 cells, we determined the binding of mir-7b to the 3'-utr of gabbr1 gene. 26699387_3 these observations suggest that after at 1 r stimulation and during chf, the gabbr1 protein is downregulated not by mrna degradation by mir-7b, but by post-transcriptional regulation. 23660952_1 downregulated mir-30a activated autophagy by inhibiting beclin-1 expression in h9c2 cell. 26580097_1 to further confirm whether sema3a was a direct target of mir-192-5p, 3'-utr of sema3a was cloned into a luciferase reporter vector; the putative binding site of mir-192-5p was mutated in sema3a 3'-utr. 26580097_2 the results showed that an overexpression of mir-192-5p significantly inhibited luciferase activity containing a wt 3'-utr of sema3a compared with negative control. 26577378_1 the results showed a moderate positive correlation with high confidence between the expression of mir-3661 and the ppp2ca gene , suggesting that the mir-3661 and ppp2ca genes have a correlating expression profile. . 26577378_3 these results clearly indicate that the pp2a function is suppressed by mir-3661 to directly target ppp2ca. 24447893_1 prdx-6 is suppressed by radiation-inducible mir-214 and is involved in the pathogenesis of radiation-induced skin injury. 23151846_1 finally, mir-137 induced apoptosis in melanoma cell lines and decreased bcl2 levels. 20655308_1 mir-1and mir-206 regulated hsp60 expression post-transcriptionally and acceleratedcardiomyocyte apoptosis through hsp60. in addition, mir-1/mir- 206-sponge could efficiently blocked mir-1 or mir-206 activity , and specifically reversed hsp60 protein reduction mediated by mir-1 or mir-206 . 20655308_2 post-transcriptional repression of hsp60 by mir-1 and mir-206. 25648114_2 target prediction algorithms identified a consensus mir-1224-5p recognition site in the 3'utr of the camp response element-binding protein gene, and this sequence was shown to directly confer mir-1224-5p repression in luciferase reporter assays. 25648114_4 conversely, over-expression of creb1 reversed the effect of mir-1224-5p on the proliferation, invasion, and apoptosis of glioma cells. 25648114_5 these data indicate that mir-1224-5p may inhibit tumor-associated activity in malignant gliomas by targeting creb1. 23542418_1 mir-191-mediated enhanced cell proliferation and migration are partly dependent on targeted downregulation of satb1. 23542418_2 these data collectively confirm that mir-191 directly target satb1 by binding to its 3'utr at position 717-724. 23542418_3 these results show that mir-191 and satb1 show inverse correlation of expression under various conditions tested, thus confirming satb1 as bonafide mir-191 target thus, overall, based on above results, we confirm satb1, cdk6 and bdnf as target transcripts of mir-191 in mcf7 cells with maximal effects been observed for satb1. 23542418_4 thus, mir-191-induced cell proliferation and migration seems to be partially dependent on satb1 downregulation. 23542418_5 these results show that mir-191 and satb1 show inverse correlation of expression under various conditions tested, thus confirming satb1 as bonafide mir-191 target 23361941_1 we further demonstrated that pni significantly inhibited microglial autophagy activation, whereas mir-195 inhibitor treatment increased autophagy activation and suppressed neuroinflammation in vivo and in vitro. 23361941_3 additionally, atg14 was identified as the functional target of mir-195. 20819939_1 we identify pax7 as one of the direct regulatory targets of mir-1 and mir-206. 20819939_2 inhibition of mir-1 and mir-206 substantially enhances satellite cell proliferation and increases pax7 protein level in vivo. 20819939_3 conversely, sustained pax7 expression as a result of the loss of mir-1 and mir-206 repression elements at its 3' untranslated region significantly inhibits myoblast differentiation. 18390668_1 in npc tumors, the lower mir-29c levels correlated with higher levels of multiple mrnas whose 3 utrs can bind mir-29c at target sequences conserved across many vertebrates. 18390668_3 moreover, for each of several genes tested, mutating the mir-29c target sites in the 3 utr abrogated mir-29c induced inhibition of luciferase expression. 18390668_4 most of the mir-29ctargeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin 1, that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of npc. the 3 utrs of all of these 10 candidate target genes elicited significantly decreased luciferase activities in mir-29c transfected cells. 25321480_1 mir-29b directly targets the 3'-utr of icat. the activity of the reporter gene containing the mut 3'-utr was not affected by mir-29b , indicating that mir-29b represses icat protein expression by specifically binding to the predicted target sites in the icat 3'-utr. 19959559_1 furthermore, we noted a significant upregulation of mir-468 that target lsh and leads to its decreased expression in thymus in the progeny of exposed parents. 19959559_3 therefore, we propose that mir-468-mediated suppression of lsh leads to aberrant methylation of line1 and sine b2 in the thymus tissue of the progeny of exposed parents. 15179038_1 experiments indicated that at the same time oct-4 expression increased while expression of h19 became barely detectable. 15179038_2 so this suggests that expression of h19 and oct-4 reflect the two opposite developmental paths of embryonic cells. 17260024_1 upregulation of mir-15a,mir-15b, mir-16-1, let-7a-3, let-7c, let-7d, mir-223,mir-342 and mir-107, whereas mir-181b was downregulated in in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid treatment. 25190211_3 moreover, ezh2 expression was downregulated in the f5m2 cells treated with the mir-101 mimics compared to cells treated with the nc mimics or the untreated cells. 25190211_4 mg63 cells treated with the mir-101 mimics also exhibited a lower expression level of ezh2 than cells treated with the nc mimics. 25190211_5 these results together reveal a negative correlation between mir-101 and ezh2 in osteosarcoma, and knockdown of ezh2 by sirna inhibits the migration and invasion of osteosarcoma cells. 26437444_1 on investigating the mechanisms involved in il-23 mediated migration and invasion, we observed that mir-25 promotes the migration and invasion of thyroid cancer cells by directly binding to the 3'-utr of socs4 that leads to the inhibition of socs4. 26437444_2 together, these results suggest that socs4 is a target of mir- 25 in k1 cells and wro cells. 26437444_3 these results suggest that the inhibition of socs4 expression is responsible for the ability of mir- 25 to promote cell invasion and migration. 26437444_4 taken together, these data suggest that mir- 25 is the key component involved in il-23-mediated thyroid cancer cell migration and invasion through the inhibition of socs4 expression. 22295098_1 these findings indicate that mir-152 indirectly up-regulated eralpha expression through its binding to dnmt1. 22295098_2 msp analysis also showed that dna methylation at eralpha was reduced by mir-152 precursor in the lps-treated cells . 22295098_3 however, dna methylation at eralpha was increased by mir-152 inhibitor. 22295098_4 therefore, we demonstrated a consistent change between dnmt1 and eralpha methylation by the change of mir-152 levels. 22199253_1 functional analyses demonstrated that this region of hbii-180c can influence the alternative splicing of fgfr3 pre-mrna, supporting a role for some snornas in the regulation of splicing. 22199253_2 as the expression of the gene hippi is generally low in most cell types, making experimental investigation difficult, we therefore concentrated on testing the possibility of a functional relationship between hbii-180c snorna and fgfr3 pre-mrna. 22199253_3 in summary, we conclude that the presence of hbii-180c snorna can affect the alternative splicing of fgfr3 pre-mrna by decreasing the accumulation of the 螖8-10 isoform. 22299047_1 the identification of mtor gene as a notable target of mir-99a and mir-99b opens the door to the possibility of therapeutic applications for mir-99a and mir-99b in cancer-like diseases such as lymphangiomyelomatosis. 22299047_2 taken together, these data suggest that mir-99a and mir-99b could induce mesenchymal phase nmumg to fully differentiate into smooth muscle cells by targeting the mtor gene. 22299047_3 we used a luciferase assay to validate most of the putative mir-99a and mir-99b target . 22299047_4 we further validated mtor gene as a target of mir-99a and mir-99b by using western blot approach . 22299047_5 however, in mesenchymal phase nmumg cells, mtor down-regulation affected cell proliferation and cell cycle concomitantly with the observed up-regulation of mir-99a and mir-99b . in addition, the identification of mtor gene as a notable target of mir-99a and mir-99b opens the door to the possibility of therapeutic applications for mir-99a and mir-99b in cancer-like diseases such as lymphangiomyelomatosis. 20633539_1 mir-21 protected human glioblastoma u87mg cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing bax/bcl-2 ratio and caspase-3 activity 21135128_1 thus, our subsequent efforts focused on mir-130a and mir-130b, two micrornas predicted to targetppargamma mrna . 21135128_2 among the mrnas showing increased expression during human adipogenesis , ppargamma mrna was predicted to be a target of mir-130a and mir-130b. 21135128_3 in a well-established model of murineadipogenesis , there was a similar decline in the conserved murinemir-130a and mir-130b and a concomitant increase in mrnas encoding adipocyte-specific proteins . 21135128_5 as shown, overexpression of mir-130a in 3t3-l1 cells significantly lowered the abundance of ppargamma mrna and differentiation markers adipsin and adiponectin mrnas; reducing mir-130a function significantly upregulated adipsin and ppargamma mrna levels. 21135128_7 after joint transfection of mir-130a and mir-130b, ppargamma mrna levels and ppargamma protein levels were also potently reduced. 21135128_8 taken together, these findings indicate that mir-130 interacts with the ppargamma cr and 3'-utr, thereby repressing ppargamma mrna and protein levels. 21822286_3 the 3'-utrs of cfl2and lrp1 each contain one functional mir-200 target sequence, while sec23a contains two evolutionarily conserved mir-200 target sites that function cooperatively to suppress sec23a expression . 21822286_4 taken together, these data suggest that expression of sec23a and the secretory pathway are inhibited by mir-200s. 25184138_1 the tumor-suppressive effect of mir-375 was determined by in vitro assays; through gain-of-function studies we demonstrated that mir-375 can inhibit lscc cell proliferation, motility, and invasion, and promote their apoptosis. 25184138_2 ectopic transfection of mir-375 led to a significant reduction in igf1r and its downstream signaling molecule akt at both the mrna and protein levels in lscc cells. 25184138_3 our results suggested that downregulation of mir-375 is one of the molecular mechanisms for the development and progression of lscc by directly targeting igf1r and affecting its downstream akt signaling pathways. 25184138_4 furthermore, mir-375 and igf1r may serve as a novel therapeutic target for lscc. 23869222_1 in the present study, the human nin one binding protein was identified as a direct target of mir-326 and a potential oncogene in human glioma. 23869222_2 similar to nob1 silencing by shrna, overexpression of mir-326 in human glioma cell lines caused cell cycle arrest at the g1 phase, delayed cell proliferation and enhanced apoptosis. 22893198_1 more recently, mir-143 has been found to promote cox-2 down regulation in a bladder carcinoma cellular model, resulting in reduced cell proliferation and mobility . 19821056_3 subsequently, the stable cell lines with overexpression of microrna-17 were screened, and luciferase assay combined with the mutation 3'utr of pkd2 were performed to verify pkd2 is the target of mir-17. 19821056_4 moreover, rt-pcr and western blotting were used to determine the post-transcriptionally regulation of pkd2 by mir-17. 19821056_6 our study firstly found that the 3'utr of pkd2 was more conservation than that of pkd1, and microrna-17 directly targets the 3'utr of pkd2 and post-transcriptionally repress the expression of pkd2. 19821056_7 moreover, our findings also demonstrated that overexpression of mir-17 may promote cell proliferation via post-transcriptionally repression of pkd2 in hek 293t. 23731466_1 tgfbr1 and tp53 were both predicted to be regulated by high-expressed mir-148a.in 21857657_1 we found that lhx2 is an in vivo targetmrna of mir-124a. 21857657_2 these results suggest that lhx2 mrna is a mir-124a targetin the retina and that downregulation of lhx2 mrna by mir-124a is necessary for retinal cell survival. 21857657_3 these results suggest that a proper lhx2 protein level, which is affected by mir-124a, is required for the appropriate development of axons in the dentate gyrus. 21857657_4 these results suggest that lhx2 is a primary targetgene of mir-124a and is responsible for the rncr3 / phenotypes, including both the reduction of retinal cone cell numbers and mossy fiber elongation of the dentate gyrus. 23396200_1 rna helicase ddx5 and the noncoding rna sra act as coactivators in the notch signaling pathway. 26137120_1 these results indicate that mir-203 binds to the 3'-utr of bmi1 mrna and thus regulates its expression . 26919791_1 a dual-luciferase reporter assay was performed to confirm the direct regulation of mir-133b-5p on the target gene fas. 26919791_2 morphine may protect cardiomyocytes against h/r injury through upregulation of mir-133b-5p by targeting fas. 26919791_3 collectively, these results indicate that fas may be a target of mir-133b-5p. 26919791_4 we further identified mir-133b-5p and the fas gene as the critical mirna and target gene, which might contribute to the cardioprotection of mpc. 22178073_1 a luciferaseactivity significantly decreased in the transfectants suggesting that actual binding occurred between mir-1 and 3'utr of srsf9 mrna. 22178073_2 we used a vector encoding full-length 3'-utr of srsf9 mrna and found that the luminescence intensity was significantly reduced in the mir-1 transfectants compared to the counterparts . 22178073_3 the xtt assay demonstrated that obvious increase of cell proliferation was not found in srsf9-transfected cells compared with the controls and that cell proliferation of mir-1-transfected cells was significantly reduced even in the cells with co-transfection of srsf9 expression vector . 22178073_4 n summary, we revealed that mir-1 may function as tumor suppressors through repression of oncogenic srsf9 in bc, and restoration of mir-1 and srsf9-knockdown increased caspase-3/7 activity, resulting in apoptosis. 22586040_2 il-10 plays an important role in the dysregulated cytotoxic t cell response to hiv-1, and in silico algorithms suggested that let-7 mirnas target il10 mrna. 26852749_1 moreover, we identified a disintegrin and metalloproteinases 10 as a direct target gene of mir-448 in gc cell. 26852749_2 adam10 was a direct target gene of mir-448 in gc cell. 26852749_3 moreover, we identified adam10 as a direct target gene of mir-448 in gc cell, and adam10 expression was upregulated in gc tissues and cells. 26852749_4 these results demonstrated that mir-448 played as a tumor suppressor mirna partly through targeting adam10 expression. 17478730_1 aberrant expression of mirna in injured arteries is confirmed by qrt-pcr or northern blot analysis.downregulation of overexpressed mir-21 decreases neointima formation in rat carotid artery after angioplasty.inhibition of mir-21 decreases proliferation of cultured vsmcs.inhibition of mir-21 increases apoptosis of cultured vsmcs. 26238271_1 the results indicated that mir-34a was negatively correlated with met . 20061417_1 the expression of mir-146a was almost undetectable in mouse embryonic fibroblasts isolated from the rela knockout mice and was restored after reexpression of rela, thus indicating that mir-146a transcription was controlled by nf-kappab. 26291313_1 using a luciferase reporting system and sequence analysis, the potential target of mir-411-5p was identified as sprouty homolog 4 , which inhibits protein kinase calpha-mediated activation of mitogen-activated protein kinases , especially p38mapk phosphorylation. in addition, we confirmed the 3'-utr of spry4 as the functional target of mir-411-5p and mir-411-5p-m in the downregulation of spry4 at the protein level in the sjcrh30 arms cell line . 26291313_2 we explored the biological function of mir-411-5p by examining six potential targets, based on the predictions of three different bioinformatic algorithms, and identified spry4 as the most likely target gene of mir-411-5p. 19144716_1 bv mirna 2 is antisense relative to a sequence k100 nt upstream of the initiating aug of the ul30 gene, which encodes the catalytic subunit of the dna polymerase. 19144716_2 therefore, mirna 2 may regulate the expression of ul30 in the same way that the ebv-encoded mirna mir-bart2 regulates the expression of the ebv dna polymerase. 26359764_1 furthermore, we identified fscn1 as the functional target of mir-326 by directly targeting the 3 ' -utr of fscn1. 26359764_2 thus, we supposed that fscn1 as a major functional target of mir-326 regulating cell proliferation and metastasis. 26359764_3 meanwhile, we proved that fscn1 was directly negatively regulated by mir-326 at a posttranscriptional level, and as a major functional target of mir-326 regulating cell proliferation and metastasis. 26359764_4 these data indicated that mir-326 can bind to the 3 ' -utr of fscn1. 26359764_5 these data suggested that mir-326 negatively regulates fscn1 expression by directly targeting its 3 ' -utr. 21725366_1 computationalprediction and microarray results indicated that mir-187 directly targeted disabled homolog-2 , and luciferase reporter assays confirmed that the target site of mir-187 was located at the 3'-utr of the dab2 gene. 21725366_2 similar results were seen in protein regulation; overexpression of mir-187 suppressed endogenous dab2 protein, whereas antimir-187 increased it . 21725366_3 the inhibitory effect of mir-187 on dab2 protein levels was confirmed in other ovarian cancer cell lines. 21725366_4 figure 2 mir-187 targeted dab2 in ovarian cancer. 21725366_5 zeb1 is a known targetgene of mir- 200a. in those experiments, knockdown of mir-200a was confirmed by increased levels zeb1 and by increased activities of the luc-zeb1-3'-utr reporter . 21511813_1 mir-192 is a tumor suppressor that can target the rb1 gene to inhibit cell proliferation and induce cell apoptosis in lung cancer cells. 26062558_1 mir-92a directly targets p21 mrna and down-regulates p21 protein expression 26273737_1 furthermore, lincrna-p21 acted as an endogenous sponge by directly binding to mir-130b and decreased mir-130b expression. in addition, mir-130b reversed the inhibitory effect of lincrna-p21 on the growth of vascular endothelial cells. 26273737_2 fig. 4. lincrna-p21 interacts with mir-130b. 26273737_3 these data demonstrated that the mir-130b bound to lincrna-p21 induced the reduction of lincrna-p21 and may function as a cerna. 19278969_1 lmo2 is a direct targetfor mir-223. 19278969_3 importantly, mutation of six bases in the candidate mir-223 binding site totally abrogated mir-223-dependent repression. 19278969_4 the observed smaller decrease in lmo2 mrna compared to lmo2 protein might be the result of mirna- mediated mrna-decay coupled to translational repression. 19278969_5 these experiments demonstrate that mir-223 directly interacts with the lmo2 3'-utr. 19278969_6 as shown in figure 5a the enforced expression of mir-223 resulted in degradation of lmo2 mrna and in a decrease of about 60% of lmo2 protein levels. 23069713_2 we also discovered that luciferase activity is exclusively decreased by targeting egfr in hmscs transfected with mir-133a mimic. 23069713_3 these results indicate that the egfr is a target of mir-133a, which binds to the 3'-utr region of human egfr mrna. 26272182_3 these observations implicate that ang is a potential mediator in tumor-induced downregulation of mir-542-3p in ecs. 26272182_5 indeed, higher ang expression correlated with lower mir-542-3p expression , indicating the downregulation of mir-542-3p by ang in breast cancer patients. 21725369_1 previous studies have shown that bmi1 is a target gene of both mir-200 and mir-15 . 21725369_2 to confirm whether mir-200b and mir-15b target to bmi1 in tscc cells, we conducted luciferase reporter assays by evaluating the relative luciferase activities in the cells transfected with a reporter plasmid carrying mir-200b or mir-15b target sequence versus those transfected with a control plasmid. 21725369_3 however, when the mirna targeting sequence was mutated in the reporter plasmids, transfection with mimics of mir-200b or mir-15b did not influence the relative luciferase activity , suggesting that mir-200b and mir-15b directly suppress bmi1 translation in tscc cells. 21725369_5 figure 5 mir-200b and mir-15b regulate emt in cal27-res cells by targeting to bmi1. 21725369_6 collectively, these data suggest that mir-200b and mir-15b regulate chemotherapy-induced emt of tscc cells by targeting bmi1. 21725369_7 these findings suggest that mir-200b and mir-15b inhibit the metastasis of tscc in vivo probably via silencing bmi1. 22956257_1 our data showed pten mrna and protein levels were significantly increased in ir adipocytes compared with normal adipocytes, over-expression of mir-21 significantly decreased pten protein level, whereas it had no significant effect on pten mrna expression in ir-adipocytes. 22956257_2 these data indicated that pten was a target gene of mir-21 in 3t3-l1 adipocytes . 22956257_3 taken together, these results suggested the inhibition of pten expression by mir-21 led to activation of the pi3k/akt pathway without perturbing pten upstream signaling molecules. 21982894_1 the mature mir-155 binds to the 3'utr of bach1 mrna and inhibits the translation of bach1 protein. 22383162_1 luciferase assays and site-directed mutagenesis demonstrated that mir-506 specifically may bindthe 3'untranslated region of ae2 messenger rna and prevent protein translation. 22383162_2 luciferase assays and site-directed mutagenesis demonstrated that mir-506 specifically may bindthe 3'-utr region of ae2 mrna and prevent protein translation. 21586237_1 mir-221/222 were downregulated by endoplasmic reticulum stress in human hepatocellular carcinoma cells, which subsequently protected human hepatocellular carcinoma cells against endoplasmic reticulum stress-induced apoptosis through p27kip1 regulation. 25818238_1 also, mir-124 targeted polypyrimidine tract-binding protein 1 , which is a splicer of pyruvate kinase muscle 1 and 2 and induced the switching of pkm isoforms expression from pkm2 to pkm1. 21273303_1 mir-21 was identified as an mir expression signature of rankl-induced osteoclastogenesis that down-regulates programmed cell death 4 protein levels. 21273303_2 pdcd4, a target of mir-21, mrna expression was detectable by rt-pcr analysis , but pdcd4 protein was not detected by immunoblotting analysis in control cells , compatible with mir-21 regulation of pdcd4 expression in bmms at the posttranscriptional level. 21273303_3 pdcd4 protein levels were extremely up-regulated by mir-21 silencing compared with control . 21273303_4 taken together, the action of mir-21 to suppress pdcd4 protein expression levels in bmms is a prerequisite for induction of osteoclastic transcription factors, specific markers, and osteoclastogenesis. in addition, elevated pdcd4 protein expression levels by decreased mir-21 expression were remarkably attenuated by mir-21 overexpression, indicating that expression of mir-21 for down-regulation of pdcd4 is physiologically pivotal in osteoclastogenesis. 21273303_5 thus, osteopetrosis in dicer cko mice may be caused by impaired mir-21 levels and up-regulated pdcd4 protein levels in bmms. 26847831_1 in addition, both targetscan 5.2 and pictar gave high confidence predictions that cul5 would be a target of mir-182. 26847831_2 this prediction was supported by an evolutionarily deep conservation of two mir-182 binding sites in the cul5 3'-utr. 26847831_3 thus, at least in these two cancers, cul5 is a target of mir-182 such that cul5 downregulation is achieved, in part, through modulation of mir-182 expression. 21307095_1 through specific interactions with cognate sequences in the barx1 3'untranslated region, mir-7a and mir-203 repress barx1 expression in stomachmesenchymal cells and its function in inducing gastric epithelium. 21307095_2 thus, different computational algorithms predict barx1 mrna as a targetfor mir-7a and mir-203, which are expressed in a tissue-specific and temporal pattern compatible with a role in barx1 regulation. 21307095_3 to test whether mir-7a and mir-203 affect endogenous barx1 levels in a native context, we forced pre-mir expression in ismcs or cultured fresh e12 mousestomach mesenchymal cells without luciferase reporter genes. 21307095_4 both mir-7a and mir-203 reduced barx1 protein levels in these experiments, confirming mirna targeting of barx1 . 21307095_5 these data directly implicate mir-7a and mir-203 in regulating barx1 expression levels through the 3'-utr. 23185467_2 further, several micrornas, specifically mir-101, mir-1668 and mir-1681 were discovered to influence serpinb3 expression via its 3'-utr which suggests that post-transcriptional regulation influences serpinb3 expression in chickens. 22508041_1 c-jun is a novel targetgene of mir-155 in hek293a cells. 22508041_2 expression of mir-155 was markedly reduced and that of c-jun mrna and protein was significantly up-regulated in uva-irradiated hdfs. 22508041_3 mir-155 directly controls c-jun expression in hdfs at the post-transcriptional level and might function as a protective mirna in hdfs.c-jun is a direct targetgene of mir-155. 22508041_4 luciferase reporter assays were performed to examine whether a mir-155 binding site in the 3'- untranslated region of the c-jun gene is responsible for mir-155-mediated c-jun regulation in hek293a cells. 26589799_1 herein, we identify mgat4a, ogt and galnt13 as targets of mir-424. 26589799_3 overall, our data demonstrates that mir-424 can regulate mgat4a, ogt and galnt13 through binding to their 3'-utrs. 26589799_4 taken together this data argues that mgat4a is a direct target of endogenous mir-424. 26020803_1 in consistence, we found a higher mir-155 level and a lower foxo3a level in aspc-1 cells compared with capan-2 cells, indicating an inverse link between mir-155 and foxo3a . in contrast, mir-155 did not affect the luciferase activity in both cell lines transfected with mutated 3'-utr region of foxo3a, indicating direct binding of mir-155 to foxo3a in pancreatic cancer cells. 26020803_2 the current study showed that ectopic expression of mir-155 targets foxo3a, leading to decrease of two major antioxidants including sod2 and catalase. 26701852_1 the results reported herein show that prdm16 was inhibited by mir-101 directly and also through epigenetic regulation. 26701852_2 prdm16 was confirmed as a new target of mir-101 and shown to be directly inhibited by mir-101. 26701852_3 mir-101 also decreased the expression of prdm16 by altering the methylation status of the prdm16 promoter. 26701852_4 in addition, ezh2, eed and dnmt3a were identified as direct targets of mir-101, and mir-101 suppressed prdm16 expression by targeting dnmt3a which decreases histone h3k27me3 and h3k4me2 at the prdm16 core promoter. 26701852_5 we concluded that the 3'-utr of prdm16 is directly targeted by mir-101 at the predicted binding site. 26701852_6 thus, prdm16 may be considered a new target of mir-101 in astrocytoma cell lines. 26701852_7 these data indicated that mir-101 suppressed prdm16 expression via dnmt3a-mediated modifications of histone h3k27me3 and h3k4me2 at the prdm16 core promoter, and these effects did not occur though ezh2 and eed. 22264793_1 mir-31 negatively regulates the noncanonical nf-kappab pathway by targeting nf-kappab inducing kinase . 22264793_2 mir-31 inhibition inversely rescued the nik level, revealing that the cellular mir-31 level negatively affected that of the nik protein through its 3' utr sequence. 22264793_3 these lines of evidence collectively demonstrated that mir-31 recognizes and regulates nik mrna through specific binding to its 3' utr. in contrast, mir-31 inhibition resulted in accumulation of nik mrna and protein in hela cells . 22264793_4 taking together all these results, mir-31, which is almost completely absent in primary atl cells, appears to play a critical role in negative regulation of the nf-kb pathway by manipulating the expression of nik. 22264793_5 collectively, these findings indicate that mir-31 mediates apoptosis through repression of nik in atl cell lines. 26282166_1 figure 4: mir-146b-3p and pax8 regulate each other. 22425745_1 hbx up-regulates cd59 by let-7i at the post-transcriptional level, contributing to escape of hcc cells from complement-dependent cytotoxicity. 26081620_1 robo1 was found to be a direct target of mir-219-5p, and when overexpressed in mir-219-5p-expressing glioma cells, was able to restore proliferative and invasive ability. 26081620_2 mechanistically, we identified robo1 as a direct target of mir-219-5p in the regulation of gbm growth and invasion. 26081620_3 when co-transfected with mir-219-5p, only the wide type of robo1 3'-utr-driven luciferase but not mutant one showed a significant reduction in the luciferase activity ,indicatingthat the robo1mrna isa bona fide mir-219-5p target. 26081620_4 interestingly, in individual tumor sample, the level of mir-219-5p was negatively correlated with the level of robo1 , again supporting the robo1 is a direct target of mir-219-5p in gliomas. 21224345_1 taken together, our findings define a functional involvement for mir-616 and tfpi-2 in the development and maintenance of androgen-independent prostate cancer. 21224345_2 microrna-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor tfpi-2. 21224345_4 these findings indicate that mir-616 negatively regulates the expression of the tumor-suppressor tfpi-2. 25305453_2 bioinformatics analysis reveals a putative target site for mir-30e in the 3'-untranslated region of the abl gene. in agreement,luciferase assay verified that mir-30e directly targets abl. 17923093_2 reduction of atrophin levels in mir-8-expressing cells to below the level generated by mir-8 regulation is detrimental, providing evidence for a "tuning target" relationship between them. 24381057_3 further studies showed that mir-452 directly targets the 3'-untranslated region of cyclin-dependent kinase inhibitor 1b , ectopic mir-452 expression suppressed cdkn1b expression on mrna and protein level. 24381057_4 silencing cdkn1b by small interfering rna resembled the phenotype resulting from ectopic mir-452 expression. 26071398_1 lin28b is a direct target and functional effector of mir-125a-5p in melanoma. 26071398_2 lin28b gene is a direct target of mir-125a-5p. 20869334_2 these results suggest that atm might be the target of mir-100. 20869334_3 these results suggest that mir-100 inhibited atm expression in m059j cells by targeting the specific b1 site of the 3'-utr of atm. 20869334_4 these results confirm that up-regulating mir-100 in m059k cells induced radiosensitization is the consequence of the low-expression of atm. in summary, our data, to the best of our knowledge, demonstrate for the first time that atm is the target of mir-100, and indicate that over-expression of mir-100 is mainly responsible for the low expression of atm in m059j cells. 20869334_5 these data also demonstrate that mir-100 targeting atm could sensitize the cells to ir-induced killing. 21622680_1 the effect of mir-195 on apoptosis is mediated through down-regulation of sirt1 and bcl-2 and ros production. 24452416_1 in the pre-mir-222 transfection group showed increased expression of mir-222 and decreased expression of puma, enhanced proliferation and invasion abilities, and decreased apoptosis. 25087183_1 subsequently, we showed that the upregulation of mir-21 was mediated by hbx-induced interleukin-6 pathway followed by activation of stat3 transcriptional factor. 26129688_1 here, our aim was to determine if mir-193b targets cyclin d1 in prostate cancer. 26129688_3 we found reduced mir-193b expression in stage pt3 tumors compared to pt2 tumors in a cohort of prostatectomy specimens. 26129688_4 in 22rv1 pc cells with low endogenous mir-193b expression, the overexpression of mir-193b reduced ccnd1 mrna levels and cyclin d1 protein levels. 26129688_6 moreover, according to a reporter assay, mir-193b targeted the 3'-utr of ccnd1 in pc cells and the ccnd1 activity was rescued by expressing ccnd1 lacking its 3'-utr. 23372675_1 the effects of mir-221 were then assessed by cell viability, cell cycle analysis, apoptosis assay, and cisplatin resistance assay. in both cells, upregulation of mir-221 induced cell survival and cisplatin resistance and reduced cell apoptosis. 23372675_4 moreover, luciferase reporter assay and western blot confirmed that pten was a direct target of mir-221. 19584283_1 we proved that, by modulating cyclin g1, mir-122 influences p53 protein stability and transcriptional activity and reduces invasion capability of hcc-derived cell lines. 19584283_2 in addition, in a therapeutic perspective, we assayed the effects of a restored mir-122 expression in triggering doxorubicin-induced apoptosis and we proved that mir-122, as well as cyclin g1 silencing, increases sensitivity to doxorubicin challenge. 19584283_3 in patients resected for hcc, lower mir-122 levels were associated with a shorter ttr, whereas higher cyclin g1 expression was related to a lower survival, suggesting that mir-122 might represent an effective molecular target for hcc. 21986534_1 this overexpression of mir-155 may suppress theexpression of c/ebp-beta and creb by directly targeting their 3' untranslated regions . 21986534_2 we also performed a luciferase reporter assay to test whether mir-155 directly binds the 3'utrs of c/ebp-beta and creb . 21986534_4 taken together, these in vitro results suggest that mir-155 may inhibit the expression levels of c/ebp-beta and creb directly. 21814748_1 in reporter assays,mir-34a binds its putative targetsite within the axl 3'utr to inhibit luciferase expression. 21814748_2 given the correlation between low levels of mir-34a expression in cell lines exhibiting high levels of axl, and the putative targetsite for mir-34a in the axl 3'-utr, we hypothesize that axl is a direct molecular target of mir-34a. 21814748_3 fig. 2 mir-34a target the 3'-utr of axl and affects expression of a luciferase reporter construct. 21814748_4 in comparison to negative control treated hs578t cells, a 60% reduction in axl protein levels was seen following transfection with the mir-34a mimic, but just a 30% decrease in c-met levels . 21814748_5 these data suggest that in both mda-mb-231 and hs578t breast cancer cell lines, the affinity of axl as a targetfor mir-34a appears to be greater than that of c-met. 21814748_6 this resulted in a recovery of phospho-akt levels and supports the targeting influence mir-34a has on axl. 26160158_1 mir-141 binds to h19 in a sequence specific manner, and suppesses h19 expression and functions including proliferation and invasion. 26160158_2 mutation of the putative mir-141 target sites decreased the response to mir-141, indicating that mir-141 binds to h19 in a sequence specific manner. 26160158_3 taken together, these data are consistent with our hypothesis and indicate that h19 may interact with mir-141 to link mir-141 and the post-transcriptional network in gastric pathogenesis. 23579289_1 as osx is a master regulator of osteoblast differentiation, we deduced that mir-214 might play a role in osteoblast differentiation to validate the prediction, a series of 3- utr fragments comprising that from the wt, d1, d2, and d3 osx. 23579289_2 these results suggested that mir-214 binds to the osx 3- utr directly and that both site 1 and site 2 are the binding sites of mir-214. 17569660_1 we further found that meg3 stimulates expression of the growth differentiation factor 15 by enhancing p53 binding to the gdf15 gene promoter. 17569660_3 these data indicate that specific rna folding is critical to meg3 activation of p53. 17569660_4 these data indicate that transfection of meg3 dna does not cause p53 activation. 17569660_5 instead, transcription of meg3 is required for p53 activation. 26692949_3 taken together, these data indicated that creb1 was a direct target of mir-205 in crc. 26692949_4 furthermore, we identified that creb1 was a direct target of mir-205, and decreased expression of creb1 have the similar effects of mir-205 restoration on proliferation, migration and invasion of crc cells. 26674874_1 mir-155-3p in cd4+ t cells targets dnaja2 and dnajb1. 26674874_2 these data confirm that mir-155-3p, but not mir-155-5p, targets both dnaja2 and dnajb1 mrna directly and reduces their expression. 26674874_3 a molecular search highlighted and validated two hsp40 genes, dnaja2 and dnajb1, as direct targets of mir-155-3p in cd4 + tcells. 24898807_1 mir-122 is downregulated in 5-fu-resistant colon cancer cells, and pkm2 is a direct target of mir-122. 24898807_2 taken together, our results demonstrated that pkm2 is a direct target of mir-122 in colon cancer cells. 20385090_1 sfrs1 is a physiological target of mir-7. 20385090_2 sf2/asf directly binds the primary mir-7 transcript to promote its maturation. 20385090_3 mature mir-7 in turn represses the translation of sfrs1 mrna by targeting its 3'utr . 19908170_1 curcumin reduces the expression of bcl-2 by upregulating mir-15a and mir-16 in mcf-7 cells. 26590872_1 in addition, mus309 expression was significantly down-regulated in the overexpressed dmemir-314-3p larvae after their exposure to cr in comparison to control. 26379395_1 sirt1 has been reported to be a potential target of mir-9 in studies of insulin secretion . 26379395_2 moreover, with the online prediction tools pictar and targetscan , we found that mir-9a-5p binds to two different sites in the 3'-utr of sirt. the results showed that the luciferase activity of the wt sirt1 3'-utr in cells that were treated with a mir-9a-5p mimic was significantly decreased. 26379395_4 we found that the mrna and protein levels of sirt1 were increased in hscs upon application of a mir-9a-5p inhibitor. 26379395_5 following transfection with a mir-9a-5p mimic, sirt1 expression was decreased . 26379395_6 taken together, it was demonstrated that mir-9a-5p is able to target sirt1 and negatively regulate its expression. 26055138_1 specifically, mir-214 was overexpressed in cells together with a luciferase vector harboring the 3'-utr of pten or pdlim2 mrnas. 26055138_2 furthermore, mir-214 overexpression suppressed pten and pdlim2 mrna and protein levels . in addition, overexpression of mir-214 induced nf-kappab phosphorylation and subsequently the expression of il6 , indicating that pten and pdlim2 are direct downstream effectors of mir-214 involved in the regulation of the nf-kappab inflammatory response. 12123448_1 rdla inhibits the translation of the ldra mrna. 18644370_1 our chip experiments also showed that over-expression of mir-17-92 did not obviously decrease the abundance of e2f1 on the ptpro promoter . 18644370_2 these data indicate that ptpro is a target of mir-17-92. 18644370_3 therefore, it is possible that the overexpressed e2f1 first up-regulated ptpro mrna and then down-regulated ptpro protein expression by up-regulating mir-17-92 transcription, leading to the above phenomenon in reporter assays. 18644370_4 e2f1 overexpression indeed upregulated mir-17-5p, a member of the mir-17-92 cluster . 18644370_5 to further validate the co-regulation of ptpro by e2f1 and mir-17-92 in cell cycle progression, we first monitored ptpro mrna expression in synchronized hela cells , and found that ptpro transcription was up-regulated during s phase . 18644370_6 these results demonstrated a positive correlation between e2f1 and ptpro and a negative correlation between the mir-17-92 cluster, especially mir-17-5p and ptpro. 18644370_7 these results indicated that the mir-17-5p binding site in the ptpro 3'-utr reporter contributed to the inhibition of the reporter during late s phase. 18644370_8 therefore, our data suggeste a model where ptpro is co-regulated by e2f1 and mir-17-92. 20719877_2 several of the ebv bart mirnas from a single genomic cluster work together to down-regulate production of the ebv latency membrane protein 1 . 23851566_1 interestingly, it was demonstrated that mir-15b, mir-16, mir-20a and mir-20b co-regulated other angiogenic factors . 23851566_2 down-regulation of mir-126 in lung cancer cell lines, mir-200b in the diabetic retina, mir-93b under hyperglycemic conditions or mir-205 in glioma cell lines increased vegf-a expression . 23851566_3 additionally, mir-361-5p levels are inversely correlated with vegf-a expression in human cutaneous squamous cell carcinoma , mir-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting vegf-a , and mir-145 inhibits tumour angiogenesis, cell growth, invasion and tumour growth through the post-transcriptional regulation of vegf-a . 26055324_1 to validate myf5 as a target for mir-106b, we performed pre-mir-106b transfection experiments in satellite cells, and as displayed in fig. 26055324_2 13d, mir-106b overexpression leads to myf5 downregulation. 26055324_3 luciferase reporter assays further validated myf5 as a direct target for mir-106b . 26055324_4 additionally, pre-mir-106b transfection in pitx2c-overexpressing cells rescued myf5 upregulation to basal levels , supporting the idea that mir-106b is key in mediating the pitx2c effect on myf5 gene expression. 26884980_1 bioinformatic analysis showed that 3-phosphoinositide dependent protein kinase-1 was directly suppressed by mir-129-5p. in hk-2 cells, compared with control, endogenous pdpk1 mrna and protein levels were down-regulated in the cells with mir-129-5p transfection. 26884980_2 the 3'-utr of the pdpk1 gene contains binding sites for mir-129-5p according to bioinformatic analysis. 26884980_3 data showed that mir-129-5p inhibited emt of hk-2 cells induced by pdpk1 overexpression . 26194496_1 the results showed that in both mrna and protein levels, up-regulation of mir-325 decreased hmgb1 expression; on the other hand, inhibition of mir-325 raised hmgb1 levels . 26194496_2 these results suggested that mir-325 modulates hmgb1 expression by directly targeting its 3'-utr. 20007690_1 overexpression of mir-15b, -16, -195, and -424 suppressed the activity of a luciferase reporter construct fused with the 3'-untranslated region of arl2. 20007690_2 therefore, it was hypothesized that mir-15b, -16, -195, and -424 could down-regulate arl2, which decreases cellular atp levels via ant1. 20007690_3 mir-15b down-regulated both mrna and protein of arl2 . 20007690_5 a mixture of mir-15b, -16, -195, and -424 also decreased arl2 mrna and protein levels as well as cellular atp levels to a similar extent as with mir-15b . 20007690_6 these results suggested that mir-15b, -16, -195, and -424 have similar effects in the recognition and down-regulation of arl2 mrna. 20007690_7 the present data indicate that mir-15b, -16, -195, and -424 can modulate cellular atp levels in the heart by targeting arl2. 26261542_2 we further focused on kiaa1199 because of its strong regulation after hsa-mir-188-5p transfection on the mrna level detected by qrt-pcr, its potential direct regulation via the 3'-utr binding site, and its possible role in ra and hyaluronic acid degradation . 26261542_3 we analyzed kiaa1199 expression in early passage rasf after transfection with mir-188-5p control or mir and found a strong regulation of the expression of kiaa1199 on protein levels in rasf from two different donors confirming that kiaa1199 is directly regulated by mir-188-5p in ra. 22912826_1 mir-338-3p expression inhibited cell proliferation in lo2/hbx-d382 cells , and also negatively regulated cyclind1 protein expression. of the two putative mir-338-3p binding sites in the cyclind1-3'utr region, the effect of mir-338-3p on the second binding site was required for the inhibition. 23292834_1 mtor was a direct downstream target of mir-99a/100 in the escc cell lines. 23292834_2 together, these results demonstrated that mir-99a and mir-100 suppressed the expression of mtor in a post-transcriptional. the tumor suppressor function of mir-99a/100 resulted from inducing tumor cell apoptosis by targeting mtor. 23292834_3 the luciferase assays demonstrated that mir-99a/100 directly bound to the 3'utr of mtor to post-transcriptionally repress this targetwithout affecting the mrna level. 26402295_1 among the candidate target genes of mir-330-5p searched using microarray analysis, we found that the expression of pdia3 was directly regulated by mir-330-5p in the mouse keratinocyte. 26402295_2 we also demonstrated that the expression of pdia3 was directly regulated by mir-330 in the mouse keratinocyte. 26402295_3 these results suggested that pdia3 was a direct target of mir-330-5p in mouse keratinocytes. 23226427_1 our results show that mir-16 silences cox-2 expression inhepatoma cells by two mechanisms: a by binding directly to the microrna responseelement in the cox-2 3'-utr promoting translational suppression of cox-2 mrna; b by decreasing the levels of the rna-binding protein human antigen r . 23226427_2 these results provide further evidence that cox-2 mrna is post-transcriptionally controlled by mir-16. 23226427_4 the results suggest that mir-16 could specifically bind to the 3'-utr region of cox-2 and represses cox-2 translation reinforcing the hypothesis that cox-2 mrna is a direct target for mir-16. 23226427_6 the results demonstrate that mir-16 interacts with cox-2 mrna and promotes cox-2 protein decrease mostly through a translational repression mechanism. 23226427_7 these results suggest that mir-16 may exert its pro-apoptotic function partially through decreasing cox-2 expression. 23226427_8 these results agree with the in vitro data and suggest that mir-16 inhibits the proliferation of hepatoma cells, among other mechanisms, through downregulation of cox-2. 21703189_1 mir-125b regulates expression of pigf. to verify that pigf is a direct target of mir-125b, we performed studies using luciferase reporter constructs containing the mir-125b recognition sequence from the 3'-utr of pigf inserted downstream of the luciferase gene. 21703189_2 taken together, these findings indicate that pigf is a biologically relevant target of mir-125b. 20554777_1 the results showed that mirna 323 , mir-491, and mir-654 inhibit replication of the h1n1 influenza a virus through binding to the pb1 gene. 23696794_1 prl-1 is a functional target for mir-339-5p in crc cells. 21956116_1 furthermore, er stress activates creb through tox3, and creb is a target gene of mir-34a and is involved in neurite growth and synaptic plasticity. 22545021_1 we found that mir-196a suppresses the expression of the white-fat gene hoxc8 post-transcriptionally during the brown adipogenesis of white fat progenitor cells. 22545021_3 the mir-196a expression was suppressed in the transfected cells and the hoxc8 expression was recovered in the transfected adipocytes , indicating that hoxc8 suppression was mediated by mir-196a. 18075594_2 table 3.list of shared targets for mir-k12-11 and mir-155 validated in this study.of 18075594_3 these, hivep2 and sla are also predicted targets for mir-155. 14729570_1 let-7 bind to six sites in the 3'utr of the mrna of its target gene, lin-41, to down-regulate lin-41,and this interaction is dependent on two conserved let-7 complementary sites . 21283765_1 pro-proliferative target genes cyclind1 and e2f1 as well as anti-proliferative target cdkn1a , pten, rb1, rbl1 , rbl2 were shown as common target for mir-17, -20a, and -106b. 21236259_1 we recently reported that microrna-221 regulates icam-1 translation through targeting the icam-1 3'-untranslated region . 21236259_2 we previously demonstrated that mir-221 target icam-1 3'-utr, resulting in translational repression in biliary epithelial cells . 21236259_3 taken together, the above data suggest that down-regulation of mir-221 is required for the up-regulation of icam-1 protein in host epithelial cells following c. 18424436_3 a second mechanism involves the prrf rnas, which may be able to bypass antr and repress anta directly.a 18424436_4 region of significant complementarity was identified between both prrf rnas and the translation initiation site of antr, which led to the hypothesis that an interaction between prrf and the antr mrna is responsible for the repression of anta by prrf. the repression of anta by prrf may occur by direct interaction with the anta mrna and indirectly via degradation of the antr mrna. 24965127_1 analyses with targetscan and microcosm targets bioinformatics tools led us to discover the mir-29b response elements in the 3' utrs of the apoptosis regulators caspase-7 and naif1. 24965127_2 to identify whether the 3' utrs of caspase-7 and naif1 are functional targets of mir-29b, we cloned the partial sequences and corresponding mutations of caspase-7 and naif1 3' utrs into the dual-luciferase reporter vector pmirglo. 24965127_3 next, we determined whether mir-29b overexpression affected caspase-7 and naif1 expression using real-time pcr and western blot. 24965127_4 the results showed that caspase-7 and naif1 expression were significantly inhibited by mir-29b mimics figs. 24965127_5 1d and.in conclusion, these findings suggest that mir-29b directly targets caspase-7 and naif1 and downregulates their expression. 24965127_6 taken together, these data indicate that mir-29b downregulates caspase-7 and naif1 expression and inhibits apoptosis. 26321631_1 using 3 ' utr constructs, we found that mir-93 mimics inhibit tbx3-3 ' utr-regulated luciferase activity, thereby confirming tbx3 as a target for mir-93 . 26321631_2 these results demonstrate that tbx3 is a functional downstream target of mir-93 and plays an important role in embryonic early adipocyte precursors and their differentiation into adipocytes. 26321631_3 also, we showed that tbx3 is a direct target of mir-93 in vitro. 22228303_1 we identified sirt1 as a direct target of mir-138, -181a, and -181b, whereas np63 expression was inhibited by mir-130b. 22228303_2 mir-130b's overexpression in proliferating hekn down-regulated deltanp63alpha levels, as shown in the western blot in fig. 22228303_5 2.mir-130a targets p63 mrna at its 3'-utr and decreases hekn proliferation. 20006626_1 pten as a target of mir-494 and expression in 16hbe-t cells. 20006626_2 these findings suggest that mir-494 post-transcriptionally regulates pten expression, suggesting that -渟eed region" mutation in binding sites can abrogate its regulatory role. 12581522_1 bc1 rna would bind to map1b, alpha-camkii, and arc mrnas regulated by fmrp. 12581522_2 significant stretches of complementarity between bc1 rna and those mrnas, and these regions are located on the longer stem loop of the bc1 rna. 20099276_1 furthermore, one of the predicted target of mir-489, downregulated in mcf-7/cddp cells, is mrp2 . 23185040_1 significantly reduced levels of akt1 protein were observed in the lysates of both hela and siha cells after mir-302-367 transfection , but there was little change in akt1 mrna levels , suggesting that mir-302-367 may reduce akt1 protein levels by inhibiting translation.this 23185040_3 similarly, expression of mir-302-367 suppressed the relative luciferase activity of the wild-type akt1 3'utr reporter by 26% in siha cells. 23185040_4 here, mutation of the mir-302s binding site abrogated the repressive effect , demonstrating the specificity of the akt1 target sequence. 23185040_5 this is the first report to identify akt1 as a direct target of mir-302-367. 24349493_1 furthermore, we performed luciferase reporter assay and showed that mir-140 mimic directly regulates klf9-3'-utr, thereby establishing and validating an example coregulatory network involving nr2f1, mir-140, and klf9. 24349493_2 this study discovered coregulatory interactions between nr2f1 and mirna-140 in their regulation of the gene krüppel-like factor 9 . 24349493_3 consistent with the luciferase-klf9-3'-utr activity that demonstrated a strong repression of klf9 by the mir-140 mimic , these data suggest that mir-140 may be a determining factor in regulating klf9 expression that is represented in the coregulatory network of nr2f1, mir-140 and klf9 . 24349493_4 together, these experiments provide molecular evidence that klf9 is directly coregulated by both mir-140 and nr2f1,further validating the bioinformatically predicted coregulatory network involving nr2f1, mir-140 and klf9. 25156120_3 however, the expression and biological role of mir-202 in osteosarcoma carcinogenesis and progression remain unclear. in this study, we demonstrated that mir-202 expression is significantly decreased in human os cell lines and specimens. 25156120_4 restoration of mir-202 expression could inhibit os cell proliferation, induce cell apoptosis, and suppress tumor growth in nude mice models. 25156120_5 we subsequently identified the transcription factor gli2 as a direct target of mir-202. 25156120_6 overexpression of gli2 blocked the inhibitory function of mir-202. 25156120_7 taken together, our results indicate that mir-202 acts as a novel tumor suppressor to regulate os cell proliferation and apoptosis through downregulating gli2 expression. 26084609_1 to verify whether b7-h1 is a direct target of mir-570,a dual-luciferase reporter system was employed. 26084609_3 these results suggested that this site in the 3'-utr of b7-h1 was exact regulation site for mir-570. 26084609_4 the increasing of mir-570 and decreasing of b7-h1 protein expression in hepg2 cells. 17616664_1 hepato-specific mir-122a was found downregulated in 70% of hccs and in all hcc-derived cell lines.mir-122a 17616664_2 can modulate cyclin g1 expression in hcc-derived cell lines and an inverse correlation between mir-122a and cyclin g1 expression exists in primary liver carcinomas 26855583_1 results from a dual-luciferase reporter system supported amot as a direct target gene of mir-497. 26855583_2 these results indicated that this site in the 3'-utr of amot was the specific regulation site for mir-497. 26855583_3 the findings of the present study support the hypothesis that the amot gene is a direct target of mir-497 in human osteosarcoma. 20124551_1 in the same experiments, we purified total rna from aliquots of suspended cells and monitored the abundance of the ciap2 mrna and gas5 ncrna by real-time pcr . 20124551_2 gas5 suppressed both binding of gr to ciap2 gres and ciap2 mrna expression in a dose-dependent fashion , indicating that gas5 inhibited association of gr with the ciap2 gres and repressed gr-induced transcriptional activity of the ciap2 gene. 26307093_1 luciferase experiments also corroborated vegf-a as a target gene of mir-29c-3p. 26307093_2 however, this inhibition was not observed when co-transfection was performed with the vector containing the specific mutated 3'-utr of vegfa , indicating that vegfa 3'-utr could be a direct target of mir-29c-3p. 26307093_3 furthermore, luciferase experiments indicated that vegf-a is a direct target of mir-29c-3p also in humans. 26286834_1 targetscan predicted that nfkbib is a potential direct target gene of mir-20a . 26286834_2 nfkbib expression was significantly lower in the mir-20a-high group than in the mir-20a-low group. 26286834_3 these results showed that mir-20a might negatively regulate nfkbib expression by directly targeting its 3 utr. 25312242_1 microrna-125b inhibits lens epithelial cell apoptosis by targeting p53 in age-related cataract. 26722467_1 furthermore, we showed that forkhead box protein m1 was a direct target gene of mir-204, and mir-204 regulated invasion and emt in ec by acting directly on the 3'utr of foxm1 mrna and suppressing its protein expression. 26722467_2 taken together, these results suggested that foxm1 is one of the direct targets of mir-204, and functional effect of mir-204 on ec cell lines is dependent on foxm1. 26791485_1 anti-oncogene pten was a direct target of mir-148a-3p. 26791485_2 we also identify pten as a target of mir-148a-3p. 25699650_1 we engineered h2ax overexpression in mir-138 overexpressed nci-h2081 cells. 25699650_2 protein quantification showed a signifi- cant h2ax downregulation after mir-138 overexpression and this effect is blocked by h2ax overexpression . 25699650_3 also, we found gammah2ax expression is downregulated with mir-138 overexpression and restored after h2ax overexpression. . 25699650_4 our results suggested that lower levels of mir-138 in sclc cells and associated high expression of h2ax are essential for dna damage repair. 26283043_1 on the basis of significant increases of mrna abundance after anti-mir treatment, our data indicate that the abundance of mrna encoded by the following hypertension gwas genes were suppressed by endogenous mirnas in endothelial cells predicted to target them: adrenomedullin by mir-26a-5p, mir-92a-3p, mir-92b-3p, mir-181a-5p and mir-181b-5p; plasma membrane calcium-transporting atpase 1 by mir-27a-5p, mir-27b-5p, mir-30a-5p, mir-181a-5p and mir-181b-5p, furin by mir-125a-5p; fibroblast growth factor 5 by numerous members of the let-7 family of mirnas, including let-7a, let-7e, let-7f, and let-7g; golgi snap receptor complex member 2 by mir-27a, jagged 1 by mir-21-5p; sh2b adapter protein 3 by mir-30a-5p, mir-98, mir-125a-5p, mir-125b-5p and mir-181a-5pm; and t-box 3 by mir-92a-3p and mir-92b-3p. 26283043_2 adrenergic receptor a1b mrna was suppressed by endogenous mir-22-3p in endothelial cells, adrenergic receptor a2a by mir-30a-5p, adrenergic receptor a2b by mir-30e-5p, adrenergic receptor b1 by let-7b, let-7c, let-7e and let-7g, and endothelin receptor b by mir-92a-3p and mir-92b-3p. 26283043_4 we found that nadph oxidase 4 mrna was suppressed by endogenous mir-92a-3p, mir-92b-3p, mir-99b-5p, and mir-100-5p, whereas catalase mrna and nadph oxidase 2 mrna were not significantly suppressed by the mirnas studied . 25563880_1 tgf-b2, a mir-200b target gene, expression is decreased in hypoplastic cdh lungs. 25563880_2 collectively, these data suggest that basal tgf-b-induced signaling is tempered by steady state levels of mir-200b, and that reducing mir-200b is permissive for tgf-b-induced signaling. 26323375_1 in the present study, fbxw7 was identified as a direct target of mir-92a. 26323375_3 collectively, these results strongly suggested that fbxw7 is a downstream target of mir-92a in hcc. 26373319_1 furthermore, we analyzed the binding energy and sites of uca1 and mir-16 using rnahybrid software, and the results implied that the mir-16 mature chain is partly complementary and thus potentially binds to uca1 . 26373319_2 this observation allows us to speculate that uca1 may directly bind to mir-16, and we constructed luciferase reporter plasmids containing either wild-type uca1 or a mutant uca1 . 26373319_3 then, umuc2 cells were transfected with the mir-16 or control mimics plus wildtype uca1 or a mutant uca1. 26373319_4 the results showed a dose-dependent repression of mir-16 by uca1 . 26373319_5 while mutating the mir-16 site in uca1 it no longer elicited such a significant effect . 26373319_6 taken together, these results indicated that uca1 contains the mir-16 binding site. 17437991_1 transfection of let-7 duplex to h1299 reduced the hmga2 mrna and protein . 17437991_2 down-regulation of hmga2 mrna by let-7 was also evident in tera-2 and retinoblastoma cell lines y79 and weri-rb-1 . 17437991_4 transfection of let-7 decreased the expression of only full-length hmga2 mrna, but not the truncated hmga2 mrna without the 3'-utr.et-7 22537031_1 bioinformatics integration of mirna expression and proteomic data highlighted two potential mirna/protein targetpairs: mir-141/ywhag and mir-520e/rab11a ; the functional interaction between these mirnas and their targetsequences on the corresponding mrnas was confirmed by luciferase assays. 22699519_1 the cancer cell apoptotic death was due to a marked viral-induced inhibition of microrna-let-7d that, in turn, upregulated caspase-3 activity. 26253191_1 as klf6 has been shown to induce tgf-beta during rsv infection and tgf-beta has been shown to suppress mir-24 expression, the effect of klf6 gene silencing on mir-24 expression was examined. 26253191_2 mir-24 expression was considerably upregulated, supporting the hypothesis that ns1-induced tgf-beta suppresses mir-24 expression and removing klf6, the positive inducer of tgf-beta, relieves tgf-beta-mediated mir-24 suppression. 18591254_1 we demonstrate that mir-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including reck and timp3, suppressors of malignancy and inhibitors of matrix metalloproteinases . 18591254_2 our data suggest that mir-21 contributes to the glioma malignancy by down-regulation of mmp inhibitors that leads to activation of mmps thus promoting invasiveness of cancer cells. 22532441_3 using human corneal epithelial keratinocytes , we demonstrate that fih-1 is a direct target of mir-31. 22532441_4 lowering mir-31 levels in hceks with anatgo-31, which increases fih-1 and depletes corneal epithelial glycogen stores, is the reciprocal situation to hydroxylase inhibition by dmog. 26517090_1 a targeting site for hsa-mir-222 was identified in the 3'-utr of abcg2 mrna ,5a, and dual luciferase reporter assays were performed to confirm that mir-222 directly targets this sequence. 26517090_2 mir-222 directly targets and reduces the expression of abcg2 in tscc 23398486_1 using an in vitro luciferase reporter assay we confirmed a direct interaction between mir-218 and cdh2, mir-218 and nanog, and mir-449b and notch1. 23398486_2 mutant reporters of cdh2 and nanog were not repressed by pre-mir-218, which confirms that the target site directly mediates the repression . 23398486_3 taken together, our results show that 3 of our 6 predicted mirna-mrna interactions are confirmed, that mir-218 directly targets cdh2 and nanog, and that mir-449b directly targets notch1. 22152314_1 the result from apo-one homogeneous caspase-3/7 kit was consistent with the above two apoptotic assays, which showed that with mir-221 inhibitors, the activity of caspase-3/7 was significantly enhanced . 23595747_1 because the pten/mtor signaling pathway mediates axonal regeneration and the mir-17-92 cluster targets pten , we explored the possibility that elevation of the mir-17-92 cluster in the distal axons locally modulates pten proteins. 23595747_2 verexpression of the mir17-92 cluster also altered protein levels of pten, pmtor and pgsk-3-beta in the cell body fraction . 22326957_1 this finding suggests that cyclin d1 expression and g1 phase transition of hepatocytes the conservation of rhob targeting by mir-21 is further supported by a recent study showing that mir-21 promotes the defining features of the metastatic phenotype, migration, elongation, and invasion, by inhibiting the human gene in a breast cancer cell line . 22326957_2 viewed together, our findings suggest that rhob is directly suppressed by the surge in mir-21 expression occurring in the early phase of liver regeneration. 22326957_3 we found that mir-21 knockdown impaired g1 phase exit and s phase entry, and that additional rhob knockdown restored normal cell cycle progression, which confirms rhob as the critical target of mir-21 in promotion of g1 phase progression. 22326957_4 viewed together, our results exclude suppression of pten by mir-21 as the reason for akt1 and mtorc1 activation in liver regeneration and confirm our hypothesis that mir-21 facilitates rapid translation of cyclin d1 by relieving akt1 and its mediator, mtorc1, from inhibition by rhob . 25130806_1 over-expressed mir-17 and mir-20a promote cell growth and cell cycle progression, and inhibit apoptosis through negatively-regulating p21 and e2f1 after-transcriptionally. 22935141_1 by using immunoblotting and mirna-targetluciferase activity assay as showed in figure 3e and supplementary figure s2b and c, we confirmed that dnmt1 is a direct target of mir-148a/152 in bc cells. 22935141_2 intriguingly, we found that dnmt1 expression, which is one of the target of mir-148a/152, is inversely correlated with the expression levels of mir-148a/152 in bc tissues. 22935141_3 more importantly, we demonstrate that igf-ir and irs1, often overexpressed in bc, are two novel target of mir-148a/152. 22935141_4 our results suggest a novel mir-148a/152-dnmt1 regulatory circuit and reveal that mir-148a and mir-152 act as tumor suppressors by targeting igf-ir and irs1, and that restoration of mir-148a/152 expression may provide a strategy for therapeutic application to treat bc patients. 22935141_5 meanwhile, the levels of dnmt1, a direct target of mir-148a and mir-152, were inhibited by mir-148a and mir-152 overexpression. 22935141_6 the dnmt1 and mir-148a/152 form a negative feedback loop that is disrupted in bc cells. 21628588_2 thus, cellular context contributes to mirna-mediated regulation of runx2. 22750848_1 as shown in figure 6a, mir-34a down-regulated smad4 and id1/3 expression, and such regulation was through direct binding to a conserved consensus region in the 3'utr of smad4 based on the 3'utr luciferase reporter assay . in summary, mechanistic exploration guided by integrative analyses of tf binding site enrichment in context of this clr inferred network established a novel mechanism of actions by mir-34a whereby it exerts its diverse transcriptomic influences through the modulation of the tgf transcriptomic network through the direct binding of smad4 3'utr. 26744345_1 cdk4 was predicted to be a potential target of mir-613 by miranda, since the 3-utr of the cdk4 mrna contains a complementary site for the seed region of mir-613 . 26744345_2 indicating that mir-613 may suppress cdk4 expression through the mir-613 binding sequence in its 3'-utr. 26744345_3 these results show that mir-613 may regulate the expression of endogenous cdk4 by directly targeting the 3'-utr of its mrna and, thus, that human cdk4 may be a new target of mir-613. 26156803_1 these results indicate that mir-133a directly binds to the 3'-utr of igf-1r and inhibits it expression. 23479198_1 in the current study, we screened and identified ltf is a bona fide target of mir-214 in npc cells. 23479198_2 by searching targetscan, we chose four candidate mirnas which were predicted to target ltf 3'-utr, and identified that mir-214 can indeed suppress ltf in npc cells. 23479198_3 these results provide evidence that mir-214 directly recognizes the 3'-utr of ltf mrna and inhibits ltf transcription and translation. 25592968_1 17-beta-estradiol regulates cell proliferation, colony formation, migration, invasion and promotes apoptosis by upregulating mir-9 and thus degrades malat-1 in osteosarcoma cell mg-63 in an estrogen receptor-independent manner. 23860036_1 the western blotting results showed that overexpression of mir-22 in cardiomyocytes significantly down-regulated pten expression level, while atrovastatin could inhibit endogenous mir-22 expression and markedly increased pten protein level . 21304604_1 taken together, our results indicate that mir-126 is a novel mirna that target sox2, and plac1 may be a novel downstream targetgene of sox2 in gastric cancer cells. 21304604_2 we also performed quantitative real-time rt-pcr analysis of sox2 mrna expression, and found that exogenous mir-126 modestly but significantly suppressed the sox2 mrna level in hsc43 cells . 21304604_3 interestingly, exogenous mir-126 transfection dose-dependently decreased the sox2 protein level in the mouse es cells , suggesting that mir-126 represses sox2 expression in various species and cell lineages. 21304604_4 moreover, the double deletion mutant vector, del-ab, showed complete reversal of the inhibitory effect of the pre-mir-126 co-transfection , indicating that mir-126 directly inhibits sox2 expression by targeting the two bindsg sites in the 3'-utr of sox2 mrna independently. 21304604_5 these data indicate that the mir-126 expression level is mostly opposite to the sox2 mrna and protein levels in gastric cancer cell lines. 21888875_1 these results strongly indicate that mtss1 gene expression is directly and translationally suppressed by mir-135a. 23208495_1 in conclusion, mir-7 is a novel mirna with tumor suppressive function in colon cancer by targeting oncogenic yy1. 23208495_2 yy1 promotes colon cancer growth through inhibiting p53 and promoting wnt signaling pathways and serves as an independent prognostic biomarker for crc patients. 26400166_1 figure 1. dbl-1, sma-6, daf-4, daf-1 and daf-7 mrna levels are upregulated in the mir-58 family mutant. 26400166_2 apparently, the 3'-utrs of daf-1 and daf-4 are the most efficiently mediators of genetic repression by the mir-58 family, as their means were the lowest for any tested mirna. 26400166_3 the 3'-utr of sma-6 could also inhibit luciferase expression with any of the mir-58 family members tested. in contrast, dbl-1 3'-utr activity seemed more restricted. 26400166_5 finally, the 3'-utr of daf-7 seemed unable to inhibit luciferase gene expression through any of the mirnas , with the possible exception of mir-58, because of a small but statistically significant difference with respect to control mir-67. 26400397_1 based on the results of a luciferase-reporter assay and quantitative rt-pcr and western blotting analyses, we found that smad5 is a target gene of both mir-23a and mir-27a. 26400397_2 fig. 3 mir-23a and mir-27a directly target smad5 in granulosa cells. 26400397_3 thus, these data strongly suggest that smad5 is a direct target of mir-23a and mir-27a. in conclusion, mir-23a and mir-27a positively regulate the fasl-fas pathway by targeting smad5 in granulosa cells. 22582938_1 previous studies have suggested that microrna-182 functions as an oncogene and plays a role in tumorigenesis, through regulation of foxo3a. 26261511_1 additionally, we demonstrated foxo1 is a direct target of mir-135a and transcriptionally down-regulated by mir-135a. 26261511_2 furthermore, we demonstrated that the tumor suppressor gene foxo1 is a direct target of mir-135a. 26261511_3 collectively, these results indicating that foxo1 is a target of mir-135a in malignant melanoma cells. 26261511_4 to explore the mechanism of mir-135a-induced cell proliferation, we investegated that mir-135a suppressed foxo1 expression via directly targeting its 3'-utr. 26183158_2 mir-595 was predicted by 5 databases, and mir-4487 was only predicted by targetscan. 26183158_3 these results indicate that mir-4487 and mir-595 may negatively or positively regulate ulk1-mediated autophagic pathway in sh-sy5y cells, respectively. 22367207_2 overexpression of mir-378 enhanced apoptosis of cardiomyocytes by direct targeting of igf1r and reduced signaling in akt cascade. 22367207_3 our study identifies mir-378 as a new cardioabundant microrna that targets igf1r. 22367207_4 we found that mir-378 promotes cardiomyocyte apoptosis by directly targeting igf1r and consequently inhibiting igf1-mediated activation of akt. 22367207_5 taken together, these results suggest igf1r 3' utr as a bona fide mir-378 target. 25426550_1 twist1 is downregulated by mir-520d-5p. 25426550_2 , we concluded that the 3'-utr of twist1 is directly targeted by mir-520d-5p at the predicted binding site. 25426550_4 the mir-520d-5p downregulation of twist1 leads to decreased mir-10b expression. 22367739_2 confirming that gp130 is a direct target of either or both mir-142-5p and -3p. 21350001_1 raf-1 and ccnd1 were identified as novel direct target of mir-195 and mir-497. 21350001_2 western blot analysis of raf-1 and ccnd1 in zr-75-30 and mcf7 cell lines showed that mir-195 or mir-497 transfection inhibited raf-1 and ccnd1 expression and erk1/2 phosphorylation . 21350001_3 similarly, we found that mir-195 and mir-497 inhibited cell growth and survival , and led to significant downregulation of both raf-1 and ccnd1 in vitro . 21350001_4 the results further demonstrate that raf-1 is a novel target of mir-195 and mir-497 in different experimental systems. 21112326_5 we obtained a statistically significant inverse correlation in a total of 40 tumors , indicating that mir-483-3p expression is inversely correlated with dpc4/smad4 in pancreatic cancer, and that upregulated mir-483-3p in pancreatic cancer suppresses the expression level of dpc4/ smad4, which in turn accelerates tumorigenesis. 22072795_1 repression of cugbp1 by mir-503 in turn altered the expression of cugbp1 target mrnas and thus increased the sensitivity of intestinal epithelial cells to apoptosis. 26500265_2 in this study, the interaction between gga-mir-181a and mybl1 was further verified by detecting protein expression levels of mybl1 after transfecting mir-181a mimic into md lymphoma cell line, msb1. 26500265_3 the result showed that protein level of mybl1 was lower in gga-mir-181a mimic transfecting group than that in the negative control group at 96 h post transfection, which indicated that mybl1 was a target gene of gga-mir-181a. 26149212_1 jak2 was identified as a mir-216a gene target. 26149212_2 taken together, these data indicated that jak2 is a mir-216a target in panc-1 pancreatic cancer cells. 26149212_3 jak2 was subsequently identified as a target gene that was downregulated by mir-216a. 26664144_1 additionally, we suggested that mir-148b suppressed cell proliferation, metastasis, and emt in lung cancer cells by directly binging to 3- -untranslated region of wnt1, blocking the wnt1/-beta-catenin signaling pathway. in this study, we identified that mir-148b, regulated by brg1, bound to two putative complementary regions in the 3'-utr of wnt1 mrna, inactivating the wnt/-beta-catenin signaling, resulting in inhibition of cell proliferation and metastasis in lung cancer cells. 26664144_2 moreover, we identified that brg1 positively regulated the expression of mir-148b and that mir-148b suppressed emt of lung cancer cells by regulating the wnt/-beta-catenin signaling via directly binding to wnt1 sequences. 22536353_1 foxa1 was revealed to be an important target of mirna-584 and mirna-1290. 22536353_2 these results further indicate that foxa1 is a target of mirna-584 and mirna-1290. 22536353_3 further luciferase reporter assays and western blot revealed foxa1 to be an important target of mirna-584 and mirna-1290. 22536353_4 these results indicated foxa1 as a strong candidate targetmolecule of both mirna-584 and mirna-1290. 22536353_5 among these five possible targettranscription factors, foxa1 had higher context scores in both the mirna-584 and mirna-1290 predictions. 22536353_6 subsequent firefly luciferase reporter assays and western blot analysis confirmed that foxa1 was knocked down by mirna-584 and mirna-1290. 26756969_1 additional analysis revealed that apelin-13 is a direct target of mir-503, as the overexpression of mir-503 decreased the protein and mrna expression levels of apelin-13. 26756969_3 the 3 ' utr of apelin-13 mrna was the target of mir-50. 21055388_1 cd44 mrna is a target of mir-199a-3p. 21055388_2 additional experiments were performed to establish that cd44 is a target of mir-199a-3p. 21055388_3 a putative mir-199a-3p binding site was located in the 3'-utr of cd44 . 21055388_4 the luciferase data and the reduction in cd44 protein indicate that cd44 is a target of mir-199a-3p. 21055388_5 examination of the cd44 mrna by qpcr showed that the cd44 mrna positively correlated with the cd44 protein, suggesting that binding of mir-199a-3p to the cd44 3- utr suppresses mrna levels . 20598588_1 foxp1 was a direct target of mir-34a in a 3 0 -untranslated region -dependent fashion. 20598588_2 the key mediator of the mir-34a effect appears to be the foxp1 transcription factor, which we found to be a direct target of mir-34a. 20598588_3 hence, repression of foxp1 by mir-34a is demonstrated in human and mouse cell lines, as well as in primary murine bone marrow, and is mediated through a conserved site in the 3 0 utr of foxp1. 20598588_4 our study extends these observations by demonstrating a specificity of mir-34a targeting for foxp1 in early b lymphoid development. 20041405_1 bcl-2 and mcl-1 are direct target of mir-29. 20041405_2 to verify whether bcl-2 and mcl-1 are direct target of mir-29, a dual-luciferase reporter system was first employed. 20041405_4 these results were also reproducible in hepg2 cells . in addition, antagonism of endogenous mir-29 resulted in the up-regulation of bcl-2 and mcl-1 proteins . 20041405_5 these data suggest that mir-29 may negatively regulate the expression of bcl-2 and mcl-1 by directly targeting the 3'-utr of their mrnas. 20478051_1 in our reporter assays, both mir-101 and mir-26a inhibit the expression of a reporter construct containing the 3'-utr of ezh2. in du145 cells, both mir-101 and mir-26a decreased the expression of ezh2 . 26884845_2 the group with bcl-2 overexpression showed that the expression of mir-27a and mir-17 was downregulated. 26884845_3 a pearson correlation analysis showed that hcc tissues with high expression of bcl-2 were related to a decrease in the expression of mir-27a, and the difference was statistically significant. 25140799_1 we then experimentally validated mir-203 as a direct regulator of src using cell transfection and luciferase assays and showed that mir-203 inhibited src expression and consequently triggered suppression of the src/ras/erk pathway. 25140799_2 finally, we demonstrated that the repression of src by mir-203 suppressed the proliferation and migration and promoted the apoptosis of lung cancer cells. 26703210_1 through bioinformatics analysis, fzd7 was predicted as a target gene of mir-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and western blot analysis. 21533613_1 restoration of the mir-375 expression in esophageal cancer cell lines downregulated the pdk1 expression. 21533613_2 furthermore, the mir-375 expression was found to be inversely correlated with pdk1 expression in esophageal cancer. 22431733_1 mir-132 induces mcp-1 partly via targeting pten, activates creb, and regulates genes related to cell-cycle and motility. 22431733_2 we identified phosphatase and tensin homolog as a novel target of mir-132 and demonstrated that mir-132 induces monocyte chemoattractant protein-1 at least in part via pten repression in rat vsmc. 22431733_3 we demonstrated that phosphatase and tensin homolog is a novel target of mir-132 and that mir-132/212 play key roles in ang ii-induced mcp-1 gene expression in rvsmc. 22431733_4 these results clearly demonstrate that pten is a direct and novel target of mir-132 in rvsmc. 25501305_1 in this study, we found that ang ii induced cardiomyocyte autophagy,together with down-regulation of mir-30a and upregulation of the beclin-1protein. 25501305_2 we also found that the beclin-1 protein is regulated by mir-30a, by ransferring a mir-30a mimic or amo-204 into the cardiomyocytes. 22080513_1 mir-29 targets include mcl-1, dnmt 3a/b, tcl1, p85 and cdc42 . 18854308_1 furthermore, s100b significantly down-regulated the expression of a key microrna, mir-16, which can destabilize cox-2 mrna by binding to its 3'-utr. 18854308_2 therefore, we hypothesized that diabetic stimuli such as s100b can increase cox-2 mrna stability not only via their effects on hnrnpk but also via concomitant decreases in the expression of mir-16 or in the interaction of mir-16 with the cox-2 3'-utr. 18854308_4 these results support our hypothesis that mir-16 down-regulation may be a key event during s100b-induced cox-2 mrna stability. 18854308_5 these results demonstrate that mir-16 binding to cox-2 3'-utr is increased in the absence of hnrnpk, further supporting a cross-talk between them. 26242262_1 bioinformatics analyses showed that mir-200 targeted the 3'-utr of zeb1 mrna to inhibit its translation, which was confirmed by luciferase reporter assay. 26242262_2 the luciferase activities were quantified in these cells, suggesting that mir-200 targets 3'-utr of zeb1 mrna to inhibit its translation . 26242262_3 these data suggests that mir-200 may bind zeb1 mrna to impair its translation. 21633093_1 also mir-296-5p levels inversely varied with puma mrna levels in human liver specimens. 21633093_2 our results implicate mir-296-5p in the regulation of puma expression during hepatic lipoapoptosis. 23588298_1 a genome wide gene expression analysis with mir-193a-transfected a2780 cells led to identification of arhgap19, ccnd1, erbb4, kras and mcl1 as potential mir-193a targets. 23588298_2 we demonstrated that mir-193a decreased the amount of mcl1 protein by binding 3'utr of its mrna. 26469956_1 ccnj was found to be downstream of mir-205, and it has been linked to the g2/m cell cycle in prostate cancers.we 26469956_2 have found that there are a couple of putative mir-205 binding sites in the 3- untranslated region of ccnj. 26469956_3 western blot analysis showed that overexpression of mir-205 in t24 cells attenuated the level of ccnj expression. 26469956_4 although the overexpression of mir-205 significantly inhibited the luciferase activity in the wt ccnj 3'-utr reporter, there were limited changes in cells with the mutated ccnj 3'-utr reporter, suggesting a direct interaction between mir-205 and the 3'-utr region of ccnj. 25278243_2 functional analyses indicated that mir-409-3p could inhibit growth, induce apoptosis, reduce migration and invasion in lad cells via inactivation of akt signaling by targeting c-met. 26629010_1 further experiment revealed that mir-592 repressed the expression of foxo3 by directly targeting the 3'-utr of the foxo3 transcript, which resulted in upregulating of the expression of cyclin d1 and downregulating of the expression of p21. 26629010_2 these results indicated that mir-592 directly targeted foxo3 in pc cells. 26629010_3 this is the first study to show that the foxo3 is negatively regulated by mir-592 through a specific target site within the 3'-utr. 21853360_2 furthermore, we examined whether mir-19a decreases the expression of pten. 21853360_4 pten protein expression levels were increased in mdr cells transfected with antimir-19a compared to control oligonucleotides-transfected mdr cells . 21853360_5 on the contrary, pten expression levels were downregulated in mcf-7 cells transfected with mir-19a mimics . in this report, our findings demonstrating the involvement of mir-19 in mdr via the modulation of pten provide new evidence in mdr development mechanisms of tumor cells. 21853360_6 additionally, mir-19 inhibitor restored the expression of pten and decreased the expression of mdr-1, mrp-1, and bcrp, and also sensitized mdr breast cancer cells to chemotherapeutic agents in vitro and in vivo. 21330408_1 transient and stable overexpression of mir-205 in a498 cells resulted in induction of g0/g1 cell-cycle arrest and apoptosis, as indicated by decreased levels of cyclin d1 and c-myc, suppressed cell proliferation, colony formation, migration, and invasion in renal cancer cells. 22120675_2 knock-down of plk1, which was a direct target of mir-100, yielded similar effects as that of ectopic mir-100 expression. 26459763_1 suggesting the specificity of the interaction of mir-140 and neat1. 22677042_1 we found that elevated levels of mir-222 in the mimics-transfected hct116/l-ohp and hct-8/vcr cells reduced the adam-17 protein level and the luciferase activity of an adam-17 3' untranslated region-based reporter and sensitized these cells' apoptosis to some anticancer drugs. 24340017_1 the initial association found for mir-29b/c is illustrated in figure 3awhich shows that mir-29b/c targets were elevated at 10 days , a time point when mir-29 was reduced . 26723899_1 meanwhile, another noncoding rna, microrna-203, was found to target the 3- untranslated region of the negr1 mrna. 26723899_2 this study has been aimed to characterize one such lncrna, bc048612 and a mirna, mir-203 that could regulate negr1 gene expression and elucidate their role in neurite outgrowth. 26723899_3 these results show that mir-203 directly regulates the negr1 mrna 3'-utr. 26723899_4 this study identified 2 non-coding rnas, the bc048612 lncrna and mir-203, which could modulate the expression of negr1 gene and mrna respectively. 25228082_1 we also found that mir-200b affected hypertrophic scarring through regulating the cell proliferation and apoptosis of human hypertrophic scar fibroblasts by affecting the collagen i and iii synthesis, fibronectin expression and tgf--beta1/alpha-sma signaling 21656127_1 we demonstrated that mir-222 inhibited protein expression of ppp2r2a in nsclc cells by directly interacting with its 3'-utr region, leading to an obvious increase of p-akt. 21656127_2 these results suggested that overexpression of mir-222 is causally linked to downregulation of ppp2r2a and activation of akt signaling in nsclc cells. in this feed forward loop, hmga1 enhances the expression of mir-222 which depresses ppp2r2a protein expression in a post-transcriptional manner. 21656127_3 fig. 3 overexpressed mir-222 enhances akt signaling through targeting ppp2a2r mir-222 potentially inhibits ppp2r2a expression by directly targeting its 3' utr. 19219026_1 to verify that mir-23a and mir-23b are suppressed by myc and could be diminished by antisense mir-23 locked nucleic acid oligomers, northern analysis was performed and mir-23 was suppressed by myc and profoundly diminished by antisense mir-23 lnas . 19219026_2 using quantitative real-time pcr, we document that mir-23 levels increased with diminished myc expression and then decreased upon myc re-induction in a manner that is compatible with the gls protein levels seen in figure 1c. 19219026_3 we determined next whether mir-23 target and inhibits the expression of gls through the 3'-utr. 19219026_4 in this regard, we cloned the 3'-utr sequence of gls including the predicted binding site for mir-23 to the pgl3 luciferase reporter vector and transfected mcf-7 cells, which is known to express mir-23. 22950459_1 overproduction of tnf-alpha after ogd-induced microglial activation provoked neuronal apoptosis, whereas the ectopic expression of mir-181c partially protected neurons from cell death caused by ogd-activated microglia. 25145289_1 at the molecular level, we find that mir-378 targets phosphodiesterase pde1b in bat but not in wat. 25145289_2 these results demonstrated that pde1b is a direct target of mir-378 in bat. 25145289_3 our results suggest that suppression of pde1b by mir-378 and hence elevation of camp level might be part of the mechanism underlying bat expansion. 25145289_4 we reveal that mir-378 directly targets pde1b in bat, but not in wat, to increase intracellular camp content, providing a plausible molecular mechanism for bat expansion. 17401374_1 mir-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing kcnj2 and gja1 and this likely accounts at least in part for its arrhythmogenic potential. 23548312_1 mir-145 has been recently reported to repress embryonic stem cell pluripotency and the expression of various stemness-related genes including oct4, sox2 and klf4 , therefore, we examined the ability of the delivered mir-145 to target sox2 in the gscs. 23548312_2 we found that transfection of the cells with mir-145 mimic decreased the expression of sox2 mrna and protein in both hf2414 and hf2485 gscs. in addition, we employed a luciferase reporter plasmid containing the 3'-utr of sox2 and found that the mir-145 mimic significantly decreased the luciferase activity of this construct in the hf2414 gscs . 26400224_1 mir-152 interrupts expression of dkk-1 by binding to 3'-utr of dkk-1 mrna. 26400224_2 these results indicate that dkk-1 gene is directly regulated by mir-152. 26400224_3 on the other hand, upon knockdown of endogenous mir-152 by inhibitor, expression of dkk-1 mrna and proteins were significantly upregulated . 20216554_1 these hippo pathway components are targeted by two mirnas: mir-372 and mir-373 in mammals and mir-278 in d. melanogaster . 20216554_3 this is prevented by high levels of mir-372 and mir-373, which target lats . 19734943_1 in this study, high-throughput microrna expression analysis revealed that the expression of mir-140 was associated with chemosensitivity in osteosarcoma tumor xenografts. 19734943_3 overexpression of mir-140 inhibited cell proliferation in both osteosarcoma u-2 os and colon cancer hct 116 cell lines, but less so in osteosarcoma mg63 and colon cancer hct 116 cell lines. 19734943_4 mir-140 induced p53 and p21 expression accompanied with g and g phase arrest only in cell lines containing wild type of p53. 19734943_5 histone deacetylase 4 was confirmed to be one of the important targets of mir-140. 19734943_6 the expression of endogenous mir-140 was significantly elevated in cd133 cd44 colon cancer stem-like cells that exhibit slow proliferating rate and chemoresistance. 19734943_8 taken together, our findings indicate that mir-140 is involved in the chemoresistance by reduced cell proliferation through g and g phase arrest mediated in part through the suppression of hdac4. 22898980_3 the use of an hsp90 inhibitor or knockdown of hsp90 decreased gw182 and mir-122 expression and significantly reduced hcv replication. 18728182_1 our findings indicate that mir-19a and b are up-regulated >100-fold in patient samples, >2,000 times in the cell lines , and are both almost absent in normal pcs and mgus. 18728182_3 mir-19a and mir-19b target socs-1, a negative regulator of il-6r/stat-3 pathway. 18728182_4 moreover, mir-19a and mir-19b mimics inhibited the expression of a reporter vector containing socs-1 3 utr, while mutation of the predicted mirna-binding site abrogated this effect. 18728182_5 these studies suggest a role of mir-19s in the il-6 antiapoptotic signal in the pathogenesis and malignant growth of mm. 18728182_6 u266 cells were transfected with mir-19s asos and bim expression was evaluated using immunoblot. 18728182_7 we found a significant increase of bim protein levels at 48 h after treatment with anti-mir-19s compared to scrambled oligonucleotides.bim 18728182_8 as a direct target of mir-17-92 and suggest a possible mechanism through which over-expression of mir-17 92 contributes to the antiapoptotic signals in mm. 18695042_1 both anti-mirs reversed the antiproliferative function of mir-17/20 , which is consistent with the functional role of cyclin d1. the abundance of aib1, a target of mir-17-5p repression, was inhibited as previously described by mir-17/20 . 18695042_2 the down-regulation of cyclin d1 and aib1 by mir-17/20 could be rescued by either anti-mir-17-5p or anti-mir-20a . 26838552_1 our results associate notch signalling to mir-223 downregulation in ra macrophages, and identify mir-223 as a negative regulator of the ahr/arnt pathway through arnt targeting. 26838552_2 the large number of mir-223 binding sites on the arnt 3'-utr precluded mutagenesis approaches to confirm silencing specificity. 26838552_3 arnt protein levels were reduced in pre-mir-223-expressing hek-293t cells , which supports mir-223 targeting of arnt mrna. 26838552_4 since pre-mir-223 overexpression did not affect ahr protein levels in these cells , our results suggest that high mir-223 levels functionally impair the ahr/arnt pathway in myeloid cells by reducing arnt protein levels. 21819631_2 reporter assay revealed that inhibition of mir-106b triggered a marked increase of luciferase activity of pgl3-wt-rb-3'utr plasmid both in hep-2 and tu212 cells, without change in luciferase activity of pgl3-mut-rb-3'utr . 26458815_1 mir-451a down-regulates tsc1 mrna expression in ags cells. 22179829_1 in reporter assays, the co-transfection of mir-133b with luciferase reporter gene linked to the wild-type 3'-utr of mst2 caused a significant decrease in luciferase activity , whereas the substitution of two nucleotides within the seed region effectively interrupted the reduction of luciferase activity by mir-133b . 22179829_2 mir-133b was also overexpressed in caski cells with adenoviral vectors to determine whether mir-133b affects the levels of mst2 protein and mrna. 22179829_5 these data indicated that mir-133b may directly target mst2 through both translational repression and degradation of mst2 mrna . 22179829_6 a previous report revealed that mir-133 inhibits cardiac hypertrophy through the targeting of two small guanosine triphosphatases, rhoa and cdc42 . 22179829_8 together, these results suggest the operation of a small signaling network in cervical carcinoma cells involving mir-133b, in which mir-133b targets mst2, cdc42 and rhoa to activate akt1 and erk . 22325199_1 dd remodeling is delayed in hbl-1 mutants whereas precocious remodeling is observed in mutants lacking the microrna mir-84, which inhibits hbl-1 expression. 22325199_2 by contrast, the mir-84 mutation did not significantly change expression of the hgfpc reporter, which lacks the hbl-1 3'-utr . 22325199_3 these results suggest that mir-84 regulates hbl-1 expression in dd neurons when remodeling is occurring. 23231923_1 we found that socs1 expression was elevated in the pc3 and lncap cell lines when mir-30d was inhibited by anti-mir-30d transfection . 23231923_2 taken together, these data strongly suggest that mir-30d directly binds to the 3'-utr of socs1, resulting in the downregulation of socs1 expression in pca. 23226446_2 the luciferase reporter gene assay showed interactions of gga-mir-181a with mybl1, gga-mir-181a with igf2bp3, and gga-mir-26a with eif3a. 23754305_1 genome-wide gene expression analysis and targetscan database studies showed that zeb1, which has been shown to promote tumor invasion and migration through e-cadherin gene silencing, is a promising candidate target gene of mir-200c. 23754305_2 overexpression of mir-200c in sn12-pm6 and 786-0 cells was concurrent with downregulation of zeb1 and upregulation of e-cadherin mrna and protein. 23754305_3 our results also showed that mir-200c levels were markedly elevated in sn12 mir-200c and 786-0 mir-200c cells, whereas the mrna and protein level of zeb1 decreased. 23754305_4 conversely, inhibition of mir-200c expression resulted in upregulation of zeb1. 23754305_5 these observations indicate that zeb1 is negatively regulated by mir-200c at the posttranscriptional level. 18942116_1 we showed that the development of hepatocellular carcinoma is characterized by prominent early changes in expression of mirna genes, specifically by inhibition of expression of micrornas mir-34a, mir-127, mir-200b, and mir-16a involved in the regulation of apoptosis, cell proliferation, cell-to-cell connection, and epithelial-mesenchymal transition. 26597380_1 interferon regulatory factor 7 is a direct target of mir-762 and overexpression of mir-762 reduced expression of irf7. 26597380_2 figure 3. irf7 was a direct target of mir-762 in the breast cancer cells. 26597380_3 furthermore, between pairs of breast cancer tissues, there was statistically significant inverse correlation between irf7 and mir-762 expression . 18381601_1 inhibition of snap25 expression by hiv-1 tat involves the activity of mir-128a. 18381601_2 we further show that mir-128a inhibits expression of the pre-synaptic protein snap25, whereas the anti-mir-128a partially restores tat/mir-128a-induced downregulation of snap25 expression. 25596743_1 we found that orp8 is down-regulated, whereas mir-143, which controls orp8 expression, is up-regulated in clinical hcc tissues as compared with liver tissue from healthy subjects. 25596743_2 orp8 overexpression triggered apoptosis in primary hcc cells and cell lines, which coincided with a relocation of cytoplasmic fas to the cell plasma membrane and fasl up-regulation. 26908019_1 c-myc is the targeted gene of mir-494. 26908019_2 c-myc was targeted by mir-494. 17695719_1 it was identified mir-372 permitting proliferation and tumorigenesis of primary human cells that harbor both oncogenic ras and active wild-type p53. 17695719_3 it was provided evidence that mir-372 is potential novel oncogene participating in the development of human testicular germ cell tumors by numbing the p53 pathway, thus allowing tumorigenic growth in the presence of wild-type p53. 19153141_2 here we report that the mirnas in two clusters suppress the cip/kip family members of cdk inhibitors , p21 and p27 . 19153141_3 we show that mir-25 targets p57 through the 3'-utr. 19153141_4 furthermore, mir-106b and mir-93 control p21 while mir-222 and mir-221 regulate both p27 and p57. 22382496_1 mir-335 directly target the 3'藟 utrs of rock1, mapk1 and lrg1. 22382496_2 here, we demonstrate that mir-335 directly target and downregulates genes in the tgf--beta non-canonical pathways, including the rho-associated coiled-coil containing protein and mapk1, resulting in reduced phosphorylation of downstream pathway members. 22382496_3 we have identified the rock1, mapk1 and lrg1 gene transcripts as direct target of mir-335 and have demonstrated that sirna-mediated inhibition of each of these genes significantly reduces the migratory and invasive potential of neuroblastoma cells in vitro. 23221562_1 loss of mir-122 expression in patients with hepatitis b enhances hepatitis b virus replication through cyclin g1-modulated p53 activity. 26503504_1 fascin homologue 1 was verified as a direct target of mir-24, and silencing fscn1 expression with small interfering rna inhibited npc cell proliferation and invasion . 26503504_3 furthermore, fscn1 was verified as a direct target of mir-24, and involved in npc cell proliferation and invasion. 23087254_3 the novel mir-7515 decreases the proliferation and migration of human lung cancer cells by targeting c-met. 23087254_4 these results suggest that mir-7515 plays an important role in the proliferation and migration of lung cancer cells through c-met regulation. 23087254_5 this result suggests that c-met was an authentic target of mir-7515. 23087254_6 the anti-7515 inhibitor did not affect the c-met levels through mir-7515 inhibition. 23087254_7 taken together, these results suggest that mir-7515 directly regulated c-met in a549 cells. 23087254_8 taken together, these results suggest that mir-7515 led to decreased cell-cycle-搑elated protein in a549 cells through c-met targeting. 23087254_9 these data suggest that mir-7515 negatively regulates the motility and migration of a549 cells and that this effect may be at least partly attributed to the targeting of c-met. 26586569_1 further studies revealed that overexpression of mir-205 resulting in commd1 downregulation at both the mrna and protein levels in sas, h460, and d121 cells . 26586569_2 taken together, these results suggest that commd1 expression is downregulated by mir-205, which is upregulated by nf-kappab activation during enrichment for stemness. 26586569_3 in summary, this study has shown that during the enrichment of stemness in hnscc cells and nsclc cells, commd1 is downregulated by mir-205, while mir-205 is upregulated upon nf-kappab activation. 26656045_1 mmp9 was identified as a target of mir-133a. 26656045_2 knockdown of mmp9 induced effects on np cells similar to those induced by mir-133a. 26656045_3 taken together, the results demonstrated that mir-133a directly recognizes the 3'-utr of mmp9 transcripts and regulates its expression at the post-transcriptional level. 22260523_1 mirna transfection and luciferase assay confirmed that bcl-2 was regulated by mir-16 and mir-143, cyclind1 was modulated by mir-16. 22260523_2 importantly, survivin was found to be targeted by mir-16, mir-143, mir-203. 22260523_4 as expected, mir-16 significantly suppressed the luciferase activity of bcl-2, cyclin d1, and survivin whereas mir-143 moderately inhibited luciferase activity of bcl-2 and survivin. 22260523_6 the data indicated that mir-143, mir-16 and mir-203 not only inhibited endogenous expression of bcl-2, cyclind1 and survivin, but also disturbed e2-induced upregulation of cyclin d1, an important cell cycle regulator, thereby, accounting for the impairment of cell proliferation. 26776318_1 collectively, these results indicate that mir-26a targets smad1 signaling in diabetic dermal wounds and that mir-26a neutralization restores ec growth and angiogenic function. 21321380_1 here we determined that mir-101 is down-regulated in gbm, resulting in overexpression of the mir-101 targetpcg protein ezh2, a histone methyltransferase affecting gene expression profiles in an epigenetic manner. 21321380_2 figure 2: mir-101 is down-regulated in gbm and target ezh2. 21321380_3 in conclusion, our results indicate that ezh2 has a versatile pro-tumoral function in gbm and that its overexpression is at least partly due to decreased mir-101 expression. 25578496_1 moreover, mir-145 suppressed smad3 by directly binding to the 3'-untranslated region of smad3. 25578496_2 these results show that smad3 is negatively regulated by mir-145 and a direct target of mir-145 in npc cells. 25578496_3 therefore, smad3 is a major target of mir-145 and involved in npc cell migration and invasion. 25578496_4 these data indicate that mir-145 affects metastasis by targeting smad3 in npc cells and tissues. 18701644_1 taken together, results above suggest that mir-16 family triggers an accumulation of cells in g0/g1 by regulating multiple down-stream efectors including ccnd1, ccnd3, ccne1 and cdk6 . 18701644_2 western blot analysis revealed that mir-16 and mir-424 markedly reduced ccnd1 protein levels compared to luc-sirna and mock transfected cells . 18701644_3 all the results above support the notion that mir-16 and mir-424 can regulate the expression of ccnd1 directly in vivo. 18701644_4 as evident from figure 4, mir-16 and mir-424 markedly reduced ccnd3, ccne1 and cdk6 protein levels compared with mock transfected cells . in contrast, we observed no decrease in cdc25a protein . 18701644_5 the results above indicated that mir-16 family regulated the expressions of ccnd3, ccne1 and cdk6. 18701644_6 the results of western blot displayed that mir-16 repressed the expression of ccnd1, ccnd3, ccne1 and cdk6 simultaneously, and each sirna inhibited its target respectively . 26885612_1 we predicted and experimentally validated mir-31 as a direct regulator of bap1. in conclusion, our results demonstrate that mir-31 directly recognizes and binds to the 3'-utr of the bap1 transcript and inhibits bap1 translation. 26885612_2 taken together, this study not only revealed a critical role for mir-31 as an oncogenic mirna in lung carcinogenesis but also explored the molecular mechanisms by which mir-31 contributed to lung cancer progression and identified bap1 as a direct target gene of mir-31. 23104180_1 western blotting combined with the luciferase reporter assay demonstrated that vegf-a was a direct target of mir-15a/16. 23104180_2 mir-15a and mir-16 affect the angiogenesis of multiple myeloma by targeting vegf. 23104180_3 vegf-a is a target of post-transcriptional repression by mir-15a and mir-16. 23104180_4 sequence alignment of human mir-15a and mir-16 with 3'-utr of vegf-a. 23104180_5 the seed sequence of mir-15a and mir-16 matches 3'-utr of vegf-a . 23104180_6 these data indicate an inverse correlation between the expression levels of mir-15a and mir-16 and the vegf-a protein levels. 23104180_7 the results indicated that vegf-a is an actual target of mir-15a and mir-16 in mm cells. 23104180_8 the data showed comparable steady-state mrna levels of vegf-a , providing evidence that mir-15a and mir-16 repressed vegf-a expression at the translational level. 23104180_9 these results further demonstrate that vegf-a is a major target of mir-15a/16 and the antiangiogenic effect of mir-15a is mainly through inhibition of vegf-a expression. 26464628_1 furthermore, transfection of mir-126 mimics decreased cadm1 expression in sgc-7901 cells at the protein levels , suggesting that cadm1 expression could be inhibited by mir-126. 26464628_2 together, these results suggested that cadm1 is a novel target of mir-126. 20878132_1 additionally, bcl-2, an important antiapoptotic molecule, was identified to be a novel direct target of mir-143, and the proapoptotic function of mir-143 is further suggested to be mainly through the targeting of bcl-2 expression. 20878132_2 these results demonstrate that endogenous bcl-2 expression is directly targeted and regulated by mir-143 and suggest that mir-143 may exert its proapoptotic function via inhibiting bcl-2 expression. 20878132_3 these results further confirm that endogenous bcl-2 is regulated by mir-143 expression. 20878132_4 since the bcl-2 stably overexpressed mg63 cells transcribed bcl-2 mrna without its 3'utr, mir-143 should no longer targetbcl-2 expression in these cells. 20878132_6 5b, mir-143 induced cell apoptosis was significantly decreased by bcl-2 stable overexpression. 20878132_7 these results confirm that the proapoptotic function of mir-143 is mediated by inhibiting its target the bcl-2. 19264608_1 demonstration of the conserved binding sites for these mirnas in the chicken p27 3'-untranslated region sequence and the repression of luciferase activity of reporter constructs indicated that mir-221 and mir-222 targetp27 in these cells. 19264608_2 in fact, it appears that this region is evolutionarily conserved across a diverse range of species, suggesting that the interaction between mir-221 and mir-222 with the 3'-utr may be a critical aspect in the regulation of p27 kip1 expression . 19490101_1 to investigate whether mir-23b targeted upa and c-met mrnas for degradation, a semiquantitative rt-pcr evaluation was carried out on rna isolated from control and transfected cells. 19490101_2 the data showed comparable steady-state mrna levels of upa and c-met , providing evidence that mir-23b in skhep1c3 cells can lead to decreased upa and c-met protein expression without affecting the amounts of their mrna. 19490101_3 in hela cells, the c-met 3'-utr was a targetthat was responsive to mir-23b , indicating that skhep1c3 rather than hela cells produce different molecules that may interact with the c-met 3'-utr. 23284895_1 luciferase activities of report vectors containing the 39utr of porcine bmp2 or mapk1 were downregulated by mir-378, which suggested that mir-378 probably regulated myogenesis though the regulation of these two genes. 23284895_2 the results of luciferase activities suggested that mir-378 could target the wild type 3' utrs of porcine bmp2 or mapk1, but not the mutation ones in which the binging sites were deleted. 23284895_3 these results suggested that mir-378 directly targeted the bmp2 and mapk1 3' utr, and might regulate myogenesis in the manner of acceleration of the differentiation and inhibition of proliferation . 23284895_4 micrornas may regulate multi-targets simultaneously, which was in accordance with our result that mir-378 could downregulate both bmp2 and mapk1 by recognizing their 3' utr. 21502362_2 the mrnas of sirt1 and sp1 contain putative binding sites for mir-22 in their 3'-utrs, and each site is broadly conservative among mammals. 21502362_3 cdk6 mrna contains three mir-22 binding sites in the 3'-utr, whereas it is different in conservation for each site . 21502362_4 these results provide experimental evidence that mir-22 can directly repress translation initiation of sirt1, sp1, and cdk6. 21502362_5 these findings indicate that mir-22 may affect the prb pathway of cellular senescence by targeting sirt1 and cdk6. 21502362_6 collectively, these findings suggest that sirt1, sp1, and cdk6 play an important role in mir-22-induced senescence. 17877811_1 we present evidence for the down-regulation of c-myc, one of the most potent and frequently deregulated oncogenes, by let-7 mirna, via the predicted bindsg site in the 3'utr, and verify the suppression of bcl-2 by mir16. 17877811_2 the sensor construct carrying the c-myc potential single bindsg site for let-7c appeared to be consistently well down-regulated by let-7 microrna. 17877811_9 to confirm further that cmyc oncogene is a real targetfor let-7c we performed next transfections of hela cells, using anti-let-7c inhibitor in order to block the predicted interaction of let-7c with our sensor constructs. 25907832_1 two binding sites for mir-494-3p at the 3'utr of pten mrna were identified with the rnahyb online program . 20299489_1 reporter gene assays identified mitogen-activated protein kinase kinase 1 as a direct target of mir-34a and c-fos as a direct target of mir-221/222. 22116552_1 we demonstrated that the protein phosphatase phlpp2, an important negative regulator of the pi3k/akt pathway, was a direct target of mir-17-92 mirnas, in addition to pten and bim.overexpression of mir-17-92 activated the pi3k/akt pathway and inhibited chemotherapy-induced apoptosis in mcl cell lines. 23762558_1 these results suggested that mir-149 inhibits foxm1 expression. 23762558_2 these data implied that mir-149 might inhibit emt by suppressing foxm1 expression in nsclc cells. 23762558_4 mir-149 negatively regulated emt by suppressing foxm1 expression. 23762558_7 our study found that overexpression of mir-149 or knockdown of foxm1 by shrna suppressed emt in nsclc cells, and mir-149 inhibited foxm1 expression. 23856509_1 real-time pcr analysis in colonic tissues from control and il-10 ko mice reveals a significant decrease of mir-124 and a significant increase of stat3 mrna levels in il-10 ko mice, relative to wt . 23856509_2 our analyses suggest that the mir-124/stat3 pathway is deregulated in both dss and il10-ko mouse models of colitis, consistent with our findings in human and in vitro studies. 23328512_1 mir-135b promoted gastric cancer cell proliferation, inhibited its apoptosis and directly regulated the expression of apc in gastric cancer cell. 22996586_1 mir-10a target the 3'-utr of the epha4 transcript and down-regulates its expression. 22996586_2 the eph tyrosine kinase receptor, epha4, was identified as the direct and functional targetgene of mir-10a. 22996586_3 our findings highlight the importance of mir-10a in regulating the metastatic properties of hcc by directly targeting epha4 and may provide new insights into the pathogenesis of hcc. in contrast, the reporter vector carrying the mutated epha4 3'-utr could restore egfp activity when this construct was cotransfected with mir-10a , indicating that mir-10a might suppress gene expression through the mir-10a-bindsg sequence in the 3'-utr of epha4. 22996586_4 taken together, our results suggested that mir-10a exerted its function by way of regulation of epha4 expression. 22996586_6 our research thus provides new insight into the mechanism of the pathogenesis of hcc and suggests that mir-10a and epha4 play an important role in cancerogenesis. 21460242_1 foxp1 was a direct target of mir-34a in a 3'-untranslated region -dependent fashion. 21460242_2 protein levels of foxp1 were also strongly reduced on the introduction of mir-34a into u2932 cells . in summary, our results show that foxp1 is a target of mir-34a and . 21851624_1 furthermore, we discovered that theexpression of bmi-1 was suppressed by mir-194 via direct binding to the bmi-13'-untranslated region 3'-utr. 21851624_2 mir-194 mrna expression was significantly lower in high bmi-1 expressing hec-50b-hi cells , showing that mir-194 level inversely correlated with bmi-1 expression. 21851624_3 these results collectively suggested a direct and specific inhibition of mir-194 on bmi-1 3'-utr in ec cells. 21851624_4 these results indicated that reexpression of mir-194 could reverse the emt phenotype, and dramatically decreased cell invasion in bmi-1 expressing ec cells. 25231273_1 expression levels of mir-29b, transforming growth factor --beta, alpha-smooth muscle actin and collagen i analyzed by rt-qpcr, western blot analysis and immunofluorescence staining following downregulation of mir-29b. 25231273_2 the results of mir-29b rt-qpcr revealed that the expression level of mir-29b was significantly lower in the downregulation group than in the negative control and blank control group , while there was no statistically significant difference between the latter 2 groups. 26475020_1 mir-132 interacts with the ago2 3'-utr. 26475020_2 mir-132 over-expression suppresses ago2 expression 23188821_1 and ccnj, a protein controlling cell mitosis, is down-regulated by mir-98 via targeting 3'-untranslated region of ccnj. 23188821_3 e, expression of ccnj was suppressed by mir-98 through 3'-utr. 21368858_1 to further determine whether the three remaining mirs were regulating ezh2, qrt-pcr was utilized to measure ezh2 mrna expression after transfection with mir-26a, 98, and 101. 21368858_3 as shown in figure 5e, overexpression of mir-26a or mir-98 reduced ezh2 protein expression, corroborating the biological effects of these two mirs in regulating ezh2 in npc. 21368858_4 mutating the seed region for mir-26a and mir-98 binding in the pmir-report-ezh2 utr vector completely abrogated its regulatory activity , thereby confirming that mir-26a and mir-98 directly interacted with the 3'-utr of ezh2. 22312705_1 mir-122 can specifically down-regulate the expression of bcl-2 and bcl-xl, and increase p53 activity in bel-7402/5-fu cells, which increased cells spontaneous apoptosis and sensitize cells to 5-fu. 21887328_1 by reporter luciferase assay, rt-pcr and western blot analysis, we also show that both mir-150 and mir-125b target p53. 21887328_2 taken together, these results confirmed the earlier observation that p53 is one of the targets of mir-125b . 21887328_3 thus, the increased expression level of endogenous p53 in sthdhq111/hdhq111 cells could be due to decreased expression of endogenous mir-125b. 21887328_5 moreover, over expression of pre-mir-150 decreased the endogenous expression of p53 in sthdhq111/hdhq111 cells as shown by western blot analysis . 21887328_6 these results indicate that p53 could be targeted by mir-150 as well. 21887328_7 thus, decreased expressions of mir-125b and mir-150 in sthdhq111/hdhq111 cells could result in increased expression of p53. 21887328_8 our investigation using hd cell lines provides important observations that mir-146a is regulated by p53 and rela/nfkb and increased p53 could be mediated through down regulation of mir-125b and mir-150. 26646104_1 taken together, we showed for the first time that mir-23b acts as a suppressor of emt in diabetic nephropathy through repressing pi3k-akt signalling pathway activation by targeting hmga2, which maybe a potential therapeutic target for diabetes-induced renal dysfunction. 20940405_1 interestingly, all mir-17 ~92 mimics tested decreased smad4 mrna levels, but this downregulation was most profound with mir-18a . 23389544_1 taken together, these experiments define hnf1b as a target of mir-802-dependent post-transcriptional silencing in liver in vitro and in vivo. 26338969_1 these results provided further evidence that slc30a1, serpinb2 and akr1c1 are respective bona fide target genes of mir-182 or mir-185 in human cells. 21962230_1 our data indicated that mir-185 directly interacted with the dnmt1 and the lower levels of mir-185 expression in glioma may be one of the reasons for the abnormal expression of dnmt1, which leads to aberrant dna methylation, contributing to the development of human glioma. 21962230_2 collectively, these data indicate that the down-regulated mir-185 expression is related to high levels of dnmt1 expression, which may be associated the development of glioma and support the notion that mir-185 directly target dmnt1 mrna, thereby regulating the expression of dnmt1 in glioma cells. 21962230_3 these data indicated that mir-185 directly interacted with the dnmt1 and the lower levels of mir-185 expression promoted the abnormal expression of dnmt1 in glioma. 23688833_1 mir-210 suppresses bnip3 to protect against the apoptosis of neural progenitor cells.the 23688833_2 over-expression of mir-210 decreased apoptosis in npcs, and the inhibition of mir-210 expression remarkably increased the number of tunel-positive npcs by 30% in response to hypoxia. 26653554_1 the correlation between mir-1290 and nfix expression was further examined by evaluating nfix expression in the human escc cell lines eca109 and kyse-410 after the overexpression and knockdown of mir-1290. 26653554_2 the overexpression of mir-1290 decreased the level of nfix mrna significantly and the knockdownof mir-1290 increased the level ofnfixmrna,inversely .theseresultsdemonstrated 26653554_3 that mir-1290 regulates nfix expression by decreasing the stability of mrna. 26653554_4 this finding suggested that the putative mirna binding sites of nfix was strongly responsible for this mirna-mrna interaction. 23124077_1 the direct target of mir-101, dna methyltransferase 3a , was identified in silico and validated using a 3'-utr reporter assay. 23124077_2 hbx -mediated mir-101 down-regulation and dnmt3a up-regulation supported the enhanced dna methylation of several tumor-suppressor genes in hbx-expressing cells. 26529121_1 further studies involving loss and gain of function confirmed that ncc specifiers like sox- 1 and sox- 9 are direct targets of mir- 200 and mir- 145 respectively and that they are essentially modulated by metformin. 26529121_2 taken together, our results confirm that metformin modulates mir- 200 and mir- 145 which directly target sox- 1 and sox- 9, the chief ncc determinants. 26529121_3 we also established for the first time that mir- 145 targets sox- 9 during nc development; and misregulation of sox- 9 was also witnessed in zebrafish. 25872451_1 smad7 and hoxd10 were downregulated in both sw480 and ht29 cells by mir-1269a . 25872451_2 western blot confirmed that mir-1269a suppresses smad 7 and hoxd10 protein levels . 25872451_3 therefore, mir-1269a directly targets smad7 and hoxd10 through the identified binding sites in their 3'-utr. 21423181_1 this coincided with sequestration of mir-21 in a slower-migrating heteroduplex with antimir-21, de-repression of hela mrnas with canonical mir-21 seed match sites and upregulation of the pdcd4 target protein31 . 25982393_1 more recently, we have reported that microrna-296-5p was identified to play a tumor suppressive role by targeting the 3'-utr of pin1 mrna of prostate cancer . in addition, mir-296-5p was recently found to be progres sively lost during tumor progression in various cancers, including crc . 25982393_2 to understand the correlation between mir-296-5p and pin1 in crc, we first analyzed the expression levels of pin1 protein and mir-296-5p in crc cell lines by western blot and quantitative rt-pcr analysis. 25982393_5 these results are consistent with our previous study showing that mir-296-5p playing a tumor-suppressive role by targeting pin1. 26758433_1 the correlation between mir-143 and fam83f expressions was further examined by evaluating fam83f expression in the human escc cell lines after the overexpression and knockdown of mir-143. 26758433_2 this finding suggests that the putative mirna binding sites of fam83f were responsible for this mirna-mrna interaction. 26758433_3 these results demonstrated that mir-143 regulates fam83f expression by decreasing the stability of mrna. 22474262_1 spot42, ryhb, and rybb regulate sdhc expressionpost-transcriptionally. 25135862_3 we found that protein levels of smarca4 and mst1 decreased significantly in cells transfected with mir-199a-5p mimic compared to cells transfected with scramble . 25135862_4 western blot showed that mst1 levels are positively correlated with the increasing concentration of mir-199a-5p inhibitor, further indicating that mst1 is a target of mir-199a-5p. 25135862_5 our western blots and luciferase reporter assays confirmed that smarca4 and mst1 are directly regulated by mir-199a-5p at the posttranscriptional level. 15466019_1 micc could potentially form base pairs with the ompc mrna, suggesting that it may act as an antisense regulator. 15466019_2 since the micc and ompc genes are located at different genetic loci and are produced from two separate transcriptional units,the situation strongly mimics the micf regulation of ompf. 15466019_4 these similarities encouraged us to test the hypothesis that micc regulates ompc expression. 22048026_1 among many mirnas that are predicted to target htt, we showed using various experimental approaches that mir-214, mir-150, mir-146a and mir-125b could target both human htt and mouse htt. 22048026_6 taking together, we showed that mir-214, mir-150, mir-146a and mir-125b targeted htt. 26797246_1 to investigate if crtc1 is a target of mir-212/mir-132 in insulin-secreting cells we overexpressed the micrornas and measured the expression of crtc1. 26380016_1 reporter assays confirmed the direct binding and repression of mir-23 to the 3'-utr of vegf mrna. 26380016_2 mir-23 regulates epc function via targeting vegf. 26380016_3 generally speaking, our research disclosed mir-23 suppresses epc activities in cad patients via targeting vegf. 25281924_5 using a bioinformatics method, we further show that cdk9 is a direct target of mir-874 and that its protein level is negatively regulated by mir-874. 25281924_6 therefore, the data reported in this manuscript demonstrate that mir-874 is an important regulator in breast cancer and imply that the mir-874/cdk9 axis has potential as a therapeutic target for breast cancer. 22846677_1 because premir-203 reduced plaa expression during sp exposure, these data confirm the interaction between mir-203 and plaa mrna. 22846677_2 mir-203 may regulate expression of the novel nociceptive mediator plaa after incision. 22846677_3 expression of plaa after sp exposure in rek cell line identifying plaa as a direct target of mir-203. 22327366_1 mock- or klf2-transduced huvecs were co-cultured with untreated smcs for 24 h and the expression levels of elk1 , klf4 and camk2d , cfl1, phactr4 and ssh2 and mmp3 were analysed by real-time pcr . 22327366_2 mouse endothelial cells were isolated from wild-type or mir-143/145-deficient mice and were incubated with smcs. 22108519_1 mature mir-143 and mir-145 are coordinately expressed, and both directly targetthe pai-1 3'utr, leading to reduced pai-1 mrna and protein levels. 22108519_2 thus, the direct comparison of mirna and mrna levels in tissue samples, and to some degree in cell lines, confirm that expression of pai-1 and mir-143/-145 are mutually exclusive. 22108519_3 however, downregulation of pai-1 expression by mir-143 and -145 was also confirmed in other cancer cell lines, including h1299 , hela and u251 , thereby demonstrating that mir-143/-145-directed repression of pai-1 is not restricted to bladder cancer . 22108519_4 plasminogen activator inhibitor-1 mrna was significantly enriched upon mir-143 and -145 transfection compared with negative controls, suggesting direct interaction between mir-143/-145, risc complexes and pai-1 mrna . 20427544_1 therefore, mir-155 target smad1 and smad5 through binding to their respective predicted mir-155 target sites in their 3'-utrs. 20427544_2 to determine whether endogenous smad1, smad5, hivep2, cebpb, or myo10 genes are regulated by mir-155, quantitative rt-pcr analysis was carried out in retrovirally transduced mutu i cells. 20427544_3 expression levels of smad1, smad5, hivep2, cebpb, and myo10 were found to be lower in cells transduced with the mir-155 retrovirus . 20427544_4 further, smad1 and smad5 protein levels were lower in mir-155-transduced mutu i cells . 26206264_1 ppara and e-cadherin as direct downstream targets of mir-10 in hcc. 19578724_1 in this study, we confirmed that bone morphogenetic protein receptor ii is a direct target of mir-21, and also showed that the protein level of bmprii correlates inversely with the amount of mir-21 in pc3 and lncap cells. 19578724_2 these data suggest that mir-21 could regulate the expression of bmprii by binding to not only the two downstream conserved binding sites but also the two upstream predicted binding sites. 19578724_3 taken together, these results confirmed that bmprii is regulated by mir-21. 26595523_1 further studies identify metadherin as a direct target gene of mir-630. 26595523_2 herein, we report that mir-630 is significantly suppressed in human breast cancer specimens and cancer cell lines, and the mirna suppresses breast cancer progression by targeting metadherin . 26595523_3 overall, these results suggested mtdh was the potential functional target gene of mir-630. 21656380_1 our findings showed that, when either of two binding sites in the 3'-utr of the e2f1 gene was mutated, the regulation of e2f1 by mir-106a was completely eliminated. 21656380_2 taken together, these data confirmed that e2f1 is a direct target of mir-106a. 21656380_3 our results showed e2f1 induction can rescue the tumorsuppressive effects of mir-106a overexpression , indicating that e2f1 is a functional target of mir-106a. 21656380_4 therefore, the tumor-suppressive effects of mir-106a are regulated through the regulation of e2f1. 21656380_5 these indicated that mir-106a controls e2f1 levels by translational suppression rather than by mrna degradation. 21656380_6 therefore, it supported our hypothesis that mir-106a regulates p53 expression via the inhibition of e2f1. 21355095_1 kip1 ubiquitination-promoting complex 1, suppressor of cytokine signaling 1, and cd115 were functional target of mir-155. 21355095_2 consistent with this, silencing of mir-155 in mdcs resulted in increased socs-1 expression at protein level , whereas forced expression of mir-155 led to reduced socs-1 expression in imdcs . in addition, kpc1 expression was reduced along with mir-155 up-regulation during dc maturation . 21355095_3 taken together, these results demonstrate that mir-155 indirectly regulates p27kip1 expression by targeting kpc1. 21355095_4 these results suggest that cd115 is a direct target of mir-155. 25817558_1 while mir-221 was identified as a suppressor of hdac6 by ectopic expression of mirna mimics in dicer knockdown cells, targeted-disruption of mir-221 repressed cancer cell growth through derepressing hdac6 expression. 25817558_2 from the comprehensive mirna expression analysis of hcc tissues paired with adjacent non-cancerous hepatic tissues, mir-221 was identified to repress endogenous hdac6 expression in hcc cells. 25817558_3 taken together, the results show that jnk stimulated by hgf led to c-jun activation and the transcriptional activation of mir-221, which elevated mir-221 expression playing a critical role in suppressing hdac6 in hcc cells. 26062664_1 snai1 is identified as a functional target of mir-153 and is downregulated in pdac specimens. 26062664_2 to further demonstrate that snai1 was directly targeted by mir-153 in pdac cells. 26062664_3 thus, our data strongly suggested that snai1 is a target of mir-153 in pdac. 21880154_1 remarkably, we found that the tumor suppressor bak1 had the most reduced activity, which suggested that bak1 was likely to be an important target regulated by mir-125b in leukemia. 21880154_2 this finding demonstrates that bak1 is a target of mir-125b in leukemic cells and that the putative mir-125b binding site is critical for mir-125b regulation of bak1 expression. 21880154_3 these results strongly suggest that bak1 is a target of mir-125b in pediatric apl. 21880154_4 furthermore, we inferred that mir-125b directly regulates bak1 expression, thereby modulating the susceptibility of leukemic cells to apoptosis. 22684007_2 these findings suggest that down-regulation of mir-376a may contribute to the development of hcc by targeting p85alpha. 22684007_4 as shown in fig.3e, the mir-376a mimics repressed the luciferase activity of the wild type plasmid but not the mutant plasmid , indicating that pik3r1 is a direct target of mir-376a. 22684007_5 taken together, these observations suggested that decreased expression of mir-376a triggered up-regulation of pik3r1 partially in hcc. 20683643_1 in hela cells, mir-200b directly reduced the expression of rnd3 at the mrna and protein levels, which thereby promoted expression of the downstream protein cyclin d1 and increased s-phase entry. 20683643_2 luciferase assays revealed that overexpression of mir-200b could significantly reduce luciferase activity from the reporter vector containing the 3' utr of rnd3. 20683643_3 our results suggest that mir-200b regulates rnd3 expression by targeting both putative targetsites 1 and 2 . 20683643_4 we conclude that mir 200b can directly regulate the expression of rnd3 in vivo . 20683643_5 our results suggest that mir-200b regulates ccnd1 expression and promotes cell cycle progression by targeting rnd3 . 23447608_1 figure 5. mir-195 downregulates the expression of app and bace1 proteins. 23447608_2 figure 4. app and bace1 are potential targets of mir-195. 26054690_1 mir-217 targeted wnt5a in os cells. 26054690_2 mir-217 suppressed the transcription activity of the wnt5a gene by targeting the binding site in the 3'-utr of wnt5a mrna. . 26054690_3 mir-217 suppressed cell progression by targeting wnt5a. 25474084_1 the present study explored the role and mechanism of mir-222 in increasing the expression of p53 up-regulated modulator of apoptosis and enhancing the sensitivity of oscc to cisplatin 25355277_1 pre-treatment with isdn reversed the decrease in mir-130b expression induced by hg stimulation , but had no apparent effect on mir-130a expression . 25355277_2 furthermore, inhibition of the erk/foxm1 pathway by either pd98059 or foxm1 sirna substantially abolished the recovery of mir-130b expression following pre-treatment with isdn. 25355277_3 erk phosphorylation and foxm1 activity were examined following the downregulation of mir-130b, indicating that there were no signficant changes between the control group and the antagomir group, both in phosphorylated erk and in foxm1 expression.mirna-130b 22899845_1 here, we have identified a novel heart-andmuscle-specific microrna, mir-92b, which is activated by mef2 and subsequently downregulates mef2 through binding to its 3'utr, forming a negative regulatory circuit that fine-tunes the level of mef2. 22899845_2 mir-92b negatively regulates mef2 levels in vivo. 22899845_3 mir-92b negatively regulates mef2 through binding to conserved mir-92b targeting sites on mef2 3'-utr. 22899845_4 mutation of the mir-92b targeting sites in the mef2 3'-utr largely abolished this inhibition , suggesting that mir-92b inhibits mef2 expression through binding to the two conserved mir-92b targeting sites. 22899845_5 these results indicate that the mir-92b sponge could efficiently compete with the endogenous mir-92b targeting sites, including the ones in mef2 3'-utr, and subsequently release the inhibition of mef2 expression caused by mir-92b. 22899845_6 these rescue experiments suggest that one essential role of mir-92b is to regulate mef2 levels. 22194984_2 luciferase assays and western blot analysis demonstrated that the mir-200b/200c/429 family recognized the mre in the 3' utr of ap-2alpha gene and negatively regulated the expression of endogenous ap-2alpha proteins. 26687115_1 amongst these, fzd3, fzd5, dvl3, frat2, and ck2a2 were validated as direct targets of the mir-29 family. 26651881_1 we also discovered that the effects of mir-21 on hasm cells depended on pten expression. 26651881_2 overexpression of mir-21 is directly related to the decrease of pten expression in hasm cells. 26651881_3 mir-21 significantly downregulated the expression of pten in the hasm cells and the low expression of pten depended on the level of mir-21. 25094038_1 mir-106b reduces tgf--beta type ii receptor expression during emt. 25094038_3 4c and d, tgf--beta1 induced expression of tgf--beta type ii receptorin hk-2 cells undergoing emt, whereas enhancement of mir-106b expression inhibited the expression of tgf--beta type ii receptor . 25094038_4 these data suggest that the inhibitory effects of the mir-106b-25 cluster in tgf--beta1-induced emt of hk-2 cells may be due to the reduced activity of tgf--beta signaling and the associated decrease in expression of tgf--beta type ii receptor. 22450326_1 we further identified that mir-25 directly targeted cdh1 3'-untranslated region and repressed the expression of cdh1. 22450326_2 these results, for the first time, demonstrate that mir-25 promotes escc cell migration and invasion by suppressing cdh1 expression. in addition, we uncovered an inverse correlation between mir-25 and cdh1 in escc cell lines. 22450326_3 furthermore, cdh1 reversing cell migration and invasion induced by mir-25 overexpression indicated that cdh1 functioned as a mediator of mir-25 in cell migration and invasion. 22450326_4 our study indicates that mir-25 inhibits the translation of cdh1 mrna by targeting its 3' utr, which adds a new explanation of deregulation of cdh1 expression in escc. 22508046_3 the expression pattern was inversed with mir-206, indicating that mir-206 might regulate otx2 expression in vivo. 25844955_1 in addition, ch3, but not ch1 and ch2, significantly reduced tumor necrosis factor alpha-搒timulated expression of the mir-126 target vcam-1 to a similar extent as mir-126-3p mimic transfection . 26531758_1 smad7 was confirmed to be a direct target of mir-21, by luciferase reporter and western blot assays. 26531758_2 figure 2. mir-21 regulates the smad7 protein level by inhibiting translation. 26531758_3 thus, smad7 is a functional target of mir-21 whose upregulation promotes egf -induced breast cancer cell invasion and migration. 20859956_1 furthermore, we detected the downregulation of the protein level of cyclin g1 with mir-122a overexpression . 20859956_2 cyclin g1 was the known target of mir-122a . 25731730_1 timp2 mrna 3'-utrs depicting target binding sites for mir-221/222. 25731730_2 these results further suggested that timp2 is a direct target of mir-221/222 and that mir-221/222 promote glioma cell invasion and angiogenesis, at least in part by inhibiting timp3 expression. 21752897_1 interestingly, a significant decrease in cxcr4 mrna level was observed in the cells transfected with the mir-1 with respect to the scrambled oligonucleotide , whereas sdf-1alpha mrna expression levels are unchanged , indicating that mir-1 affects cxcr4 protein synthesis by facilitating the specific degradation of cxcr4 mrna. 21752897_2 we also show that mir-1 transfection down-regulates the luciferase activity of a reporter construct carrying the 3'-utr-cxcr4 or 3'-utr-sdf-1alpha sequence , and the mutation in the putative 3'-utr site inhibits the sensitivity of the reporter constructs to mir-1. 21752897_4 fig. 3. cxcr4 and sdf-1alpha are targets of mir-1. 21752897_5 a and f, schematic representation of the 3'-utr sites of the cxcr4 and sdf-1alpha genes targeted by mir-1. 21752897_6 fig. 4. cxcr4 and sdf-1alpha protein expression is inversely correlated with mir-1 expression in goiter , fa, ftc, ptc, and atc tissues. 24384130_1 furthermore, by using luciferase assays, we found that both overexpression and inhibition of mir-125b induced a significant change of vegf-a luciferase activity , which demonstrated that vegf-a is also a direct target of mir-125b in biliary epithelial cells. 24384130_2 we found that, after knockdown of mir-125b, there is an increase in hdc expression compared with control-transfected cells . 22363487_2 4, the mir-34a precursor dramatically decreased the expression of notch1 and jagged1 protein and mrna, while there were no effects of mir-34a on notch2 protein and mrna levels. 22363487_3 the protein levels of notch1 and jagged1 were suppressed more than the mrna levels by mir-34a transfection, implying that mr-34a regulated the expression of notch1 and jagged1 at the post-transcriptional level. 22363487_4 the results showed that snail protein expression was suppressed by mir-34a transfection. 22363487_5 these data indicate that mir-34a directly interacts with the 3'utr of notch1 and jagged1, but not with notch2. 26141986_1 met was found to be a target for mir-449c . 26141986_3 the intact 3- utr of met was cloned into luciferase reporter plasmids, which were used for co-transfection with mir-449c or as-mir-449c into snu~ 5 cells. 26141986_4 we found that mir-449c significantly reduced the luciferase activity of the 3- utr reporter for met, while as-mir-449c significantly increased the luciferase activity of the 3'-utr reporter for met. the mir-449c-mediated changes in met transcript levels were further found to alter protein levels . 26141986_5 thus, our data suggest that mir-449c may function at least partially via met. 26617770_1 luciferase reporter assay demonstrated that mir-133b could directly target egfr. 26617770_2 altogether, our results indicated that mir-133b overexpression was shown to inhibit proliferation and invasion of oc cells through suppression of the mapk and pi3k/akt signaling pathways by targeting egfr. 25073510_2 mir-144 acts as a tumor suppressor in some malignancies, while its role in hcc is unclear. 25073510_5 e2f transcription factor 3 was identified as a target of mir-144 in hcc cells. 25073510_6 moreover, e2f3 overexpression partially attenuated the tumor suppressive effects of mir-144, and the expression of e2f3 was negatively correlated with mir-144 level in hcc tissues. 25073510_7 our data suggest that mir-144 might suppress the growth and motility of hcc cells partially by targeting e2f3. 21339227_1 mir-124a directly binds to the 3'-untranslated region of cyclin-dependent kinase 2 and monocyte chemoattractant protein 1 mrna, and the induction of mir-124a in ra synoviocytes significantly suppressed the production of the cdk-2 and mcp-1 proteins. 21339227_2 subsequent luciferase assays showed that mir-124a specifically suppressed the luciferase activity driven by the 3'-utr of mcp-1 mrna. 21339227_3 a luciferase reporter assay demonstrated that mir-124a specifically suppressed the reporter activity driven by the 3'-utr of cdk-2 mrna but not reporters driven by the mutant of 3'-utr of cdk-2 mrna. 21339227_4 we also found that cdk-6 protein, another cdk that regulates the g1-s phase, was suppressed by mir-124a. 23087182_1 our data point toward an important role for mir-20a in the regulation of pro-inflammatory cytokines release, by controlling ask1 expression in ra fls. 23087182_2 altogether, these data suggest that ask1 mrna is a conserved direct target for post-transcriptional regulation by mir-20a. 23087182_3 these results indicate that mir-20a regulates the expression of ask1 at the translational level. 26461474_1 this suggests that kdm2a, kdm4a, kdm5b, kdm7a and med1 are direct targets of mir137. 19318487_4 microarray and bioinformatic analysis identified the novel oncogene macrophage migration inhibitory factor as a potential target of mir-451. in fact, overexpression of mir-451 down-regulated mrna and protein levels of mif and decreased expression of reporter genes with mif target sequences. 19318487_5 moreover, we found a significant inverse correlation between mir-451 and mif expression in tumoral gastric biopsies. 22185353_1 accordingly, over-expression of mir-16 could significantly suppress the luciferase activity of reporter fusion with the binding sites of tnfalpha in its 3'utr region, suggesting that mir-16 played its role in lps-induced lung inflammation by a direct manner. 22185353_2 it has been previously reported that mirna regulates the expression of the targetmrnas by binding its 3- utr , thus, the 3- utr of either il-6 or tnfalpha was cloned into psicheck2 vector, and the results showed that over-expression of mir-16 could significantly suppress the luciferase activity of reporter fusion with the binding sites of tnfalpha in its 3'-utr region, but that it could not suppress that of il-6 , suggesting a direct action of mir-16 in lps-induced lung inflammation. 23780685_1 luciferase activity assay showed that mir-181a mimics inhibited bcrp expression by targeting the 3' untranslated region of the bcrp mrna. 23780685_2 these findings suggest that mir-181a regulates bcrp expression via binding to the 3' -utr of bcrp mrna. 23780685_3 importantly, our study revealed that mir-181a, functioning as a bcrp suppressor, reversed bcrp-mediated drug resistance in vitro and in vivo. 23780685_4 compared with the negative control, mir-181a mimics significantly inhibited luciferase activity in mcf-7/mx cells , suggesting that the 3' -utr of the bcrp mrna is a target site of mir-181a. 23780685_5 the expression of bcrp, but not mrp, pgp, and lrp was significantly decreased in cells transfected with mir-181a mimics,comparedto cells transfected with negative controls. 23780685_6 , suggesting that mir-181a negatively regulated endogenous bcrp expression. 22301781_1 to further confirm the specificity of 3'-utr sequences targeted by mir-16 and mir-195, luciferase reporter constructs containing mutant 3'-utr were constructed . 22301781_2 luciferase reporter gene activity of these mutants was not affected by overexpression of mir-16 or mir-195 . 22301781_3 these data indicate that mir-16 and mir-195 directly associated with the 3'-utr of mapk8, ccne1, andcdc6 to repress their protein expression. 22301781_4 we observed that suppression of mir-16 and mir-195 clearly increased expression of mapk8, ccne1, and cdc6 , although its effect on brdu incorporation was not clear . 22301781_5 further studies are needed to demonstrate whether or not mapk8, ccne1, and cdc6 are sufficient targets of mir-16 and mir-195 to induce cell proliferation by mediating tsh action. 21548929_1 collectively, our results demonstrate that mir-196a is a bona fide negative regulator of nobox during bovine early embryogenesis. 21548929_2 figure 1 prediction of a mir-196a binding site in the 3' utr of bovine nobox mrna. 21548929_3 thus, the inverse relationship between mir-196a and nobox expression/activity supports the proposed role of mir-196a as a physiological regulator of nobox during early embryogenesis. 21548929_4 these results unequivocally show that bovine nobox is regulated at the post-transcriptional level by mir-196a and further supports the hypothesis that mir-196a is responsible for the negative regulation of nobox. 21548929_5 these data indicate the predicted mre is critical for the direct and specific binding of mir-196a to nobox transcript. 21548929_6 thus, a similar mechanism is likely to be involved in the mir-196a negative regulation of nobox expression in bovine embryos during met. 22565577_1 functional mir-29 binding to pdgf-c and igf-i mrna sequences, but not to the corresponding mutants, was then proven by reporter assays. 22565577_2 our mir-29 binding studies and expression data of mir-29-treated hsc clearly demonstrated that the growth factors pdgf-c and igf-i were tightly regulated by mir-29. 22565577_3 interaction of mir-29 with the 3'-untranslated region of platelet-derived growth factor -c, insulin-like growth factor -i. specific mir-29 interaction to the 3'-utr of pdgf-c and igf-a transcripts. 22565577_4 pdgf-c and igf-i: novel target of mir-29. 26841847_1 these results indicated that vhl is a direct target of mir-101. 26841847_3 4f, mir-101 significantly suppressed vhl protein levels in both cell lines and this suppression was through post-transcriptional regulation because mir-101 over-expression did not reduce vhl mrna levels 21501346_1 this indicates that arrs could pair with the gade mrna t3 at 312-380 nucleotides upstream from the start codon. 22745315_1 studies of let-7 deletion indicated that the transcription factor encoded by abrupt is a key direct target , as abrupt is misexpressed in let-7 clones and abrupt heterozygosity can suppress certain let-7 mutant phenotypes. 22745315_2 we used a genetic assay to confirm that the 3' utr of abrupt can be directly repressed by let-7. 21834602_1 the anti-apoptosis gene bcl-2, a putative target mrna that can be downregulated by mir-16, was expressed in bmpcs from al patients, despite elevated levels of mir-16. 26546590_1 in transfection studies, mir-422a was found to directly target kallikrein-related peptidase 4 mrna. 26546590_3 together, klk4 may be a direct target of mir-422a. 18794355_5 tgf-beta induces mir-155 expression and promoter activity through smad4. 18794355_7 further, the ectopic expression of mir-155 reduced rhoa protein and disrupted tight junction formation. 18794355_8 reintroducing rhoa cdna without the 3' untranslated region largely reversed the phenotype induced by mir-155 and tgf-beta. 18794355_10 these data suggest that mir-155 may play an important role in tgf-beta-induced emt and cell migration and invasion by targeting rhoa and indicate that it is a potential therapeutic target for breast cancer intervention. 21294122_1 our data show that mir-34a regulates myc through direct binding to its 3'utr. 18931683_1 we report that the mir-15a and mir-16-1 cluster targets ccnd1 and wnt3a, which promotes several tumorigenic features such as survival, proliferation and invasion. 18931683_2 in cancer cells of advanced prostate tumors, the mir-15a and mir-16 level is significantly decreased, whereas the expression of bcl2, ccnd1 and wnt3a is inversely upregulated. 18931683_3 delivery of antagomirs specific for mir-15a and mir-16 to normal mouse prostate results in marked hyperplasia, and knockdown of mir-15a and mir-16 promotes survival, proliferation and invasiveness of untransformed prostate cells, which become tumorigenic in immunodeficient nod-scid mice. 18931683_4 conversely, reconstitution of mir-15a and mir-16-1 expression results in growth arrest, apoptosis and marked regression of prostate tumor xenografts. 18931683_5 altogether, we propose that mir-15a and mir-16 act as tumor suppressor genes in prostate cancer through the control of cell survival, proliferation and invasion. 26073258_1 pi3k-c2b is a target of mir-362-5p in sh-sy5y cells. 26073258_2 suggested that mir-362-5p might negatively regulate the expression of pi3k-c2b in vivo 22182733_1 microrna-20a target the pro-apoptotic prolyl hydroxylase protein egln3/phd3. 22182733_2 moreover, previous experiments in non-cardiomyocytes have also implicated the e2f family of transcription factors as potential target of mir-20a . 22182733_4 using the luciferase-3- utr approach, we could confirm significant targeting of e2f1 as well as e2f2 by mir-20a . 22182733_5 consistently, adenovirus-mediated overexpression of mir-20a markedly suppressed e2f1 and e2f2 expression in cardiomyocytes . 22182733_6 taken together, direct targeting of egln3 as well as e2f1 by mir-20a provides a potential mechanism for the observed antiapoptotic effects. 26872615_1 dual-luciferase reporter assay showed that mir-23b bound with the 3- untranslated region of ccng1. 26872615_2 our previous study showed that mir-23b was highly expressed in normal ovarian tissues than ovarian carcinoma tissues, and our predicted seed region in the 3- untranslated regions of ccng1 revealed that it's a target of mir-23b, thus we investigated the involvement of ccng1 and mir-23b in ovarian cancer for the first time. 26872615_3 the predicted seed region in the 3- untranslated regions of ccng1 revealed that it is direct target of mir-23b ; dual-luciferase reporter assay indicated that mir-23b significantly decreased the relative luciferase activity of the wild-type ccng1 3- utr as compared with the mutant ccng1 3- utr, indicating that mir-23b may directly bind to the 3- utr of ccng1 . 20023696_1 suppression of cxcr4 by kshv and k13 was associated with upregulated expression of mir-146a, a microrna that is known to bindto the 3'-untranslated region of cxcr4 mrna. 20023696_2 a recent study demonstrated that mir-146a downregulates the expression of cxcr4 in k562 cells by binding to two sites in its 3'-utr . 20023696_3 to examine the hypothesis that kshv might suppress cxcr4 expression via mir-146a, we used qrt-pcr analysis to examine the effect of kshv infection on mir-146a expression in huvecs. 20023696_4 we observed a significant upregulation of mir-146a expression in huvecs at 6, 12, and 48 h after kshv infection, as reflected by decline in the corresponding deltact values . 20023696_5 taken collectively, the above results demonstrate that kshv and k13 downregulate cxcr4 expression by upregulating mir-146a. 20023696_6 taken collectively, these results suggest that kshv-mediated upregulation of mir-146a and downregulation of cxcr4 that we demonstrated in vitro also occur in vivo. 26415732_1 atp8a1 identified as a direct target of mir-140-3p in nsclc cell. 26415732_2 the atp8a1 gene directly targeted by mir-140-3p. 26857067_1 endoglin mrna was a direct target of mir- 342- 5p 26838466_1 the overexpression of mirna-205 in granulosa cells and reporter gene assay shows that the marker gene ptx3 for cumulus expansion is the putative target gene of mir-205. 26838466_2 our data provide evidence that the bdnf-induced maturation of oocytes in pigs may be mediated by mir-205 through the regulation of potential target gene, ptx3. 26838466_3 the mir-205 negative control had no significant effect on the reporter luciferase activity, indicating that mir-205 interacted directly with the 30 utr of ptx3 . 26811318_1 over-expression of the wt sdsr significantly decreased the tolc mrna containing the wt leader sequence, confirming the negative regulation observed in the tolc-lacz fusion . 17660297_1 taken together, these data reveal that human cholangiocytes express multiple endogenous mirnas, including members of the let-7 family, which have complementarity to tlr4 mrna, and that modulation of at least one of these, let-7i, can mediate tlr4 protein expression in cholangiocytes in vitro. 17660297_2 to test whether let-7i can induce cleavage of tlr4 mrna, we measured the mrna level of tlr4 in cultured cholangiocytes transfected with either let-7i antisense 2-methoxy oligonucleotide or let-7i precursor by quantitative rt-pcr. 17660297_3 no significant difference of tlr4 mrna was found in cells transfected with either let-7i antisense 2-methoxy oligonucleotide or let-7i precursor . 17660297_4 to directly address whether let-7i binds to the 3'-utr of tlr4 mrna resulting in a translational suppression, we generated a pmir-report luciferase construct containing the tlr4 mrna 3'-utr with the putative let-7 binding site . 17660297_5 taken together, the above data suggest that the seed region for let-7 binding within the tlr4 3'-utr is critical for tlr4 translational regulation in h69 cells. 17660297_6 furthermore, manipulation of cellular levels of let-7i results in alterations of tlr4 protein expression by suppressing translation via interactions with the 3'-utr of tlr4 mrna rather than mrna cleavage. 23013439_1 these results collectively indicate that mir-101 may function as a tumor suppressor in gastric cancer, with cox-2 as a direct target these data collectively suggest that mir-101 overexpression in gastric cancer cell lines inhibits cox-2 mrna and cox-2 expression. 23013439_3 the alignment of mir-101 with its putative targetsequences on the human cox-2 3'-utr is shown in fig.2a. 23013439_4 previous studies have also demonstrated, by luciferase activity assay, that mir-101 interacts directly with the 3'-utr of cox-2 mrna, leading to its post-transcriptional repression . 23013439_5 our bioinformatics analysis has revealed that the 3'-utr of human cox-2 mrna has a complementary site for the seed region of mir-101. 23013439_6 these data collectively indicate that mir-101 can effectively reduce tumor growth by suppressing cox-2 expression in vivo. 25672607_1 the above data demonstrated that hbp1 is a genuine target of mir-155. 26845645_2 these results demonstrated that mir-450b-5p directly bound to the 3'-utr of sox2 and inhibited its expression. 26845645_3 furthermore, mir-450b-5p directly targeted sox2. 10491431_1 expression of the sf/hgf and c-met genes was inhibited by transfecting glioblastoma cells with chimeric transgenes consisting of u1 small nuclear rna, a hammerhead ribozyme, and antisense sequences. 22310293_1 taken together, our data indicate that hur and dicer1 are bona fide targets that are repressed in chl cells by endogenous mir-9. 22310293_2 hence, the direct regulation of hur by mir-9 is reflected in the transcriptome following mir-9 inhibition, suggesting that a large proportion of the effects seen in the arrays upon mir-9 inhibition were hur-mediated. 22310293_3 taken together, our data show that hur and dicer1 are targeted by mir-9 in vivo during chl tumorigenesis and that pharmacological inhibition of mir-9 by a seed-targeting tiny antimir leads to significantly reduced tumour outgrowth in a mouse model of chl. 22407310_1 mir-200c has two positions which are connected with zeb1 3'-utr. 22407310_2 mir-200c inhibits invasion and migration in human colon cancer cells sw480/620 by targeting zeb1. 22407310_3 taken together, our study demonstrated that mir-200c inhibits metastatic ability by targeting zeb1 in colon cancer cells sw480/620 and suggested that modulation of mir-200c with inhibitors or mimics could serve as therapeutic tool for inhibiting metastasis in colorectal cancer. 22407310_4 overexpression of mir-200c leads to translational inhibition of zeb1 which induces emt in cells. 22407310_5 these data provide further evidence that mir-200c can regulate the expression of zeb1 in mrna level. 26527888_1 besides, we identify that raf1 is a direct target of mir-15a/b, mir-16, and mir-195 by dual luciferase reporter assay. 26527888_2 in this study, we show for the first time that raf1 is upregulated in thyroid cancer and identified that raf1 is a target gene of mir-15a/b, mir-16, and mir-195. 26527888_3 while there is no significant difference when cotransfected with the raf1 deletion utr , indicating mir-15a/b, mir-16, and mir-195 can directly bind to the 3'-utr of raf1 mrna. 26527888_4 further luciferase report assay confirms that raf1 is a target gene of mir-15a/b, mir-16, and mir-195 . 26527888_5 these data indicate that raf1 is a direct target of mir-195 in thyroid cancer cells, and mir-195 can regulate the expression of raf1 by inhibiting protein translation. 23250910_1 further studies have identified the e-cadherin transcription repressor slug as a direct target gene of mir-124; its downregulation by mir-124 increases the expression of e-cadherin, a hallmark of epithelial cells and a repressor of cell invasion and metastasis. in addition, the overexpression of mir-124 determines the epithelial phenotype of breast cancer cells, by targeting the emt regulator slug. 18493594_1 in vitro or in vivo treatment with antagomir-17-5p abolishes the growth of mycn-amplified and therapy-resistant neuroblastoma through p21 and bim upmodulation, leading to cell cycling blockade and activation of apoptosis, respectively. 23337504_1 ectopic expression of mir-330 down-regulated cdc42 expression at both protein and mrna level, mimicked the effect of cdc42 knockdown in inhibiting proliferation, inducing g1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of cdc42 could partially attenuate the effects of mir-330. in addition, elevated expression of mir-330 could suppress the immediate downstream effectors of cdc42 and inhibit the growth of colorectal cancer cells in vivo. 23337504_2 to sum up, our results establish a role of mir-330 in negatively regulating cdc42 expression and colorectal cancer cell proliferation. 23337504_3 they suggest that manipulating the expression level of cdc42 by mir-330 has the potential to influence colorectal cancer progression. 22749944_1 mir-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting gstp1. 22749944_2 luciferase reporter assay proved that gstp1 was a targetgene of mir-513a-3p, which was confirmed by western blot analysis. 22749944_3 and it indicated that mir- 513a-3p could complementarily bindto the 3'-utr of human gstp1 gene. 25510666_1 after prediction with online software, we further used dual-luciferase reporter gene assay to ensure that tp53inp1 and cdkn1a might be the direct targets of mir-106a. 25510666_2 these results implied that mir-106a directly targeted and attenuated the expression of tp53inp1, cdkn1a, and timp2 genes. 25510666_3 taken together, the upregulation of mir-106a in hcc cells promoted cell invasion partly by direct inhibition of timp2 expression. 25510666_4 these results suggested that mir-106a increased the anti-apoptotic ability of hepatic cancer cells by downregulating tp53inp1. 25510666_5 therefore, mir-106a promoted the proliferation of hepg2 cells via the regulation in g1 to s phase cell cycle progression by decreasing cdkn1a. 26256096_1 in the third subgroup of genes with transcription factor activity, two genes were found to be down-regulated by all mir-30 family members, whereas knockdown of znf174 could only been induced by introduction of mir-30c-5p and mir-30c-1-3p . 26256096_3 this indicates that the endogenous regulation of skp2 and ube2j1 may partly be regulated by the mir-30 family in cho cells. 26256096_4 finally, combined forced expression of the entire mir-30 family even resulted in a more pronounced knock-down of the skp2 protein , suggesting that skp2 might indeed be regulated by the entire mir-30 family in cho cells. 26256096_5 taken together these results support the notion that the mir-30 mirna family directly regulates skp2 in cho cells. 24520301_1 microrna-23a promotes neuroblastoma cell metastasis by targeting cdh1. 24520301_2 these findings provide evidence that mir-23a is key in promoting nb cell migration and invasion through targeting cdh1, and suggest that exogenous mir-23a may have therapeutic value in treating nb metastasis. 24520301_3 mir-23a is a candidate regulator of cdh1 in nb. 24520301_4 mir-23a directly targets cdh1 expression in nb cells. 24520301_5 therefore, it was concluded that cdh1 is a direct target of mir-23a in sk-n-sh cells, and that mir-23a regulates the expression of cdh1 at the mrna and protein levels. 20589685_1 for luciferase reporter vectors that were fused to the klf13 3'-utr fragment containing the mir- 125a binding sites, increasing doses of a mir-125a mimic reduced the luciferase activity, whereas in- creasing doses of mir-125a inhibitors increased the luciferase activity in a dose-dependent manner . 20589685_2 the results of rt-pcr showed that overexpression of mir-125a inhibited klf13 mrna expression, whereas inhibition of mir-125a expression enhanced the expression of klf13 at the mrna level . 20589685_3 taken together, our experiments indicate that mir-125a inhibits rantes expression, possibly by targeting the transcription factor klf13. taken together, these data suggest that mir-125a directly target the klf13 3'-utr. 25516599_2 therefore, we investigated whether the expression of lac13 is affected by growth conditions that impact mir408 abundance. 25516599_3 based on rt-qpcr analysis, we found that copper level and light intensity influence lac13 in the wild type in a pattern contrary to that of mir408 . 25516599_4 interestingly, in both spl7 and hy5 mutants, lac13 became less sensitive to light and copper changes and remained at relatively high levels . 25638533_1 in the inner ear hei-oc1 cell line, mir-34a overexpression inhibited sirt1,leading to an increase in p53 acetylation and apoptosis. 22373864_1 mir-301a was significantly upregulated and gax was downregulated in hcc samples compared with in the matching nontumoral tissues. 22373864_2 inhibiting mir-301a expression caused the upregulation of gax and repressed nf-kappab expression. 20807761_1 mirna-26b was identified as targeting lef-1 expression, and mir-26b represses lef-1 in pituitary and non-pituitary cell lines. 20807761_2 taken together, these data reveal a novel pathway and mechanism for the regulation of lef-1 expression by mir-26b and the subsequent regulation of pit-1 and gh expression. 20807761_3 ombined with the significant increase in lef-1 expression in the mutant mice pituitary, the mir-26 family may be an important mirna regulator of lef-1 in mousepituitary development. 20807761_4 microrna-26b directly target the lef-1 3'-utr and represses lef-1 expression. 24576478_1 we previously reported that hbx suppressed mir-205 in hepatoma cells. . 26786897_1 these data suggested that mir-509-3p could bind to the xiap 3'-utr at site 1. taken together, these data suggest that mir-509-3p directly targets xiap via its 3'-utr in 293t and ovarian cancer cells. 21802130_1 they also demonstrated that hulc rna inhibits mir-372 activity through a cerna function. 21802130_3 overall, hulc lncrna is part of a self-amplifying autoregulatory loop in which it sponges mir-372 to activate creb, and in turn upregulates its own levels. 23756231_1 microrna-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting bcl-xl and mcl-1. 22719074_1 further studies demonstrated mir-1 posttranscriptionally down-regulated the expression of calmodulin and cardiac myosin light chain kinase proteins by targeting the 3 - utrs of mylk3, calm1, and calm2 genes, leading to decreased phosphorylations of myosin light chain 2v and cardiac myosin binding protein-c . 22719074_2 targeting cmlck and cam likely underlies the detrimental effects of mir-1 on structural components of muscles related to the contractile machinery. 22719074_3 here, we found that the levels of both cmlck and cam were decreased in the mir-1 tg mice and verified mylk3 and calm1/calm2 coding for cmlck and cam, respectively, as targets for mir-1. 24504368_3 after knocking down mir-1260b, cell proliferation, invasion, migration and tcf reporter activity were decreased in pc cells. 25052764_1 anti-apoptoticprotein bcl2 was significantly upregulated by knocking down mir-34c in the hippocampus. 25052764_2 knocking down mir-34c reduces apoptosis, upregulated bcl2 and pkc-erk signaling pathway after ketamine-inducedhippocampal neurotoxicity. 25052764_3 western blotting was also used to compare bcl2 protein, phosphorylated pkc , and phosphorylated erk , between mir-34c inhibitor treated mice and control mice after ketamine-induced hippocampalneurotoxicity. 21796614_1 the mycn-induced downregulation of dkk3 results from direct upregulation of mir-17-92 components effecting both dkk3 mrna stability and translation which further contributes to the pleiotropic oncogenic effect of elevated mycn levels. 26549028_1 online database analysis tools showed that mir-193b could target mir31hg and we found an inverse correlation between mir31hg and mir-193b in pdac specimens. 26549028_2 inhibition of mir-193b expression significantly upregulated the mir31hg level, while overexpression of mir-193b suppressed mir31hg's expression and function, suggesting that mir31hg is negatively regulated by mir-193b. 19013827_1 in addition, xist and tsix rna form an rna duplexes in vivo and are processed to small rnas, which have a potential regulatory function. 19258499_3 real-time quantitative pcr revealed that mir-34b was expressed significantly less in myeloid cell lines, previously known for high creb protein levels. 19258499_4 exogenous mir-34b expression was induced, and results revealed a direct interaction with the creb 3'-untranslated region, with the consequent reduction of the creb protein levels in vitro. 19258499_5 mir-34b restored expression caused cell cycle abnormalities, reduced anchorage-independent growth, and altered creb target gene expression, suggesting its suppressor potential. 19258499_8 this epigenetic regulation should control the observed mir-34b expression levels to maintain the creb protein overexpressed. in addition, the inverse correlation between mir-34b and creb expression was found in a cohort of 78 pediatric patients at diagnosis of acute myeloid leukemia, supporting this relationship in vivo. 19258499_9 our results identify a direct mir-34b target gene, provide a possible mechanism for creb overexpression, and provide new information about myeloid transformation and therapeutic strategies. 21502955_1 mir-150 directly downregulated expression of dkc1 and akt2, reduced levels of phosphorylated akt and increased levels of tumor suppressors such as bim and bim. 26309531_1 to identify the target of mir-145 in nsclc, targetscan 6.2 was used. 26309531_2 fscn1 was predicted to be a potential target of mir-145. 26309531_3 moreover, overexpression of mir-145 significantly inhibited fscn1's expression, while inhibition of mir-145 significantly elevated fscn1's expression .4b. fscn1 was a direct target of mir-145 in nsclc cells. 21569500_2 two members of the hsa-mir-17/92 cluster, hsa-mir-17-5p and hsa-mir-20a, target the mrna of the pcaf cofactor of tat trans-activation. 26138368_1 only one predicted target of mir-31, ppp6c, was significantly downregulated at the mrna levels both after the application of imq and on the overexpression of mir-31. 26138368_3 our results demonstrate that mir-31 is capable of directly targeting a sequence within the 3- utr of the ppp6c mrna and that ppp6c is one of the key targets of mir-31 in keratinocytes. 23345523_1 in this work, we demonstrate that hendra virus makes use of a microrna designated mir-146a, an nfkb-responsive mirna upregulated by several innate immune ligands, to favor its replicationin silico analysis of mir-146a targets identified ring finger protein 11, a member of the a20 ubiquitin editing complex that negatively regulates nfkb activity, as a novel component of hendra virus replication;silencing of rnf11 promotes hendra virus replication in vitro. 19193853_2 tab2 is a direct target of mir-155 in modcs. 23702479_1 mir-145 represses camkiidelta protein expression and ca overload.we 23702479_2 confirmed camkiidelta as a direct downstream target of mir-145. 26069251_1 mir-218 directly targets zeb2, acting synergistically with the mir-200 family. 26069251_2 these data suggest that mir-218 acts to suppress emt by directly targeting zeb2 mrna on the one hand, leading to downregulation of zeb2 and therefore subsequent upregulation of e-cadherin expression, whereas on the other hand it directly targets and suppresses n-cadherin expression. 26069251_3 together, our data suggest a novel regulatory network between mir-218, mir-135b, and mir-210, the mir-200 family and several novel molecular targets for these mirnas, including zeb2, n-cadherin, two novel tumor suppressors siah1 and setd2, and the foxn3 transcription factor, which together coordinately regulate e- and n-cadherin expression, and thus the emt-associated cadherin switch. 26069251_4 our finding that mir-218 directly targets n-cadherin and leads to e-cadherin upregulation by targeting zeb2 transcription factor in synergy with the mir-200 family, together with its ability to suppress invasion and metastasis suggests a novel metastasis-suppressing role for mir-218. 22836756_1 key target of mir-21 in mediating this function were sod3 and tnfalpha. 22836756_2 in this study, we found that mir-21 affected the levels of superoxide to hydrogen peroxide in human bronchial epithelial cells by directly targeting sod3 and tnfalpha decreasing sod2 levels, and that these changes are linked to increased ir-induced cell transformation in mir-21 expressing cells. in this study, we reported for the first time that mir-21 affects ros levels through targeting sod3 and tnfalpha , which might be linked to the role of mir-21 in carcinogenesis. 20947507_1 one direct target of mir-155 repression is the mrna encoding transcription factor pu.1. 20947507_3 overexpression of mir-155 in bjab cells led to reduced levels of pu.1 and cd10 proteins and mrna . 25613903_1 these data suggest that foxm1 is a direct target of mir-149 in crc cells. 25613903_2 mir-149 significantly downregulates the expression of mmp-2, mmp-9, vegf-a and upar in crc cells by targeting foxm1. 25613903_3 mir-149 and its putative binding sequence in the 3'-utr of foxm1. 25613903_4 the mutant mir-149-binding site was generated in the complementary site for the seed region of mir-149. 8655567_1 the 93 nt micf antisense rna was showen to regulate the level of ompf in the outer membrane in response to temperature and other conditions by decreasing the level of ompf mrna,presumably through through a specifice hybridization between them.the 8655567_2 observation of the h-ns repression effect on ompf in a micf background and wildtype is compatible with the idea that h-ns affect the level of micf rna primarily and thereby may influence ompf expression.in 15944709_2 to determine whether e2f1 is a target of mir-17-5p and mir-20a, we used hela cells, which naturally express the mir-17 cluster. 2 0-omethyl antisense oligoribonucleotides, which have been shown to block mirna function24,25, were designed to inhibit mir-17-5p and mir-20a. 15944709_3 because of nucleotide similarity between mir-17-5p and mir-20a, both were inhibited by antisense oligonucleotides directed against either mirna. 15944709_4 transfection with mir-17-5p and mir-20a antisense oligonucleotides, but not scrambled oligonucleotides, resulted in an approximately fourfold increase in e2f1 protein levels without altering e2f1 mrna abundance . 15944709_6 furthermore, they suggest that the mir-17 cluster, by decreasing e2f1 expression, tightly regulates c-myc-mediated cellular proliferation. 22399519_1 ezh2 is a target of mir-25 and mir-30d. 22399519_2 we report that mir-25 and mir-30d targetthe polycomb protein enhancer of zeste 2 that has oncogenic activity and is drastically up-regulated in anaplastic thyroid carcinomas but not in the differentiated ones. 22399519_3 ectopic expression of mir-25 and mir-30d inhibited proliferation and colony formation of anaplastic thyroid carcinoma cells by inducing g2/m-phase cell-cycle arrest. 22399519_4 the down-regulation of mir-25 and mir-30d could contribute to the process of thyroid cancer progression, leading to the development of anaplastic carcinomas targeting ezh2 mrna. 20713524_1 mir-335 as a novel regulator of the tumor suppressor rb1. 20713524_2 our data identify mir-335 as a potent regulator of rb1 at the posttranscriptional level connecting the rb1 and p53 tumor suppressor pathway activities. 20713524_3 mir-335 directly target rb1 in a proximal connection to p53-dependent stress response. 20713524_5 we conclude that mir-335 efficiently controls rb1 expression by directly targeting a sequence motif in the 3'-utr of rb1 in a conserved manner. 20713524_6 we conclude that limiting rb levels by mir-335 results in a compensatory activation of the p53 pathway, aimed to protect from loss of rb-dependent cell cycle regulation and uncontrolled proliferation of human and mousecells. 26031356_1 our data suggest that androgens can directly regulate cyp2d, mir-101 and mir-128-2 levels in the brain. 21684288_4 thus, mir-9 can directly modulate pdgfr--beta mrna and protein expression in u87 cells independent of ligand activation. 22205737_2 e2f3 and ccng1 were identified as target genes of mir-203.overexpression of the targets overcame the effects of mir-203 mimics on the cell cycle, and the expression of target genes in tumor models was inhibited by mir-203. 23710316_3 bioinformatic analysis indicated that il-18 was a target of mir-197. 23710316_4 exogenous expression of mir-197 could significantly repress il-18 expression at both the mrna and protein levels in thp-1 cells. 23722270_1 co-transfection of a mimic of microrna-25 and the luciferase construct resulted in a decrease in the luciferase signal, indicating a direct binding of microrna-25 to nox4 3- utr. 23722270_2 fig. 4. demonstration of the direct binding of rat microrna-25 to human nox4 3- utr using hek293 cells. 22492316_1 virus-mediated mir-7 upregulation depended on enhanced expression of the e2f1 protein. 20623644_1 mir-149* induces apoptosis by inhibiting akt1 and e2f1 in human cancer cells. 26551255_1 fig 5 tgfb2 is a direct target of mir-599 in vsmcs. 26551255_3 cck8 analysis demonstrated that overexpression of tgfb2 promoted mir-599-induced inhibition of vsmcs proliferation . 26551255_4 moreover, ectopic expression of tgfb2 promoted the expression of type i collagen, type v collagen and proteoglycan in mir-599 overexpressing vsmcs . 26428001_1 rna electrophoresis mobility shift assays displayed direct interactions between hsa-mir-29a-3p and its cognate targets within the mrna transcripts for the abcc6, slc22a7 and aldh5a1 genes. 26428001_2 competition assays showed a sequence-specific interaction between hsa-mir-29a-3p and its cognate mrna targets in the abcc6, aldh5a1, and slc22a7 genes, since the decreases of mirna-mrna complexes occurred when excess unlabeled hsa-mir-29a-3p oligonucleotides were added to the reactions. 26428001_3 the hsa-mir-29a-3p mimic did not suppress luciferase activities for the mutated-aldh5a1 or mutated-slc22a7 constructs, indicating that hsa-mir-29a-3p targets the 3'-utrs of aldh5a1 and slc22a7 mrna in a sequence-specific manner. 26428001_4 in vitro assays proved that hsa-mir-29a-3p indeed suppressed the expression of slc22a7 and aldh5a1 in liver cells, but failed to inhibit abcc6 expression. 26549725_2 this suggests that mir-21 inhibits the expression of most tumor suppressor genes, although we did find that stat3 acting as a cancer gene can be inhibited by mir-21. 26549725_3 these data show that mir-21, which increased tumorigenic activity in functional assays, may in fact target stat3 mrna and inhibit its translation into protein. 20385359_1 here, we show that kit mutations lead to myc-dependent mir-29b repression and increased levels of the mir-29b targetsp1 in kit-driven leukemia. 20385359_2 finally, ectopic expression of myc resulted in downregulation of mir-29b and upregulation of the mir-29b targetsp1 , thereby resulting in higher levels of kit expression in kasumi-1 and mv4-11 cells . 20385359_3 sp1 is a bona fide target of mir-29b . 26055579_1 ctdspl 3'-utr is a target of mir-99a and it regulates proliferation. 26055579_2 these results show that ctdspl is a target of mir-99a. 19892940_1 c-myb was found to be a targetfor mirna-150, and rac 1 was found to be one of the target for mirna-194. 19892940_2 rac 1 protein expression was also inhibited significantly in mirna-194-transfected cells but not in ns-mirna- or mirna-150-transfected cells . 19892940_3 these data suggest that both mirna-150 and mirna-194 inhibit hsc activation and ecm expression, at least in part, via inhibiting c-myb and rac 1, respectively. 26553360_1 the luciferase activity of nacc1 and bcl6 was reduced in skov3 cells in a mir-339-5p dosedependent manner. 26553360_2 bcl6 and nacc1 were verified to be target genes of mir-339-5p in the ovarian cancer cell lines, but pappa and prl-1 were not targets. 26103003_1 these results demonstrate that mir-34a can directly target fmnl2 and e2f5 in crc cells. 26103003_2 these data make it obvious that mir-34a inhibits proliferation and invasion by targeting fmnl2 or e2f6. 18818206_3 enhanced activation of caspases 3 and 7, cleavage of their substrate parp-1, and depletion of anti-apoptotic mcl-1 contributed to the sensitivity of mir-1-expressing cells to doxorubicin. 26067553_1 to verify the mechanisms, we identified a novel mir-101 target, ral binding protein 1 . 26067553_2 thus, these results indicated that rlip76 is a novel target of mir-101. 26067553_3 we showed that rlip76 is a novel target of mir-101 in prostate cancers. 22009679_2 noticeably adcy6 3'-utr is predicted to contain one 8-mer site for mir-182 and three 8-mer sites for mir-96 . 22009679_3 as shown in supplementary figure s2d, both mir-96 and mir-182 downregulated expression of adcy6 mrna and protein, despite the fact positions of their predicted sites into the adcy6 3'-utr remain to be confirmed. 20219857_1 ischaemic preconditioning-regulated mir-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target pdcd4. 26581907_1 mir-93 binds directly to the 3'-utr of the nedd4l messenger rna , leading to a downregulation of nedd4l expression at the protein level. 26581907_2 these results demonstrated that mir-93 is able to bind to the 3'-utr of the nedd4l mrna for downregulation of gene expression. 26581907_3 these data indicate that mir-93 may regulate the expression of nedd4l by interfering with its mrna translation, but not mrna stability . in summary, these data indicate that mir-93 promotes tgf--beta-induced emt by downregulating nedd4l in lung cancer cells, and the emt markers may respond differentially in different cancer cell lines. 24859754_1 schematic representations of 3'-utrs of cytoskeletal genes cfl2, wasl, bod1, twf1, itgav, grfl1 with mir-142-3p binding sites and the corresponding mutations made to test direct interactions with mir-142-3p. 24859754_3 using luciferase reporter assays, we showed that the mrnas of wasl, cfl2, grlf1, itgav and twf1 are directly targeted by mir-142-3p figure 5h–j, figure 5—figure supplements 3 and 4. furthermore, the quantitative contributions of individual binding sites within the target 3- utr was revealed by stepwise loss of mir-142 regulation, when mir-142-3p binding sites were sequentially mutated . 24859754_4 taken together, we discovered that the expression of a compound set of actin cytoskeleton regulators is post-transcriptionally controlled by mir-142-3p. 26122050_1 therefore, the results obtained by sponge constructs suggested that mir-7a suppresses the expression of notch3 via a binding site in its 3'-utr. 26546342_3 5d, expression of acvr2b was decreased in cells exposed to mir-140-3p . 23328897_1 in our experiments, mir160 and mir393 were up-regulated after smv infection. 23328897_3 mir160, mir167 and mir390 all target arfs, directly or indirectly. 26826553_1 additionally, ets-1 is a molecular target of mir-144-3p, and silencing ets-1 expression inhibited fadu and hep2 cell invasion and migration as well as reduced hep2 xenograft tumor volume. 26826553_2 these studies suggest that mir-144-3p downregulates ets-1 protein expression. 26826553_3 these findings confirm that mir-144-3p downregulates ets-1 protein expression by targeting its 3'-utr. 26826553_4 taken together, both our in vivo and in vitro experimental results demonstrated that mir-144-3p may target ets-1 to inhibit the invasion and metastasis of lscc via suppressing emt. 25437332_1 mir-4459 could decrease the expression of its targets, cdc20b and atg13, and thus altered stemness via cell cycle and autophagy. 20127796_1 microrna-196 represses bach1 protein and hepatitis c virus gene expression in human hepatoma cells expressing hepatitis c viral proteins. 20127796_2 mir-196 directly acts on the 3'-utr of bach1 messenger rna and translationally represses the expression of this protein, and up-regulates hmox1. 26242736_1 to determine whether in vivo mir-155 levels are inversely correlated to those of ccn1, we examined ccn1 gene expression in the retina following intravitreal injection at p4 of the synmir-155 mimic in the mouse eye during the active postnatal angiogenic process. 26242736_2 syn-mir-155 reduced both ccn1 mrna and protein levels below control levels. 26242736_3 conversely, exposure of mir-155-/- mouse pups to oir increased ccn1 mrna and protein levels at p12 and markedly at p17 compared to wild-type mice. 26242736_4 mir-155 directly targets the ccn1 3'-utr leading to repressed ccn1 gene expression. 18922890_1 while this study was near its completion, we noticed an interesting report describing the ability of mir-7 to also inhibit egfr and insulin receptor substrate 1 by directly targeting the 3'-utrs of their mrnas . 18922890_5 as expected, transfection of mir-7 down-regulates the levels of egfr and irs1 proteins in hela, zr-75, and mda-231 cells . 26873752_1 this result showed that direct targeting of the 3'-utr of the ctgf mrna mediated mir-19a, -19b, and -26b-suppressed ctgf protein expression.these 26873752_2 results showed the involvement of mir-19a, -19b, and -26b in suppressing et-1- and thrombininduced ctgf protein expression and fibroblast differentiation. 26273679_1 in addition, our data suggests mir-223 regulates glut4 expression by direct binding to its 3 ' untranslated region . 26273679_2 these data suggest glut4 could be a direct target of mir-223. 26273679_3 transient cotransfection of mir-223 and luciferase expression plasmids in human differentiated adipocytes demonstrated direct binding of mir-223 to the glut4 3 ' utr site, resulting in a significant reduction in luciferase . 21159816_1 interestingly, kras and rreb1 are identified by targetscan as potential mir-143 and mir-145 targets, respectively. 21159816_3 overexpression of mir-143 reduces kras mrna and protein abundance in miapaca2 and panc-1 cells . 21159816_6 the rreb1 3- untranslated region contains one predicted mir-145-binding site, which is highly conserved in vertebrates . 21159816_7 reporter assays verified that this site, but not a mutant version, resulted in mir-145-mediated repression when placed in the 3- utr of luciferase . in addition, our studies uncovered the existence of a feed-forward loop established by the direct targeting of kras and rreb1 by mir-143 and mir-145, respectively . 20143188_1 these results suggested that pdcd4 is a target of mir-21 in hl60 and k562 cells. 20143188_2 to confirm pdcd4 as a direct target of mir-21 in hl60 and k562 cells, we construct the dual-luciferase reporter containing mir-21 recognition sequence or the mutated sequence from the 3'-utr of pdcd4 mrna immediately downstream of luciferase gene, psi-check-2-pdcd4- utr. 26898757_2 hip1r mrna levels were decreased in seminal vesicle tissue from mice bearing mir-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting hip1r is a key functional target of mir-23b/-27b. 26898757_3 together, these data demonstrate that the mir-23b/-27b cluster functions as a metastasis-suppressor by decreasing hip1r levels in pre-clinical models of prostate cancer. 26898757_4 the candidate mir-23b/-27b target, hip1r was inversely correlated with mir-23b/-27b expression in pc3-ml, alva31 and lncap cells . 26898757_5 similarly, hip1r protein levels were inversely correlated with mir-23b/-27b in pc cells . 26898757_6 figure 2. hip1r is downregulated by mir-23b/-27b in prostate cancer cells. 26898757_7 therefore, overexpression of the mir-23b/-27b target hip1r in lncap cells reproduced the phenotype observed when mir-23b/-27b levels were reduced in this cell line consistent with a potential role of hip1r downregulation by mir-23b/-27b in metastasis suppression. 26898757_8 taken together, this evidence suggests that suppression of pc invasion and migration by mir-23b/-27b may be mediated through the downregulation of hip1r. 26055341_1 a luciferase assay and western blot analysis confirmed that mir-197 directly binds to and negatively regulates tyms expression. 26055341_2 mir-197 mediates the response of colorectal cancer cells to 5-fu by regulating tyms expression. 26055341_3 to the best of our knowledge, this study demonstrated for the first time that tyms is a novel, direct target of mir-197. 25006436_1 novel research shows that mir-204, a microrna recently found to be notably downregulated through induction of parp-1 by excessive dna damage in pah, inhibits activation of stat3. 21610143_2 transfection with the mir-146a mimics resulted in a decrease in bcl-2 mrna expression and protein levels, whereas transfection with the mir-146a inhibitors induced an increase in bcl-2 expression . 21610143_3 these data suggest that mir-146a inhibits the nfκb pathway in the snk6 and yt cells and therefore might function as a tumor suppressor inhibiting cell proliferation and inducing apoptosis with the suppression of bcl-2 expression. 21693609_1 computational analysisfound a putative targetsite of mir-23a in the 3'utr of fas mrna, which wasverified by a luciferase reporter assay. 21693609_2 this finding may be attributable to the fact that this vector-based inhibitor blocked the regulatory effect of endogenous mir-23a, which would result in increased translational activity of mir-23a 3'-utr transcript. 21693609_3 here, we demonstrate that fas expression is regulated by mir-23a at posttranslational levels. 21693609_4 taken together, these results demonstrated that fas is the target of mir-23a expression for inhibition of apoptosis. 25951903_1 these results indicated that akt2 is the direct target of let-7b and let-7c in renal cancer. 25951903_2 akt2 is a functional target of let-7b and let-7c. 25951903_3 schematic representation of akt2 3'-utrs as the putative target of let-7b and let-8c. 18710431_1 sibc and ohsc rna repression of ibsc and shob expression 23016664_1 mir-125b downregulates the expression of luciferase through nestin 3'-untranslated region , and the regulation was abolished by mutations in the mir-125b bindsg site. 23016664_2 mir-125b targeted the 3'-utr of nestin and reduced the abundance of nestin at both mrna and protein levels. 23016664_3 although 3'-utr sequences of nestin are not highly conserved in mammals, the putative bindsg sites for mir-125b in nestin are also found in both human and rat . 23016664_4 the results indicated that mir-125b mimics and mir-125b inhibitors had little effect on luciferase expression with the actb 3'-utr. 23016664_5 these experiments demonstrated that mir-125b interacts directly with the bindsg site in nestin 3'-utr to regulate luciferase reporter expression. 23016664_6 taken together, these findings indicated that nestin is a direct downstream targetfor mir-125b in ns/pcs. 23016664_7 taken together, these experiments support the hypothesis that nestin is a direct target of mir-125b and that mir-125b activation in ns/pcs elicits a decrease of nestin protein. 23016664_8 taken together, our data suggested that mir-125b regulates neural stem cell proliferation, differentiation and migration through targeting nestin expression. 26272696_1 real-time pcr indicated that the over expression of h19 induced a significant increase in the vegf and icam1 transcripts, while, no modulation compared to controls was observed for the transcription of vegf-r1, vcam and ve-cadherin . 26272696_3 moreover, a rise in the number and length of tubes was found in huvecs transfected with ph19 , while facs analysis indicated an increase in the number of icam-1-expressing cells induced by h19 overexpression, thus explaining the more adhesive phenotype of huvecs. 21719785_1 mir-335 and mir-34a inhibited expression of sod2 and txnrd2 by binding to the 3'-untranslated regions of each gene, respectively. 21719785_2 to verify the correlation between mir-335 and its predicted target gene, we analyzed the expression level of sod2 in old mesangial cells by western blot. 21719785_3 the results confirmed that, in the same cells, expression of the protein was correspondingly downregulated , demonstrating that the expression level of the mir-335 target protein was inversely correlated with that of the corresponding mir-335. 21719785_5 these results suggest that mir-335 and mir-34a potentially play an important regulatory role in the aging process in mesangial cells. 21719785_6 figure 5.sod2 and txnrd2 were potential target genes of mir-335 and mir-34a, respectively. 21719785_7 to strengthen the significance of these in vitro results, the expression levels of the candidate genes sod2 and txnrd2 regulated by mir-335 and mir-34a were observed in aging rat renal tissues in vivo. 25995442_1 mir-506 sensitized cells to dna damage through directly targeting the double-strand dna damage repair gene rad51. 25995442_2 taken together, these results confirmed that mir-506 specifically targets the 3'-utr of rad51, thereby inhibiting rad51 gene expression. 25995442_3 together these results suggest that mir-506-mediated downregulation of rad51 impedes the dna damage response pathway. 25995442_4 moreover, the effect of mir-506 on cisplatin and olaparib sensitivity was fully rescued by overexpressing rad51 without its 3'-utr , suggesting that mir-506-mediated sensitivity to cisplatin and olaparib is primarily a result of rad51 expression suppression. 9770508_1 dsra acts via specific rna:rna base pairing interactions at the hns locus to antagonize h-ns translation. 9770508_3 negative regulation of hns by dsra is achieved by the rna:rna interaction blocking translation of hns rna. in contrast, results suggest that positive regulation of rpos by dsra occurs by formation of an rna structure that activates a cis-acting translational operator. 23178713_1 mirna-101 directly target sox9 in hcc tissues. 23178713_3 therefore, mir-101 may inhibited cell proliferation of hepg2 cells by targeting sox9. 23178713_4 therefore, mir-101 may suppress hcc metastasis via negatively regulating the migratory and invasive abilities of hcc cells by targeting sox9. 23178713_5 n conclusion, our data offer the first convinced evidence that mir-101 may suppress tumor progression of hcc through down-regulating sox9. 22581800_2 these data indicate that bancr is a novel brafv600e-induced lncrna that regulates melanoma cell migration in vitro in part by regulating expression of cxcl11. 22647547_1 as a potential mechanistic explanation for this observation, we demonstrate that mir30b directly targets atg12 and becn2, which are important proteins involved in autophagy. 20943204_2 8a the protein levels of pi3kp85 are significantly decreased in the db/db mice liver while that of pepck are significantly elevated . 20943204_3 these together with the fact that mir-29a levels are elevated in the liver of these animals suggest that the increased levels of mir-29a might be responsible for the decreased levels of pi3kp85 and the increased levels of pepck as observed in vivo by mechanisms described earlier. 25311243_1 microrna-30a, a member of family of micrornas that are transcriptionally suppressed by myc, directly binds to and inhibits notch1 and notch2 expression. 25311243_2 functional binding sites for mir-30a are present in the 3'-utrs of notch1 and notch2. 25311243_3 these data indicate that mir-30a directly binds to notch1 and notch2's 3'-utrs and may inhibit their expression. 26100275_1 furthermore, we characterized two akt pathway-associated molecules, akt1 and wnt16, as direct targets of mir-374b. 26100275_3 furthermore, our in vitro and in vivo studies showed that ectopic restoration of mir-374b suppressed cell proliferation and tumorigenicity and promoted cellular apoptosis by repressing wnt-16 and akt1 expression. 21969367_1 mir-138-mediated downregulation of fosl1 in squamous cell carcinoma cell lines. 21969367_3 2, the mir-138-mediated down-regulation of fosl1 was also confirmed by immunofluorescence analysis in um1 cells. 21969367_4 figure 1.mir-138 direct targeting of fosl1 mrna. 21969367_6 furthermore, significant enrichment of non-canonical mir-138 targeting sites was observed in the 3'-utr of the genes that were regulated by mir-138. 26166818_1 these results suggested that mir-134 regulate the growth of h69 cells by targeting wwox. 26044722_1 bioinformatics analysis indicated that hif1a was the possible target gene of mir-18a. 26044722_2 compared with control cells, gene expression and protein levels of hif1a dramatically decreased in cecs transfected with mir-18a mimic, indicating that overexpression of mir-18a in cecs significantly inhibited the expression of its target gene, hif1a. 24481443_1 we found that in young huvecs, mir-216a overexpression repressed becn1 and atg5 expression and the ox-ldl induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 analysis and cytofluorimetric assay. 26721309_1 these data suggest that limk1 is a likely target of mir-143 in these as-csc cells, consistent with reports of mir-143 directly targeting limk1 in non-small cell lung cancer . 21685920_1 as a consequence of mir-1 loss, expression of gja1 and cacna1c , which are target of mir-1, is increased in both dm1- and dm2-affected hearts. in addition, overexpression of mir-1 in h9c2 cardiomyoblasts reduced the level of endogenous cacna1c protein, whereas an antisense rna oligonucleotide directed against mir-1 increased the expression of endogenous cacna1c . 21685920_2 these data demonstrate a post-transcriptional upregulation of mir-1 target gja1 and cacna1c in people with myotonic dystrophy, which is consistent with a downregulation of the inhibitor, mir-1. 18308931_3 3a, a marked reduction of cd34 protein was evident in the mir-125a transfected cells compared with the scrambled oligonucleotides. 18308931_4 to further validated this interaction, we performed luciferase reporter assays, where the 3'-utr of the cd34 gene predicted to interact with mir-125a, was cloned in to the luciferase reporter assay and cotransfected with mir-125a oligonucleotide or scrambled oligonucleotides into meg-01 cell lines using lipofectamine. 24440503_1 a feedforward regulatory loop between hur and the long noncoding rna linc-md1 controls early phases of myogenesis 26566162_1 cdc42 was the direct target gene of mir-137 and proteins of cdc42, caspase-3, and caspase-9 were all regulated by mir-137 down-regulation in cardiomyocyte apoptosis. 26566162_2 the results showed that mir-137 significantly reduced the luciferase activity in hek293t cells while cdc42-wt was co-transfected, as compared to the cells co-transfected with cdc42-mu , confirming that cdc42 was a direct target of mir-137. in this work, we first demonstrated, by dual-luciferase reporter assay, that cdc42 was the direct target of mir-137. 23185331_1 additionally, we show downregulation of known mir-155 and/or kshv-mir-k12-11 targets in mirna-expressing bm cells in vivo and confirm jarid2 as a novel target of kshv-mir-k12-11. 23185331_2 collectively, the above data confirm jarid2 as a shared target of hsa-mir-155 and kshv-mir-k12-11 which, consistent with its downregulation in hsa-mir-155 and kshv-mir-k12-11 expressing bm cells, may be one of the factors contributing to the observed phenotypes in vivo. 23185331_3 additionally, we validate jarid2 as a novel target of kshv-mir-k12, and for the first time demonstrate that hsa-mir-155 as well as kshv-mir-k12-11can efficiently suppresses protein expression from an authentic jarid2-encoding transcript. 24169356_1 mir-125b acts as an oncogene in glioblastoma cells and inhibits cell apoptosis through p53 and p38mapk-independent pathways. 24169356_2 moreover, p38mapk is also regulated by mir-125b and downregulation of mir-125b activates the p38mapk-induced mitochondria apoptotic pathway. 22683624_1 we show that satb1 and cdk6 3'-utrs are two mir-191 direct target involved in this pathway. 22683624_3 overexpression of mir-191 by transfection in proliferating hekn led to a significant decrease in satb1 and cdk6 protein levels , thus demonstrating that mir-191 is able to repress the selected target endogenously expressed in keratinocytes. 22716646_2 further studies confirmed that mir-29b regulated the expression of mcl1 , mmp2 , vegfa and itgb1 genes by directly binding to their 3'-utrs . 26742429_1 we also identified notch1 as a direct target of mir-935. 26742429_2 we conclude that mir-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting notch1, suggesting potential applications of the mir-935-notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma. 26742429_3 it was found that mir-935 may play as a tumor suppressor gene by targeting notch1 3 ' utr in gastric cancer, which is more obvious in gsrcc. 26742429_4 these results indicated that notch1 is a target gene of mir-935, and the position of 1593e1599 in the 3 ' utr of notch1 is the mir-935 binding site. 26742429_5 this result implies that mir-935 influences notch1 mrna by binding its 3 ' utr. at the same time, we demonstrated by dual luciferase report system that mir-935 inhibits translation of notch1 by binding to its 3 ' utr, and decreases its mrna and protein expression 23784029_1 mir-21 binds to the 3' utr of smad7 mrna and inhibits its translation, rather than causing its degradation. 23784029_2 mir-21 regulates the smad 7 protein level through translation inhibition. in this study, we demonstrate that mir-21 lowers the expression of smad7 through translation inhibition rather than mrna decay, and that tgf-b activates the regulatory smad 2 and 3 proteins by reducing the association of smad2/3 with smad7. 18814950_1 mir150 affects a c-myb 3'-utr reporter gene. 18814950_2 using a reporter gene containing the c-myb 3'utr region, including its four mir150 binding sites, we found that expression of mir150 reduced luciferase expression to 50% of baseline at 24 hours and to 25% at 48 hours in ut7/tpo cells. 18814950_3 quantitative polymerase chain reaction and western blotting also revealed that mir-150 reduced endogenous c-myb mrna and protein to 50% in ut7/tpo cells, and to 65% in mature megakaryocytes. 21199804_1 to explore the mechanism of growth inhibition induced by mir-26a, we investigated whether mir-26a could regulate ezh2 expression in npc cells. 21199804_3 taken together, all these results strongly suggested that ezh2 was a direct target of mir-26a in npc cells. 12702581_1 we have examined the expression of igf2 and igf2-as in normal tissue, breast and ovarian tumors, and 25 informative, well-characterized wilms' tumors and determined the relationship between igf2 and igf2-as imprinting. 12702581_2 igf2-as was expressed at levels comparable with igf2 sense expression derived from promoters p1 and p2 in normal tissue and in breast, ovarian, and wilms- tumor tissues. in wilms' tumors that demonstrate maintenance of imprinting of igf2, igf2-as was imprinted. 19250907_1 wrap53 regulates p53 via wrap53/p53 rna interaction. 19250907_2 the fact that wrap53 specifically regulates the mature form of p53 rna further supports the notion that wrap53 regulates p53 at the posttranscriptional level. 19250907_3 these experiments demonstrate that p53 mrna is regulated by wrap53 through sequences in exon 1 of p53 and that the length of p53 exon 1 is important for this effect. 19250907_4 thus, the antisense arrangement of p53 and wrap53 is conserved between human and mouse supporting the notion that it has a significant function and that wrap53 regulates p53 through the antisense overlap. 19250907_5 this also suggests that p53 and wrap53 rna interact in the cytoplasm. 19250907_6 these results demonstrate that wrap53 expression and interaction with p53 mrna is necessary for proper induction of p53 upon dna damage by maintaining sufficient levels of p53 rna. 25955435_1 bdnf is a novel target gene of the hsa-mir- 183/96/184 cluster 26631045_1 furthermore, kras was identified as a target of mir-613. 26631045_2 reintroducing kras rescued the inhibitory effects exerted by mir-613 on ovarian cancer cell proliferation and invasion. 26631045_3 taken together, our findings suggest that mir-613 functions as a candidate tumor suppressor mirna in ovarian cancer by directly targeting kras. 23835407_1 a luciferase assay demonstrated that mir-375 down-regulated p53 expression through an interaction with the 3' utr region of p53.flow cytometry analyses showed that mir-375 abrogated the cell cycle arrest and apoptosis after dna damage. 20458444_1 mir-20a target directly at the app 3' utr. 20458444_2 from these results, we concluded that mir-20a could negatively regulate app expression through directly binding to the special sequence of app mrna 3' utr. 20458444_3 we found that when mir-20a was inhibited, the mrna level of app was increased . 20458444_4 furthermore, the data of western blot assay also showed a reverse correlation of mir-20a and app protein level . 20458444_6 thus, we could conclude that mir-20a facilitates proliferation and invasion by down-regulating app gene in ovarian carcinoma. 23100393_2 moreover, we show that mir-29b target dnmt3a and dnmt3b mrnas and reduces global dna methylation in mm cells. 23100393_3 mir-29b target dnmt3a and dnmt3b and reduces global dna methylation levels in mm cells. 23100393_4 consistently, mir-29b transfection reduced dnmt3a and dnmt3b mrna and protein levels , as assessed by q-rt-pcr and western blotting analysis. 23100393_5 of note, mir-29b inhibition indeed led to up-regulation of both dnmt3a and dnmt3b protein levels, as assessed by western blotting analysis . 23100393_6 we observed significant tumor growth inhibition in mice treated with mir-29b mimics, together with 2-fold increase of mir-29b levels and down-regulation of both dnmt3a and dnmt3b mrna levels as assessed by qrt-pcr analysis of the excised tumors. 23100393_7 we here demonstrate that synthetic mir-29b mimics specifically bindthe 3'utr of dnmt3a and dnmt3b, resulting in downregulation of both dnmts at mrna and protein level; conversely, mir-29b inhibition by antagomirs led to increased dnmts expression levels. 25776481_1 fig. 4. mir-377 directly targeted e26 transformation specific-1 . 25776481_2 these finding indicate that mir-377 inhibits the expression of ets1 by binding to complementary sequences in the 3' utr of ets1. 25776481_3 taken together, these results suggest that mir-377 can inhibit ccrcc development by downregulating ets1. 26553749_1 together our data suggest that mir-212, and to a lesser extent mir-22, may play a pivotal role in regulating the endogenous levels of hnrnph1 and all ar transcripts in prostate tumor cells. 26553749_2 taken together, the results implicate that down-regulation of mir22 and/or mir-212 triggers endogenous accumulation of hnrnph1 transcripts, which in turn upregulates transcription of ar-fl and ar-v7, potentially through transcriptional regulation and/or slicing activity in prostate tumor cells. 25016614_1 this effect of mir-210 was associated with functional downregulation of its validated targets, ephrin a3 and ptp1, but not flash/casp8ap2. 25381221_2 the target prediction programs predicted that the 3'-utr of trim33 mrna contained complementary sequence for the seed region of mir-629. 25381221_3 these results indicated that trim33 is a target of mir-629 in the ccrcc cells. 26330104_1 seed sequence base-pairing between mir-34a and 3'utrs of pparalpha as predicted by targetscan. in 293t cells using luciferase reporter assays. 26330104_2 figure 3a shows the predicted mir-34a-binding sites in 3'utr of pparalpha. 26330104_3 these data suggested that mir-34a downregulated the expression of pparalpha by targeting the pparalpha-3' utr 5080 site to facilitate translational repression or mrna degradation. 26259252_3 western blot analysis showed that enhanced expression of mir-99b-5p triggered a silencing effect on mtor protein expression and its phosphorylation. 26259252_4 after transfection with the mir-99b-5p inhibitor in ht-29 cells, expression of mtor and its phosphorylation products were increased. 26259252_5 mir-99b-5p could decrease the relative luciferase activity of the mtor 3- utr construct whereas, in the counterpart with the mutated site, the luciferase activity was not significantly changed , indicating that mir-99b-5p down-regulates mtor expression by directly targeting its 3- utr . 25760076_1 according to the data from three public algorithms including targetscan, pictar, and miranda, twist1 could be a potential target of mir-106a. 25760076_2 western blotting analysis also showed that increased level of twist1 was observed in hcc cells after mir-106 inhibitor treatment .3b. to further verify the twist1 as a target of mir-106a, we performed reporter assays in hcc cells with the luciferase gene driven by either wild-type or mutated twist1 3'-utr sequences .3c. altogether, these findings support that mir-106a binds to twist1 and that twist1 is a downstream target of mir-106a. 26213997_2 to investigate whether expression of genes targeted by mir-206 differed in preeclampsia, the expression of vascular endothelial growth factor , insulin-like growth factor 1 and neurogenic locus notch homolog 3 was also measured in the same placental tissue. 22159222_1 mir-34a down-regulated expression of multiple oncogenes including c-myc by targeting its 3' untranslated region, which was revealed by luciferase reporter assays. 22159222_2 since we found that mir-34a down-regulated the expression of c-myc by targeting its 3'-utr , we examined whether the down-regulation of c-myc by mir-34a results in reduction of rhoa expression through decreasing the assembly of the c-myc-揝kp2-揗iz1 complex. 22159222_3 these results suggested that mir-34a reduced the recruitment of c-myc-揝kp2-揗iz1 complex to the rhoa promoter reducing rhoa expression. 22159222_4 these results suggest that mir-34a inhibits invasion at least partially via rhoa reduction by targeting c-myc. 25033200_1 modeling studies suggest that mir-16 binds to and decreases expression of vps4a. 25033200_2 the novel target of mir-16, vps4a that we identified and validated in vitro, increases in peripheral blood of end stage hf patients and decreases one week following lvad therapy. 25033200_3 taken together, these experiments suggest that mir-16 interacts with vps4a and that circulating expression of mir-16 is down-regulated with hf while expression of its target, vps4a, is increased. 24269020_1 mir-743b-5p were observed to markedly repress the reporter activity of dj-1 mrna . 26870229_1 these findings indicate that vegf-c is a direct target of mir-101 in hepg2 cells. 26870229_2 therefore, the protein expression of vegf-c was downregulated by mir-101 in hepg2 hcc cells. 19676043_1 to investigate into the potential function of mir-153 in glioblastmas, we transfected a glioblastoma cell line dbtrg-05mg with synthetic mir-153 oligos and observed decreased cell proliferation and increased apoptosis. 19676043_3 indeed, western blot analysis indicated that mir-153 down-regulated both bcl-2 and mcl-1 at the protein levels. 19676043_4 single strand mir-153 inhibitor, which forms complementary base-pair with endogenous mir-153, efficiently blocked the apoptosis and target protein degradation induced by over-expression of mir-153. 19676043_5 by luciferase reporter assays, we further showed that mir-153 inhibited bcl-2 and mcl-1 expressions by directly targeting the 3'utr regions of their respective mrnas. 19676043_6 taken together, these evidences establish that mir-153 is a regulator of apoptosis and suggest that mir-153 may be a potential therapeutic molecule for glioblastoma. 23327642_1 luciferase activity of the wt tnp2 3'-utr reporter gene was significantly inhibited by wt mir-122 , while the luciferase activity of the mutated tnp2 3'-utr reporter gene was not inhibited by wt mir-122, indicating that mir-122 targets the tnp2 3'-utr.western 23327642_2 blotting analysis showed that tnp2 was expressed at low levels in mir-122-transfected ips cells during induction, but not in mir-122-mut-transfected cells . 23327642_3 after induction in vitro, the expression of tnp2 steadily increased over time in mir-122-mut-transfected ips cells. 26546436_1 further studies revealed that the pkm2 was a regulative target of mir-122 in gbc cell. 26546436_2 consequently, exogenous mir-122 was demonstrated to suppress cell proliferation, migration, and invasion; induce apoptosis and cell cycle arrest; and inhibit epithelial-mesenchymal transformation by targeting pkm2 in gbc cell lines, suggesting that increasing mir-122 levels in gbc may be a promising strategy for gbc treatment. 26546436_3 we demonstrated that pkm2 can be post-transcriptionally regulated by mir-122 in vitro, leading to the downregulation of pkm2 protein, effectively reducing cell growth in gallbladder cancer cell lines. 26261507_1 these results support the bioinformatics prediction indicating the 3'-utr of pac1 mrna as a target for mir-34c-3p. 26261507_2 taken together, these data demonstrate that pac1 is a direct target of mir-34c-3p and further suggest that mir-34c-3p may exert its apoptosis promoting effect through inhibition of pac1 expression. 26261507_3 when blocking the expression of mir-34c-3p with mir-34c-3p inhibitor, we get increased luciferase intensity in 293t cells . 23125283_1 these results demonstrate that mir-205 suppresses the expression of lrrk2 protein through the direct targeting the 3'-utr of lrrk2. 23125283_2 together, these analyses support the hypothesis that the downregulation of mir-205 expression contributes, at least in part, to the elevation of lrrk2 protein expression in the brains of patients with sporadic pd. 23125283_4 together, these results demonstrate that endogenous mir-205 is a suppressor of lrrk2 protein expression in the cells. 23125283_5 taken together, these results demonstrate that overexpression of mir-205 rescues the mutant lrrk2-induced neurite outgrowth defects through the suppression of lrrk2 protein expression. 23125283_6 together, these data support an inverse correlation between the expression of lrrk2 protein and mir-205 in the mousemidbrain in the aging process. 23125283_7 it suggests that the expression of lrrk2 protein can be dynamically regulated by mir-205 in the midbrain during the normal aging. 21828058_1 mir-214 regulates ezh2 protein accumulation in breast cancer cells by directly targeting ezh2 3'utr. 21828058_2 mir-214 expression was inversely correlated with ezh2 mrna. in addition, mir-214 expression did not affect the levels of bmi1, a component of the prc1 complex, indicating targeting specificity of mir-214 for ezh2 . 21828058_3 fig. 2.mir-214 overexpression reduces ezh2 levels by targeting the 3- utr of ezh2 in breast cancer cell lines. 21828058_4 collectively, these results indicate that mir-214 regulates ezh2 protein accumulation in breast cancer cells by directly targeting ezh2 3- utr. 26112171_1 the results reported here demonstrate that fos is a direct target of mir-146a activity and that downregulation of the fos-揂p-1 pathway by mir-146a has the capacity to inhibit mmp-9 activity. 25205654_1 we showed that in mdr colorectal cancer cells, mir200c targeted the 3- untranslated region of the jnk2 gene. in summary, we found that mir200c negatively regulated the expression of jnk2 gene and increased the sensitivity of mdr colorectal cancer cells to chemotherapeutic drugs, via inhibiting the jnk2/p-jnk/p-c-jun/abcb1 signaling. 25205654_2 here, we report for the first time that mir200c was significantly downregulated in human colorectal cancer mdr cells and in clinical recurrent tumor samples, mir200c targeted jnk2 gene 3'-utr directly to affect phosphorylated jnk-mediated signaling, and overexpression of mir200c downregulated the levels of abcb1/p-gp via the jnk signaling pathway, resulting in increased sensitivity to chemotherapeutic drugs and decreased metastasis in vitro and in vivo. 25205654_3 taken together, these data supported our hypothesis that the expression of jnk2 was, at least in part, regulated by mir200c in mdr colorectal cancer cells. 25205654_4 our data supported this hypothesis by demonstrating that jnk2 is a direct target gene of mir200c. 25894378_1 to determine how mir-125b promotes cancer cell apoptosis,we used public database targetscan and found mcl-1 maybe the putative target of mir-125b. 25894378_3 moreover, decreased mcl-1 expression level was observed by qpcr and western blot analysis in mcf-7/dr cells transfected with mir-125b compared with control cells. 25894378_4 mir-125b was almost unaffected , indicating that mir-125b may suppress the expression of mcl-1 through the binding sequence at its 3'-utr. 25894378_5 these results suggest that the expression of mcl-1 was negatively regulated by mir-125b, and mcl-1 gene is the target of mir-125b to reverse the dox resistance in breast cancer cells. 24438167_3 further studies demonstrated that mir-302b post-transcriptionally down-regulated the expression of erbb4 in vitro. 26381867_1 this finding is consistent with mir-19a binding to the 3- utr of grin2a mrna as a putative target. 26381867_2 validation of the grin2a mrna 3'-utr as a mir-19a target. 26895377_1 together, these results strongly suggest that mir-30e upregulates p21 expression not at the translational level by direct binding to its 3'-utr, but rather indirectly most likely via repression of factors regulating p21 transcription. in summary, the identification of caspase-3 and p21 as direct and indirect mir-30e targets that are differentially regulated in hct116 and rko cells, explains our observation that only the former, but not the latter cells, can be rescued from dna damage-induced cell death and driven into senescence. 26827826_2 as shown in figure 4a, mir-26b evidently decreased pnf-kappab s536 and mmp-9, vegf expression at the protein level in 95d. 21264258_1 a binding site for mir-26b was identified in the 3'utr of epha2. 21264258_2 the putative mirna response elements of mir-26b were also found in the 3'-utrs of epha2 in other vertebrates when compared across distant species . 21264258_3 these results suggest that mir-26b is likely to be an important regulator of epha2. 21264258_4 these data indicate that the predicted mre is critical for the direct and specific binding of mir-26b to epha2 mrna. 21264258_5 these results indicate that mir-26b is a regulator of eph2a in glioma cells, and that the mirna can down-regulate the expression of epha2 at the protein level. 21264258_6 these results provide solid evidence that mir-26b suppresses glioma cell proliferation, migration and invasion activity in a manner dependent on epha2 expression level. 21264258_7 these results suggested that epha2 plays a key role in the vm formation, and mir-26b affects the vm formation by down-regulation of epha2 expression in glioma cells. 26725326_1 we found that mir-630, which is upregulated under hypoxic conditions, targets and downregulates dicer expression. in the current report, we show a novel mechanism by which mir-630, which is upregulated under hypoxic conditions, regulates dicer expression by directly targeting the dicer 3- -untranslated region . 26725326_2 we provide evidence that mir-630, which is transcriptionally upregulated under hypoxic conditions, targets and decreases dicer expression. 22020746_1 taken together, our results provide important evidence that mir-146a can directly target smad4, and suggestthat mir-146a may play a role in the development of gastric cancer by modulating cell proliferation and apoptosis. 22020746_2 these results suggest that smad4 is a direct target of mir-146a in gastric cancer cells, and mir-146a may negatively regulate the expression of smad4. 22020746_3 above results suggest that mir-146a expression is inversely correlated with smad4 expression in gastric cancer. 22020746_4 figure 4.identification of smad4 as a potential target of mir-146a in gastric cancer. 22020746_5 figure 5.the mir-146a expression is inversely correlated with the expression of smad4 in gastric cancer. 24576947_1 icam-1 is a direct target of hdl-transferred mir-223 and this is the first example of an extracellular mirna regulating gene expression in cells where it is not transcribed. 24576947_2 these findings strongly suggest that hdl repression of icam-1 is mediated, at least in part by mir-223 directly targeting the 3- utr of icam-1 in hcaec. 24576947_3 here we demonstrate that mir-223 is transferred from native hdl to endothelial cells, mir-223 is not transcribed in hcaec and hdl do not induce mir-223 transcription in endothelial cells, and mir-223 directly targets icam-1 in hcaec. 23298779_1 mir-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as e2f3, bcl-2, c-myc and cyclin d1. 24155920_1 functional studies showed that mir-21 over-expression in gics induced comparable cell differentiation features and targeted spry1 mrna, which encodes for a negative regulator of neural stem-cell differentiation. 24155920_2 these data show that mir-21 targets spry1 by direct 3'-utr binding, suggesting that mir-21 is probably involved in the decrease of spry1 protein expression observed during gic differentiation. 24155920_3 furthermore, in this study we demonstrate that spry1 is a direct target of mir-21 in gics, and it has been reported that spry1 inhibition promotes neural differentiation in mouse embryonic stem cells . 20624637_1 the deregulation of mir-27a may be involved in the development of drug resistance, regulating the expression of mdr1/p-gp, at least in part, by targeting hipk2 in ovarian cancer cells. 20624637_2 hipk2 may be a target of repression by mir-27a. 21967153_1 these results led us to suggest that these three mirnas, mir-470, mir-669b, and mir-681, are each functionally capable of repressing the expression of igf1r as well as akt, inducing lower foxo3a phosphorylation status, thus dampening the igf1 pathway by posttranscriptional control in the brain of long-lived mouse mutants. 21967153_2 taken together, our results suggest that mir-470, mir-669b, and mir-681 are all functionally able to suppress igf1r and akt, two upstream genes controlling foxo3a phosphorylation status. 26236156_2 to investigate the possible mechanism of down-regulation of mirna-21 by mir-21 aso in the proliferation and migration of colon carcinoma, we further detected the expression of pten in human colon carcinoma hct116 cells. 26236156_4 4a, b, the expression of pten protein was significantly elevated in p-mir-21-aso transfected group compared with that in p-cont transfected group . 26236156_5 to further verify the expression of pten, we also analyzed the expression of pten protein in hct116 cells using facs analysis and similar result was obtained. 21378409_2 a search for the targets of mir-1 revealed that transgelin 2 was directly regulated by mir-1. 18692484_1 thus, bcl-w is a direct target of mir-122 that functions as an endogenous apoptosis regulator in these hcc-derived cell lines. 18692484_2 this suggests that mir-122 specifically target to bcl-w in these cells. 18692484_6 these data confirm that bcl-w down-regulation by mir-122 triggers apoptosis and that the level of mir-122 expression is important for this mechanism. 26882562_1 thus, we demonstrated that nuak1 is a novel target gene for mir-203 in hnscc cells. 26147104_1 furthermore, mirna functional analysis and luciferase reporter assay demonstrated that mir-9 effectively regulated myocardin expression by directly binding to its 3'-untranslated region. 26147104_2 both the knockdown of mir-9 and overexpression of myocardin effectively attenuated the hps rat serum-induced phenotype switch and proliferation of pasmcs. 26147104_3 taken together, the findings of our present study demonstrate that mir-9 is required in hps rat serum-induced phenotypic modulation and proliferation of pasmcs for targeting of myocardin and that mir-9 may serve as a potential therapeutic target in hps. 24954504_2 we determined that all three targets are directly regulated by mir-124, as luciferase levels decreased upon mir-124 expression in cells expressing the wild type 3'-utr regions, but not in cells expressing 3'-utr regions with mutated mir-124 seed sequences . 24954504_3 tead1, mapk14/p38alpha, and serp1 are mir-124 direct targets. 19538740_1 of interest, we found that mir-503 not only suppressed the luciferase activity, but also suppressed the endogenous ccnd1 both at protein and mrna levels. 19538740_2 western blot analysis indicated that only mir-503 was able to suppress ccnd1 protein by over 40% in umscc10b cells in addition to its ability to suppress the luciferase activity . 19538740_3 moreover, we examined the ccnd1 mrna by real time pcr and found that only mir-503 significantly reduced ccnd1 mrna . 21704009_1 tgf--beta receptor-1 was found to be a target of mir-200b/c and was down-regulated after overexpression of mir-200c. 21704009_2 tgf-beta-r1 was also found to be up-regulated at the gene expression level, which correlates with members of the mir-200 family being down-regulated. 21704009_3 targetanalysis of mir-200b and mir-200c found that tgf-betar1 was a targetfor these mirnas with six seed matches in the rat this study shows that tgf-betar1 is a target of the mir-200 family and suggests the mir-200 family are important regulators of tgf--beta signaling, being able to influence multiple parts of the signaling pathway. 25907560_1 targetscan analysis predicted cox-2 as a target of mir-26a and mir-26b. 25907560_3 mir-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting cox-2. 25907560_4 mir-26a/-26b negatively regulated the expression of mip-2. 25907560_6 these results suggest that mir-26 and mir-26b target the expression of cox-2 to regulate allergic inflammation. 25907560_7 these results suggest that mir-26 inhibitors target cox-2 to regulate in vitro allergic inflammation. 25907560_8 these results suggest that mir-26a inhibitor and mir-26b inhibitor induce features of in vivo allergic inflammation by targeting cox-2. 26191195_1 we found that jak2 contained theoretical mir-204 binding sites in its 3- utr . 26191195_3 additionally, we found overexpression of mir-204 significantly inhibited both the mrna and protein expression of jak2, which was abolished by co-transfection of mir-204 inhibitor. 26800049_1 pten has previously been identified by a par-clip method as a potential target of mir-bhrf1-3. 26800049_2 we wished to confirm that this effect was due to the absence of mir-bhrf1-3 and assessed expression of pten in cells infected with the δ3 or the 3sm virus. 26800049_4 cotransfection of either of these constructs together with a mir-bhrf1-3 expression plasmid revealed a modest but statistically significant decrease in relative luciferase activity in the wild type pten 3'-utr fusion that was not visible in the seed-match mutant control . 26153983_1 the electroporation of anti-mir-221, anti-mir-222 or both was accompanied by an increase in p57kip2 protein level, and p27kip1 increased only when mir-221 was inhibited. 26153983_3 nevertheless taken together, the data established to our satisfaction that p57kip2 and p27kip1 are targets of the mir-221/mir-222 cluster in ebv-transformed human b cells. 26153983_4 these results suggest that mir-221 and mir-222 not only block translation, but might also enhance the degradation of p57kip2 mrna both mechanisms of action have been described. 26352220_2 western blot analysis indicated that the overexpression of mir-128 significantly downregulated irs1 expression and its downstream akt signaling in crc cells. 26352220_3 figure 5. mir-128 targets the 3'utr of irs-1 and downregulates its expression. 26352220_4 taken together, these data suggested that mir-128-induced irs1 underexpression potentially reduced downstream akt signaling. 26531836_2 furthermore,mir-19a and mir-19b targeted tp53inp1 mrna. 23430586_2 and regulatory function of mirna-182 in triple-negative breast cancer cells through its targeting of profilin 1. 26336578_1 regarding the question of whether slco1b1 could be directly regulated by the mature mir-511, luciferase assays were performed using chang liver cells. 26336578_2 dual-luciferase assays were performed by constructing slco1b1 3'-utr vectors to test the effect of mir-511. 26336578_3 mir-511 mimics/inhibitors and slco1b1 3'-utr vectors were co-transfected. 26336578_5 by transfecting mir-511 mimics with different concentrations , the slco1b1 mrna and protein levels significantly decreased compared with the control . 26336578_6 however, by transfecting mir-511 inhibitors at a concentration of 200 nm into steatosis cells with rising levels of mature mir-511, the levels of slco1b1 mrna and protein did not change. 22343732_1 the enforced expression of mir-17, a major member from this family, reduced the expression of the tumor suppressor genes e2f5, tp53inp1, trim8 and zbtb4, and protected cells from serum-free-induced apoptosis. 20495188_1 using a luciferase reporter assay and overexpression of mir-146a, we confirmed that mir-146a target the erbb4 3'utr. 20495188_2 these results suggested that up-regulation of endogenous mir-146a after dox treatment can affect myocardial erbb4 expression post-transcriptionally. therefore, we speculated that dox-induced apoptosis resulted from the down-regulation of erbb4 by mir-146a. 26183619_1 pdgf not only increased mir-21 expression but also decreased phosphatase and tensin homolog ,a well-established target gene of mir-21 in vascular remodeling.7 simultaneous anti-21 treatment diminished pdgf-mediated pten suppression, confirming the intermediary and crucial role of mir-21 . 21897745_1 a luciferase reporter assay and inhibition of endogenous rax wereperformed to confirm whether rax is a direct target of mir-29b as predicted bythe in silico analysis.results: 21897745_2 we found that mir-29b and rax are localized in the retinal ganglioncells and the cells of the inner nuclear layer of the retinas fromnormal and diabetic rats.//our 21897745_3 results suggest that rax expression may be indirectly regulated by mir-29b 22017809_1 moreover, mir-184 downregulated nuclear receptor corepressor 2 by targeting its 3' untranslated region through inhibiting ncor2 protein translation.mir-184 22017809_3 based upon the above-mentioned reasons, we focused our efforts on mir-184 and ncor2 mrna interactions. 22017809_4 taken together, we conclude that ncor2 is the targetgene of mir-184. 22017809_5 these results indicate that mir-184 could downregulate ncor2 through inhibiting translation in vitro. 19608627_2 4a, transient overexpression of mir-92 in 32d cells resulted in a decrease of the np63 protein level compared with that observed in cells transfected with the scrambled oligonucleotide or in nontransfected cells. 19608627_3 taken together, our results demonstrate that mir-92 modulates the expression of the p63 alpha and -beta isoforms and indicate that it inhibits their mrna translation. 19608627_4 to validate p63 as a target of mir-92, we set up transfection experiments in these cells. 26558781_1 here,we report that the stemness regulator sox2 is a new, clinically important target of microrna-21 in gbm, with implications for prognosis. 26558781_2 together, these results indicated that mir-21 interacts with the single, specific binding site present on the sox2 3'-utr. 26558781_3 sox2, which is required to maintain stem cell characteristics, or -渟temness,- in neural cells , was identified as the top predicted target and one of the top inversely correlated genes , suggesting that mir-21 suppresses sox2 and that the two have an inverse relationship in gbm 21829658_1 there are two different binding sites of mir-144 at the 3'-utr of irs1. the bindings sites of mir-144 at the 3'-utr of irs1 and the different constructs designed to show that mir-144 directly targets irs1. 21829658_2 to demonstrate that irs1 is a direct target of mir-144, we constructed independent reporter vectors that contained the different combinations of binding sites of mir-144 at the 3'-utr of irs1. 23298640_1 these data suggest that specific members of mir-34 and mir-449 family modulate hnf-4alpha expression by binding to the specific sites in the 3'-utr of its mrna, and that multiple but the specific mirna targetsites in the 3'-utr are involved in the regulation of hnf-4alpha expression. 23298640_2 because these hnf-4alpha targetgenes have been known to play an important role in the acute phase response, mir-34a, mir-34c-5p and mir-449a may be involved in hepatic acute phase response via regulation of hnf-4alpha expression. 23298640_3 our data from fig. 5 suggest that mir-34a, mir-34c-5p and mir-449a specifically suppress hnf-4alpha binding activity. 22244746_2 for example, our data showed that robo1, a putative target gene of mir-152, was expressed 29 times greater in mns vs nbcs, and 1.8 times greater in mns vs npcs , whereas mir-152 was expressed -44.2 times less in mns vs nbcs, and -5.7 times less in mns vs npcs . 17205120_1 mir-15b and mir-16 down-regulated upar, whereas construct ii up-regulated its expression. 17205120_2 it is probable that the fragment of vegf 3'-utr in construct ii competed with upar for endogenous mir-15b and mir-16 . 17205120_3 the expression of cox2 was down-regulated by mir-15b, mir-16, and mir-20b, and c-met was down-regulated by all three of these mirnas plus mir-20a. 26221053_1 to identify the relationship between mir-194 and nf-kb in hcc cells, we first investigated the endogenous abundance of mir-194 in five human hcc cell lines and one normal human liver tissue. 26221053_2 this result indicates that mir-194 might be an impediment to the activation of nf-kb in hcc cell lines. 26221053_3 these results suggested that mir-194 inhibits downstream nf-kb signaling, phosphorylated p65, without targeting upstream regulators. 26590946_1 further data also showed that mouse bach2 mrna was a novel target of mir-30b. in addition, mouse bach2 mrna, a novel target of mir-30b, was also confirmed. 21809363_1 in addition, mir-637 overexpression negatively regulated stat3 phosphorylation by suppressing autocrine leukemia inhibitory factor expression and exogenous lif-triggered stat3 activation and rescued cell growth in these cells. 23577194_1 hcv core protein enhances the expression of microrna-345 which then down-regulates p21 expression. 23577194_2 it is the first time that hcv core protein has ever been shown to suppress p21 gene expression through mir-345 targeting.hcv 23577194_3 core-induced microrna-345 suppressed p21 gene expression through targeting its 3'-untranslated region in human hepatoma cells. 26302069_2 we here showed that mir-200c is downregulated in mft by promoter methylation, which is functionally linked to jagged1 upregulation. 26302069_3 we propose that restoring the expression levels of mir-200c and other micrornas targeting notch1 could represent a potential and future therapeutic target in this subtype of lymphomas. 23723074_1 mir-133a inhibits rffl by direct interaction with its 3'-utr rffl contains an evolutionarily conserved binding site for mir-133a and was also reported to attenuate p53 signaling transduction . 23723074_2 indicting the direct regulation of mir-133a in the 3'-utr of rffl mrna. 26348138_1 in this study, we identified ibp2 as one of the targets for mir-278-3p by using luciferase reporter assay. 26348138_2 considering the potential roles of ibp2 and bmo-mirnas in bmcpv infection, based on bioinformatics tools and luciferase reporter assay, we identified ibp2 as a target gene for mir-278-3p. 26348138_3 it suggested that ibp2 is one of the target genes for mir-278-3p. 26348138_4 the results of luciferase reporter assay confirmed the positive interaction of mir-278-3p with ibp2 . 26290438_2 overexpression of mir-186 significantly inhibited the luciferase activity of the wt nsbp1 3'-utr reporter gene but not the mut reporter gene . 26290438_3 these results demonstrated that nsbp1 is a direct target of mir-186 in bc cells . 26223867_1 mir-106b directly targets dlc-1 in crc cells. 26223867_2 thus, these findings show that dlc1 is a functional target of mir-106b. 22373578_1 igf1r is a direct target of mir-493 and partially mediates the inhibition of liver metastasis by mir-493. 22373578_2 functional luciferase assays indicated that the 3- utr of igf1r was repressed by mir-493. 23950948_1 we further identified cdk6 as a putative target of mir-105 which is likely a main contributor to the inhibition of tumour cell growth observed in our assays. 23950948_3 together our results suggest that mir-105 inhibits prostate tumour cell growth in part via its ability to downregulate the expression of the important cell cycle regulator cdk6. 25436421_1 thus, our data strongly suggest that smad7 is a target of mir-520g in hcc. 25436421_2 smad7 is identified as a functional target of mir-520g and is down-regulated in hcc specimens 26386648_2 4, the mir-198 mimic had a potent repressive effect on the mirna sensor control in htr-8/svneo cells, but virtually no effect on the fstl1-luc construct, suggesting that fstl1 is not a direct target of mir-198 in these cells. 22615562_2 these data suggest that mir-27b target ksrp and modulates inos mrna stability following c. 22615562_4 coupled with the upregulation of mir-27b in infected cells, the above data suggest that aggravation of mir-27b-mediated translational repression is involved in c. parvum-induced ksrp protein expression. 25466411_1 in vivo studies showed that overexpression of mir-150 in mice resulted in improved cardiac function, reduced myocardial infarction size, inhibition of apoptosis, and reduced inflammatory ly-6c monocyte invasion levels after ami. 25466411_2 wild-type mice transplanted with mir-150 null bone marrow cells could reverse this protective effect. 20133739_1 stable transfection of mir-19a significantly decreased the expression of a reporter gene controlled by a conserved 3'-untranslated region of the cyclind1 gene and also the protein level of cyclin d1. 20133739_3 luciferase assays showed that the cyclin d1 reporter, but not the mir-report control, was suppressed in rf-mir-19a. 20133739_4 no significant difference in cyclin d1 mrna levels was observed between the ea.hy.926 cells with stable mir-19a expression and the control cells , indicating that mir-19a regulates cyclin d1 gene expression at the posttranscriptional rather than the transcriptional level. 20133739_5 taken together, these results suggested that mir-19a repressed cyclin d1 through a specific 3'-utr binding site. 18758459_3 here we found that mir-19, mir-101 and mir-130 co-regulate ataxin1 levels and that their inhibition enhanced the cytotoxicity of polyglutamine-expanded atxn1 in human cells. 26261520_1 according to the analysis, all three programs predicted that a binding sequence in the 3'-utr of tnfaip1 was a very good match for the mir-15a seed . 26261520_2 the bioinformatics analysis thus indicated a potential functional link between tnfaip1 and mir-15a. 26261520_3 these data suggest that mir-15a may inhibit tnfaip1 expression by targeting its 3'-utr. 26261520_4 these data provide strong evidence that tnfaip1 is a specific target of mir-15a in osteosarcoma cells. 25301729_1 taken together, our current data demonstrate that mir-638 functions as a tumor suppressor in human crc by inhibiting tspan1, and that tspan1 is a potential prognostic factor for crc. 25301729_2 subsequent mechanism analyses revealed that mir-638 inhibited crc cell growth, invasion and cell cycle progression by targeting tspan1. 25301729_3 tspan1 protein levels were upregulated in crc samples and were inversely correlated with mir-638 levels. 25301729_4 mir-638 posttranscriptionally reduces tspan1 expression by targeting its 3'-utr. 25301729_5 in agreement with these results, the endogenous tspan1 protein levels were also decreased in mir-638-overexpressing crc cells and could be restored in mir-638-depleted crc cells . 25301729_6 tspan1 levels are negatively correlated with mir-638 expression and crc survival 24068960_1 figure 5 myocardin is a primary target of mir-1 in the embryonic heart. 24068960_2 furthermore, these results indicated that increased abundance of myocardin transcripts is due to mir-1 mediated repression and not caused by general up-regulation of the smooth muscle program. 24068960_3 taken together our results suggested that myocardin represents a primary target for mir-1 and kcnmb1 for mir-133a mirnas in vivo at e10.5. 24068960_4 as expected, mir-1 overexpression resulted in a significant reduction of myocardin mrna and protein while mir-133a overexpression caused a significant decline of kcnmb1 mrna and protein concentrations compared to mirna controls . 24068960_5 taken together, our results suggest that mir-1 mediated repression of myocardin limits transcriptional activation of both mir-1 and mir-133a clusters thereby adjusting its expression in a negative feedback loop . 21533124_1 luciferase reporter assays demonstrated that let-7f directly binds the 3'utr of myh9, which codes for myosin iia, and real-time pcr and western blotting further indicated that let-7f downregulated the expression of myosin iia at the mrna and protein levels. 21533124_2 in an effort to determine whether myosin iia is regulated by let-7f through direct binding to its 3- utr, we constructed full-length wild-type and mutant fragments of myh9 mrna 3- utr, and inserted them into the region immediately downstream of a luciferase reporter gene . 21533124_3 these data support that myh9 is direct target of let-7f. 21533124_4 these data demonstrate that let-7f can down-regulate the mrna expression of myh9 and can repress protein translation of it. 26309565_1 sox9 was found to be a target of mir-206. 26309565_2 sox9 was found to be a target of mir-206, and down-regulation of sox9 by shrna performed similar effects with overexpression of mir-206 in nsclc cells. in this study, we detected low mir-206 expression and identified sox9 as a mir-206 target in nsclc. 26269116_1 real-time pcr and western blotting analyses revealed that cdx2 overexpression caused inflation of mir-615-5p and depression of insulin-likegrowthfactor2 ,a direct target of mir-615-5p. 26269116_2 together, these results indicate that igf2 is a direct target of mir-615-5p in pancreatic adenocarcinoma cells and cdx2 affects the expression of igf2 via regulating mir-615-5p. 26269116_3 moreover, we verified that mir-615-5p, a direct downstream target of cdx2, inhibited proliferation by directly binding to the 3'-utr of igf2 in pancreatic adenocarcinoma cells. 21926171_1 by using mir array-based screening, we observed mir-200a silencing in breast cancer cells and demonstrated that upon re-expression, mir-200a target the keap1 3'-untranslated region , leading to keap1 mrna degradation. 21926171_2 however, co-transfection of mir-200a expression vector did not significantly alter mutant keap1 3'-utr reporter activity . 21926171_3 this result provides validation that mir-200a target the predicted site within the 3'-utr of keap1 mrna. 21926171_4 collectively, these results demonstrate that mir-200a target the 3'-utr of keap1 mrna, resulting in destabilization of keap1 mrna and a corresponding decrease in keap1 protein levels. 21926171_5 together, these findings demonstrate that mir-200a regulation of keap1 results in up-regulation of nrf2 and nrf2 translocation into the nucleus, where nrf2 functionally activates the transcription of targetantioxidant response genes, including nqo1. 21926171_6 this indicates that saha treatment of breast cancer cell lines results in the down-regulation of keap1 specifically through actions of mir-200a and provides evidence supporting endogenous mir-200a targeting of keap1. 22209977_1 overexpression of mir-181a in hl-60/ara-c cells sensitized the cells to ara-c treatment. 22209977_2 furthermore, bcl-2 was confirmed as a direct mir-181a target by immunoblot analysis and reporter gene assays. 25576220_1 here, we show that mir-124 influences gc-induced apoptosis bydirectly targeting pde4b. 25576220_2 stable expression of mir-124 in diffuse large b celllymphoma cell lines diminished pde4b expression. 26872369_1 these results demonstrate that trim29 is a target for mir-335-5p and mir-15b-5p, and that trim29 overexpression is caused by downregulation of mir-335-5p and mir-15b-5p in npc. 26623719_1 figure 2: ccng1 is a target gene of mir-27b. 26623719_2 as shown in figure 2e, the expression level of mir-27b inversely correlated with the quantity of ccng1 mrna. 26623719_3 these results confirmed that mir-27b regulates mdr by targeting ccng1. 19144909_1 mir-16 directly interacts with a site in the vegf 3'utr. 19144909_3 elisa was used to determine if the level of mir-16 affected the level of vegf. 19144909_4 while these experiments demonstrate that the mir-16 binding site within the 3'-utr of vegf is required for translation inhibition by mir-16, they do not address whether or not this regulation is functional in the context of the ires-containing 5-睻tr of vegf. 23516523_1 fluorescence reporter assays showed that mir-181a effectively binds to the 3'-utr of il1a. 23516523_2 these results indicate that mir-181a regulates inflammatory responses by directly targeting the 3'-utr of il1a and down-regulating il1a levels. 23516523_3 these results suggest that mir-181a specifically binds to the il1a 3'-utr. 19839049_3 recent evidence demonstrates that up-regulation of e-cadherin by microrna-200b and mir-200c through direct targeting of transcriptional repressors of e-cadherin, zeb1 and zeb2, inhibits epithelial-to-mesenchymal transition , a crucial process in the tumor progression. 19839049_4 we demonstrate that microrna mir-200 family-mediated transcriptional up-regulation of e-cadherin in mesenchymal mda-mb-231 and bt-549 cells is associated with direct translational repression of zeb1 and with indirect increased acetylation of histone h3 and the e-cadherin promoter. 19839049_5 the increase in histone h3 acetylation may be attributed to the disruption of repressive complexes between zeb1 and histone deacetylases and to the inhibition of sirt1, a class iii histone deacetylase. 19839049_7 additionally, disruption of zeb1-histone deacetylase repressor complexes and down-regulation of sirt1 histone deacetylase up-regulate pro-apoptotic genes in the p53 apoptotic pathway resulting in the increased sensitivity of cancer cells to the chemotherapeutic agent doxorubicin. 22387901_2 aifm3 downregulation by sirna attenuated radiation induced apoptosis in mir-210 downregulated hypoxic human hepatoma cells. 21329664_2 rb1 mrna was decreased about 30% in panc-1 cells demonstrating that mir-132/-212 down regulates rb1 protein by both mrna degradation and translational repression. 21329664_3 fig. 1 mir-132 and mir-212 are over-expressed in pancreatic tumor tissues and targetrb1. 26768135_1 the interaction between mir-25 and 3- -untranslated region of fas mrna was confirmed by dual-luciferase reporter assay. 26768135_2 moreover, fas was predicted and identified as a target gene of mir-25. 26768135_4 5b, mir-25 overexpression significantly inhibited luciferase activity in the wt group, demonstrating that mir-25 could interact with fas and therefore suppress the expression of fas. 26768135_5 hence, fas was proved to be the target gene of mir-25. 26873866_1 bioinformatics analysis revealed that mmp-9 was the potential target of mir-183 and it was found that mmp-9 was remarkably up-regulated in cervical cancer. 26873866_2 furthermore, a dual-luciferase reporter assay showed that mmp-9 as a target of mir-183 . 26873866_3 fig. 4. a. validating the predicted binding sites between mir-183 and mmp-9. 26873866_4 these data indicated that mir-183 directly regulates mmp-9 expression levels. 26873866_5 these results further confirm that mir-183 binds to the 3'-utr of mmp-9 mrna and thus regulates its expression. 26873866_6 these findings indicated that mir-183 may directly regulate the expression of mmp-9. 26556542_1 bioinformatics coupled with luciferase and western blot assays also revealed that mir-590-3p inhibited expression of zeb1 and zeb2, which are master regulators of tumor metastasis. 26556542_2 our study first indicates that mir-590-3p functions as a suppressor of gbm emt and metastasis by targeting zeb1 and zeb2, and it may be a therapeutic target for metastatic gbm. 26556542_3 we identified zeb1/2 as a direct target of mir-590-3p. in addition, real-time pcr and western blot analysis were performed for the zeb1 and zeb2 mrna and proteins in u87mg and t98g cells, confirming that mir-590-3p negatively regulates zeb1 and zeb2 expression by directly targeting their 3 ' utr regions. 26556542_4 these results confirm that zeb1 and zeb2 are regulated by mir-590-3p and mir-590-3p down-regulation, and may participate in gbm carcinogenesis and progression through potentiation of zeb1 and zeb2 expression. 26183397_1 in the sh-hotair combined with mir-326 mimics group, the fgf1 expression was reduced in both mrna and protein levels .5d. however, mir-326 inhibitors restored the low expression levels of fgf1 inducing by hotair knockdown .5d. these results suggested that hotair knockdown inhibited the fgf1 expression by up-regulating mir-326. 26183397_2 results showed that mir-326 mimics down-regulated the fgf1 expression, while mir-326 inhibitors up-regulated it .5f. furthermore, the luciferase reporter assay showed that the co-transfection of pre-mir-326 and fgf1-wt strongly decreased the luciferase activity, but the co-transfection of pre-mir-326 and fgf1-mt did not change it .5g. these results suggested that fgf1 was a direct target of mir-326. 26242259_1 in addition, we also verified a direct interaction between mir-124 and 3'-utr of grb2. in the current study, we reported a novel regulation of malat1 over the expression of mir-124 and verified a new target of mir-124, grb2, in regulating growth and invasion of hr-hpv cervical cancer cells. 26242259_3 in the present study, we verified a direct interaction between mir-124 and 3'-utr of grb2. 26575700_1 we focused on ror1 as the primary candidate target of mir-382, and examined firstly the direct binding between mir-382 and ror1, we constructed the vectors ror1-3'-utr and mut-ror1-3'-utr to observe their binding activity with mir-382. 26575700_3 together, these data provide strong evidence that ror1 is a specific target of mir-382 in ovarian cancer cells. 26722446_1 here, we show that microrna-214 interacts with the 3- -untranslated region of pcbp2 mrna and induces its degradation, leading to reductions in its protein expression. 26722446_2 the results from our study indicate that mrna and protein levels of pcbp2 are negatively regulated by mir-214. 23867156_3 taken together, these results suggest that mff is a specific target of mir-761. 26232411_3 six out of the seven tested targets were repressed following mir-58.1 or mir-80 transfection in a site-specific manner, suggesting that indeed they are repressed by mir-58 family in vivo and that the mir-58 target site is necessary for repression . 26232411_4 this conclusion is further supported by the recent demonstration that the pmk-2 p38 mapk, for which we had detected 1.5, 2.3 and 4.8 fold upregulation in mir-58.1 single, mir-80; mir-58.1 double and mir 80; mir-58.1; 26232411_5 mir-81-82 quadruple mutant samples, is a bona fide mir-58 family target . 26264654_1 figure 4. mir-544a directly binds to the 3'-utr region of cdh1 and induces the nuclear import of -beta-catenin. 26264654_2 we detected statistically significant reductions in luciferase activity in wild-type constructs and not in mutant constructs in region 2, whereas mir-544a could not bind to region 1 , indicating that cdh1was a direct target of mir-544a. 26264654_3 taken together, our findings suggested that mir-544a induces the nuclear import of -beta-catenin and suppresses e-cadherin and axin2, resulting in the induction of emt through the activation of tcf/lef . 26264654_4 figure 5. mir-544a directly targets both cdh1 and axin2 and may activate the wnt signaling pathway. 25727016_1 microrna-301a modulates doxorubicin resistance in osteosarcoma cells by targeting amp-activated protein kinase alpha 1. luciferase reporter assay identified ampkalpha1 as direct target gene of mir-301a. 25727016_2 notably, mir-301a reduced doxorubicin-induced cell apoptosis whereas anti-mir-301a enhanced apoptosis in os cells, suggesting that up-regulation of mir-301a contributed to chemoresistance of os cells. 26450708_1 these data indicate that mir-139 is an important direct post-transcriptional regulator of mcpip-1 and indirect post-transcriptional regulator of il-6 expression in oa chondrocytes in vitro. 26450708_2 overexpression of mir-139 inhibitor in oa chondrocytes significantly increased the expression of mcpip1 mrna . in contrast, overexpression of mir-139 decreased the levels of mcpip1 transcripts in the transfected oa chondrocytes . 26450708_3 this data confirms that mir-139 interacts with the 'seed sequence' located in the 3- utr of the mcpip1 mrna. 20976200_1 using 2'-o-methylated antisense oligonucleotide, we confirmed that the cxcl16 reporter regulation by mir-m23-2 could be inhibited in a sequence specific manner. 23274497_1 using a combined bioinformatics approach, gene set enrichment analysis, and mirna target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including becn1, bnip3l, atg12, atg5, and atg2. 20309945_1 therefore, we suggest that hsa-let-7g may act as a tumor suppressor gene which inhibits hcc cell proliferation by down-regulating the oncogene, c-myc, and up-regulating the tumor suppressor gene, p16ink4a. 20309945_2 c-myc as a downstream target of hsa-let-7g. 20309945_3 effects of hsa-let-7g on the transcriptional and translational expression of p16. 20309945_4 our results indicate that the c-myc is a plausible targetfor hsa-let-7g and an over-expression of hsa-let-7g might inhibit cell proliferation in hcc cells via downregulating the mrna and protein expression of c-myc. in fact, the hsa-let-7g gene may function by targeting the 3'-utr of c-myc mrna, thus induced mrna degradation and translational repression. 20309945_5 taken together, our data suggested that hsa-let-7g regulated hcc cell proliferation through direct targeting c-myc and indirect regulating p16 gene that was regulated by c-myc through bmi-1. 21258880_1 the luciferase activity of bcl2 3'-untranslated region-based reporter constructed in sgc7901/vcr and a549/cddp cells suggested that bcl2 was the direct targetgene of mir-497. in both sgc7901/vcr and a549/cddp cells, a significant decrease in relative luciferase activity was noted when pgl3-bcl2-3'-utr was cotransfected with the mir-497 mimic but not with the mirna mimic control, suggesting that bcl2 is the targetgene of the mir-497 . 21258880_2 since the antiapoptotic bcl2 protein is the target of the mir-497, we hypothesized that the mir-497 might modulate multidrug resistance of cancer cells by repressing the bcl2 protein expression. 21258880_3 these results showed that mir-497 might modulate multidrug resistance of cancer cells at least in part by repressing the bcl2 protein expression. 26720492_1 therefore, these results further confirmed that hmgb1 is a functional target of mir-129-5p. 26252254_1 together, these data suggest that mir-122 negatively regulates the expression of pkm2 by directly targeting its 3'-utr. 26910120_1 these data indicated that mir-34a upregulates rig-i expression by directly binding to its 3' utr in hela and c33a cells 26626315_1 in addition, cytochrome b mrna and protein levels were also decreased when mir-151a-5p was overexpressed. 26626315_2 these results indicate that mir-151a-5p may participate in the regulation of cellular respiration and atp production through targeting cytb. 26626315_3 these results indicate that mir-151a-5p negatively regulates cytb expression at a post-transcriptional level. 26136151_1 mir-203 negatively regulates the expression of sam68 by directly binding to its 3'utr. 26136151_2 these data indicated that mir-203 negatively mediated the expression of sam68 in nb cells 20878113_3 furthermore, caspase-10 was shown to be a target of mir-186* regulation. 26035427_1 we demonstrated that mir-153 downregulated snail expression by directly targeting the 3'-untranslated region of snail. 26035427_2 taken together, our results suggest that mir-153 plays a critical role in suppressing emt and hcc progression by direct suppression of snail expression. 26296312_1 furthermore, we identified pten as a direct target of mir-454. 26296312_2 luciferase reporter analysis demonstrated that overexpression of mir-454 reduced luciferase activity in the pten wild-type reporter gene but not the mutant type, suggesting that mir-454 directly targeted the pten 3 ' utr . 26296312_3 these findings suggest that mir-454 may be an oncogene that controls pten expression in uveal melanoma cells. 26538392_1 in contrast, rictor did appear to be a relevant target of mir-15b/16. 20106983_2 specifically, two brain-enriched mirnas, mir-7 and mir-153, have been shown to bind directly to the 3' utr of snca mrna and significantly reduce its levels. 26408699_1 these results suggest that anril is involved in p15 repression in cancer cells, such as hela and h1299 cells. 26191163_1 to delineate the mechanism by which mir-199a reduced vegf-a production, further analysis of the target genes of mir-199a showed that mir-199a targeted both vegf-a and hypoxia- inducible factor -1alpha in escs. 26191163_2 hif1a was confirmed as a mir-199a target in cardiac myocytes . 26191163_3 figure 4a shows the 3'-utr of hif1a contains a potential target of mir-199a. 26191163_4 these results suggest that the inserted fragment of hif1a could be targeted by mir-199a. 26191163_5 we then transfected mir-199a into escs and tested the hif1a expression level. 22902544_1 mir-34a, which besides its well-established effects related to cell-cycle arrest and senescence has recently been identified as an inhibitor of autophagic flux and a direct regulator of atg9a in mammalian cells 19816956_1 overexpression of mir-21 decreased both protein and mrna levels of tgfbr2. 19816956_2 the expression of tgfbr2 was decreased during adipogenic differentiation of hascs in concordance with an increase in the level of mir-21. in contrast, inhibiting mir-21 with 2- -o-methyl-antisense microrna increased tgfbr2 protein levels in hascs, accompanied by decreased adipogenic differentiation. 19816956_3 mir-21 target the 3'utr of tgfbr2 mrna. 19816956_4 real-time pcr and western blot analyses showed that mir-21-overexpressing hascs exhibit less tgfbr2 expression and that anti-mir-21-transfected hascs exhibit increased tgfbr2 expression . 19816956_5 a luciferase reporter assay was used to demonstrate that mir-21 directly decreased tgfbr2 expression. 22544933_1 in this study, we identified microrna-494 , whose expression was dramatically induced by tumor-derived factors, as an essential player in regulating the accumulation and activity of mdscs by targeting of phosphatase and tensin homolog and activation of the akt pathway. 22544933_2 pten is a functional target of mir-494, and the pten/akt pathway is critical for the activation of mdscs. 22544933_3 these data strongly indicated that the pten expression downregulated by mir-494 is essential for the activation of mdscs. 20441582_3 the downregulation of mir-26a can relieve the suppressive effect of this mirna on il-2 expression. 26317552_1 we found that pten was a direct target of mir-10a in nsclc. 26317552_3 we suggest that mir-10a contributes to nsclc by targeting pten. 26317552_4 these results suggest that mir-10a down-regulated pten expression by directly targeting its 3'-utr. 26317552_5 taken together, we have provided further evidence that pten is a direct and functional target gene of mir-10a on nsclc. 22508479_1 a combination of mrna profiling, bioinformatics analysis and experimental validation identified metadherin as a direct target of mir-375. 22508479_3 as the majority of cancer-relevant deaths arise from resistance to therapy and metastasis, re-expression of mirna-375 or inhibition of mtdh might be potential therapeutic approaches for the treatment of tamr breast cancer in future. 22508479_4 the results of the luciferase assay confirmed that mtdh is a direct target of mir-375. 22508479_5 mutagenesis of targetsites in the 3'-utr of mtdh gene abbrogates direct targeting of mirna-375. 17906637_1 we have found that the 3'ends of hiv-1 messenger rnas are targeted by a cluster of cellular mirnas including mir-28, mir-125b, mir-150, mir-223 and mir-382, which are enriched in resting cd4+ t cells as compared to activated cd4+ t cells. 26492575_1 according to a previous report, bcl-2 is a possible target of mir-146a during autophagy , so we explored the function of bcl-2 during hypoxia-induced autophagy. 26492575_2 furthermore, additional bcl-2 decreased the autophagy caused by hif-1alpha and mir-146a in normoxia , and this phenomenon suggested that bcl-2 is the downstream factor of mir-146a for autophagy regulation. 25361012_2 found that pten was a potential target of mir-26a and mir-214, which had been confirmed following dual-luciferase reporter assays, reverse transcription polymerase chain reaction and western blotting.inhibition of mir-26a or mir-214 could induce more apoptosis in primary cultured cll cells. 25391425_2 consistent with the effects of mir-451, silencing cxcl16 could phenocopy the effects of mir-451 on phenotypes of osteosarcoma cells. 25391425_3 furthermore, cxcl16 expression was upregulated in osteosarcoma tissues and inversely associated with mir-451 in human osteosarcoma tissues. 25391425_4 our data reveal a downregulated expression of mir-451 in osteosarcoma tissues, which is inversely associated with cxcl16 levels. 25391425_5 this finding supported the hypothesis that cxcl16 was a direct, downstream target for mir-451 in osteosarcoma cells. 25489229_1 mir-34a belongs to a signaling network involving p53 and sirt-1. 25489229_3 inverse relationship between the levels of expression of mir-34a and its target sirt1 mrna was found at 18 and 24 months of age. 23585551_1 we demonstrate that mir-132/212 controls cell survival by direct regulation of pten, foxo3a and p300, which are all key elements of akt signaling pathway. 19390056_5 ectopic overexpression of mir-17/92 resulted in a strong reduction of the bmpr2 protein, and a reporter gene system showed that bmpr2 is directly targeted by mir-17-5p and mir-20a. 19390056_7 because il-6 signaling is mainly mediated by stat3 , the expression of stat3 was knocked down by small interfering rna, which abolished the il-6-mediated expression of mir-17/92. 19390056_9 promoter studies confirmed that il-6 enhances transcription of c13orf25 through this distinct region. 19390056_11 taken together, we describe here a novel stat3-mir-17/92-bmpr2 pathway, thus providing a mechanistic explanation for the loss of bmpr2 in the development of pulmonary hypertension. 22131135_1 to study the direct binding of mir-9 to this site, the 3'-utr of nf-κb1 was ligated to an egfp reporter gene and used in transcription activation assays as previously described . 22131135_2 the specificity of the mir-9 binding site was examined using constructs containing a mutated mir-9 binding site within the nf-κb1-3'-utr. 22131135_4 we found that the egfp fluorescence intensity in psuper-mir-9-transfected cells was significantly lower than in cells transfected with empty vectors , indicating that mir-9 can bind directly to sites within the nf-κb1-3'-utr. 22131135_5 this binding appears specific because the overexpression of mir-9 did not affect the egfp fluorescence intensity of the cells transfected with mutated putative mir-9 binding sites . 23155254_2 -gammah2ax foci assay showed that dna double-strand break repair was delayed in mir-34b/c transfectants. the proportion of sub-g phase cells was increased in mir-34b/c transfectants after irradiation. 23155254_3 mir-34b/c inhibited expression of cyclin-d1, cyclin-dependent kinase 4/6, b-cell lymphoma-2 and increased cleaved poly polymerase and cleaved caspase-3 after irradiation. 12459261_1 the role of ahif could be a post-transcriptional regulation of hif-1 mrna by increasing its instability via an exposition of au rich elements in the hif-1 mrna 3'utr. 12459261_2 thus, ahif would be implicated in the complex regulation of hif-1 action. 21385904_2 direct interaction between mir-218 and the 3'-utr of robo1, birc5, and gja1 was examined using the luciferase assay. 21385904_3 indeed, cotransfection experiments have shown direct regulation of these three 3'-utr regions by mir-218 , which was significantly abrogated when mutating the predicted mir-218 seed regions in the pmir-report utr constructs, thereby validating the direct interaction between mir-218 and the corresponding 3'-utrs. 25166914_1 sgpp1 and smad2 at mrna and protein levels were negatively correlated with mir-27a in human colorectal cancer tissues and cancer cell lines. 25166914_2 increased mir-27a significantly repressed sgpp1 and smad2 at transcriptional and translational levels. 25166914_3 functional studies showed that increasing mir-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-stat3 and upregulation of cleaved caspase 3. 26339371_1 we further demonstrated that mir-192 directly targeted 3'-utr of bim gene, and inhibited its protein expression. 26339371_2 taken together, these data indicated that bim was the direct target of mir-192 at least in esophageal cancer. 26339371_3 collectively, these results suggested that bim functions as a target of mir-192, responsible for mir-192 mediated regulation of the apoptosis of escc cells. 26339371_4 our present data suggest bim as a functional target of mir-192 by luciferase reporter gene assays, rt-pcr and western blot analysis method, respectively. 21113793_1 we noted that mir196b and mir205 lack expression signatures in all of the nine liver samples, whereas mir-7, mir345, mir433, and mir511 had low expression counts in all the nine liver samples.the 21113793_2 mirnas mir-7, mir196b, mir433, and mir511 target the polymerase or s gene of hbv, mir205 targets the x gene, and mir345 targets the prec gene. 20145152_1 pre-mir-181a and pre-mir-630 consistently modulated mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis, including bax oligomerization, mitochondrial transmembrane potential dissipation, and the proteolytic maturation of caspase-9 and caspase-3. 23416424_1 tregs compared to chimeric wild-type tregs, indicating that only mir-21 is an intrinsic target of bcl6 in tregs, and that mir-22 and mir-146b are not likely to be directly regulated by bcl6 in tregs.of 23416424_3 along with decreasing spry1, mir-21 mimic augmented gata3 mrna . 23416424_4 il12a, another reported mir-21 gene target in myeloid cells is involved in th1/th2 polarization . in tregs, il12a is a component of the treg suppressive cytokine il-35 in conjunction with ebi3 . 23334332_1 furthermore, we characterized rac1 as a direct target of mir-124, and mir-124 interacted with the 3- -untranslated region of rac1, which we showed to be a putative tumor promoter in pancreatic cancer. 23334332_2 in addition, we characterized rac1 as a direct target of mir-124 and demonstrated that mir-124 interacts with the 3- -untranslated region of rac1 to mediate its tumor-suppressive effect on cellular proliferation and invasion. 23334332_3 in the current study, we identified rac1 as a direct and functional target of mir-124. 26090579_1 we validated proapoptotic proteins bcl2l11 and cdkn1c as mir-221 targets suggesting that ifn-alpha can induce dc apoptosis via mir-221 downregulation. 26090579_3 out of the 6 mrnas, bcl2l11, cdkn1c, and socs1 were finally validated as mir-221 targets . in addition, we have validated mir-221 targets: bcl2l11, cdkn1c, and socs-1 in mdcs and demonstrated that mir-221 overexpression in mdcs leads to enhanced secretion of il-6 and tnf-alpha. 19118166_1 mir-9* target the 3'utr of corest. 19118166_2 cotransfection of the corest 3'utr reporter plasmid and 5 or 15 nm pre-mir-9* reduced reporter expression compared with controls =41.612, 19118166_4 also, only pre-mir-9* significantly reduced endogenous corest expression in hek 293 cells =11.173, p<0.0036 . 26219083_1 this provided us with 28 genes of which some have been previously experimentally furthermore, we found that stable inhibition of the highly expressed mir-124 and mir-125 in hippocampal neurons led to significant but distinct changes in the ago2 binding of target mrnas, resulting in subsequent upregulation of numerous mirna target genes. 26219083_3 as mir-124 targets, including nuclear receptor subfamily 4, group a, member 1 , which displayed both reduced ago2 binding and increased mrna levels after mir-124 inhibition . 20005803_1 fog2 is targeted by mir-200 to regulate pi3k-akt. 20005803_2 these data demonstrate that fog2 is an authentic target of endogenous mir-200 mirnas. 20005803_3 there is generally a negative correlation between mir-200 mirnas and fog2 in a given tissue type, consistent with a suppressive role for mir-200 in fog2 regulation. 20005803_4 these data demonstrate that fog2 is an authentic target of endogenous mir-200 mirnas. in a screen for mirnas that modulate cell proliferation, we observed that human mir-200 mirnas promote cell growth when transfected into several human cell lines . 26636540_2 these results suggest that mir-145 can induce post-transcriptional silencing of its targeted genes by binding to the nanog mrna 3'-utr or ror specific sites. 26636540_3 our study had confirmed that nanog is a direct target of mir-145 . 20709030_1 these results suggested that both mir-106b and t-betar ii are abnormally expressed in our ad mouse model. 20709030_2 the analysis revealed that two putative binding sites for mir-106b in the 3- utr of the t-betar ii mrna . 20709030_3 to confirm the association between mir-106b and t-betar ii, we detected t-betar ii levels in vitro through mir-106b overexpression or underexpression. 20709030_4 we constructed a cell line stably transfected with mir-106b, wherein mir-106b levels were 4.7-fold increased compared with cells stably transfected with the control vector . 20709030_5 our results showed that t-betar ii mrna levels were unchanged , indicating that mir-106b blocks t-betar ii protein translation but does not promote degradation of t-betar ii mrna. 20709030_6 to investigate the potential interaction between mir-106b and t-betar ii, the wild-type 3- utr of the t-betar ii sequence as well as two single mutants and one double mutant of the t-betar ii 3- utr were subcloned downstream of the renilla luciferase coding sequence and the vector construct was cotransfected into 293t cells along with the mir-106bexpressing vector or negative control vector. 20709030_8 these results indicated that mir-106b regulates t-betar ii by binding to the first putative binding site in the 3'-utr of t-betar ii; the second putative binding site does not appear to play a role in the suppression of t-betar ii expression. 25122182_1 we found that denv infection could induce mir-30e* expression in denv-permissive cells, and such an overexpression of mir-30e* upregulated ifn-beta and the downstream ifn-stimulated genes such as oas1, mxa and ifitm1, and suppressed denv replication. 22228753_1 using luciferase reporter assays, we assessed the impact of mir-17 on npas3 translation and demonstrated that mir-17 alters npas3 biosynthesis by binding to the npas3 3'untranslated region . 22228753_2 these findings suggest that mir-17 may directly regulate npas3 expression and we suggest this could lead to an increase in npas3 mrna turnover and decreased npas3 protein synthesis. 22228753_3 consistent with observations using the endogenous npas3 3'utr in neuronal cells, we showed that mir-17 decreases luciferase reporter activity in cells transfected with constructs containing the wild-type mir-17 binding sequence in the luciferase 3'utr . 22157681_1 here we report that mir-30b/c and mir-221/222, modulated by both egf and met receptors, and mir-103, -203, controlled only by met, play important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of nsclc cells, in vitro and in vivo, by inhibiting the expression of bim, apaf-1, pkc-蔚 and src genes. 21228352_1 luciferase reporter assay showed that mir-214 specifically binds the phosphatase and tensin homolog mrna 3'-untranslated region, implicating pten as a targetgene of mir-214. 21228352_2 the inverse correlation between mir-214 and pten expression levels in thp-1 cells or monocytes treated with ages, as well as monocytes from crf patients, further supports the conclusion that monocytic pten is one of the targetgenes of mir-214. 21228352_3 furthermore, the effect of bsa-ages on serum deprivation-induced thp-1 cell apoptosis was largely abolished by transfecting thp-1 cells with anti-mir-214, implying that the role of bsa-ages in delaying monocyte apoptosis is through modulation of mir-214-targeting pten. 23818585_1 microrna-18a and microrna-421, both of which target atm, are positively controlled by mtor signaling. 23818585_2 these results indicate that mir-18a and mir-421 are positively controlled by mtor-mediated signaling pathways. 23818585_3 thus, the up-regulation of mir-18a and mir-421 might contribute to, at least in part, the down-regulation of atm in solid pediatric tumor xenografts. 25963903_2 furthermore, the results of luciferase assay indicated that mir-9 could directly target 3'-utrs of notch1 . 25963903_3 by performing luciferase assay and the evaluating the effect of mir-9 expression on different 3'-utrs , we identified a significant effect of mir-9 on down-regulation of luciferase activity of notch1 3'-utr. 21586285_1 recently, tnc was reported to be a target of mir-335 in the research of tumor metastasis. 21586285_2 therefore, we examined the effects of overexpression of mir-335 on tnc expression in hscs. 21586285_4 following transfection with mir-335, tnc expression in hscs was decreased by 76% and 74% tested by qrt-pcr and western blot assays respectively , demonstrating that tnc expression was negatively regulated by mir-335 in hscs. 19632201_1 mir-34s have been characterized as direct p53 targets, which induce apoptosis, cell cycle arrest, and senescence. 19632201_3 thus far, there is no study on the role of mir-34s in osteosarcoma. 19632201_6 and p53 also partially contributes to the mir-34s induced cell cycle arrest and apoptosis. 22498306_1 luciferase reporter gene assays confirmed that mir-199a targets cd44 via an mir-199a-binding site in the 3'-utr. 22498306_2 the luciferase activity of the report gene with cd44 3'-utr was significantly inhibited by mir-199a, whereas the luciferase activity of the report gene with the mutated cd44 3'-utr was not affected by mir-199a . 22498306_3 these results demonstrated that mir-199a can target cd44 mrna by specifically binding to the cd44 3'-utr. 22498306_4 these data indicated that exogenous mir-199a downregulated the expression of endogenous cd44 in cd44+/cd117+ ovarian cics. 22498306_5 these results implied that reduced expression of cd44 via overexpression of mir-199a could significantly attenuate the invasion and migration of cd44+/cd117+ ovarian cics. 22498306_6 herefore, reduced expression of endogenous cd44 in cells overexpressing mir-199a influences the stemness of cd44+/cd117+ ovarian cics. in conclusion, we report that mir-199a targets cd44 and reduces the proliferation and invasion of cd44+/cd117+ ovarian cancer stem cells in vitro and in vivo. 21357793_2 hence, an association was established between mir-200b downregulation and vegf upregulation in dr. 21357793_3 these results established a direct regulatory relationship between mir-200b on hg-induced vegf expression and its functional consequences. 21357793_5 mutated targetsequence vegf 3'-utr was also not responsive to mir-200b . 23094093_1 the expression of two of the known mir-223 target, mef2c and rhob, was highly reduced in pi treated as well as mir-223 over-expressing vsmcs. 23094093_2 finally, we show strong reduction in the expression of two of mir-223 target, mef2c and rhob, which have established roles in vsmc biology. 23094093_3 figure 5 effect of mir-223 up- and down regulation and pi on mir-223 specific target mef2c and rhob. 21113131_2 nkrf was found downregulated and mir-301a upregulated in human pancreatic adenocarcinoma tissues. 21113131_3 neither nkrf expression level nor nf-kappab reporter activity was affected by mir-130a, indicating that the complementation of 3- part of mir-301a to 3'-utr of nkrf is essential for nkrf-negative regulation. 21113131_4 thus, we conclude that the interaction of mir-301a and nkrf represents a 3- compensatory site and the first one with two g:u pairs. 21113131_5 these results indicate that overexpression of mir-301a down-regulates nkrf protein levels and that down-regulation of nkrf by mir-301a is dependent on the nkrf 3'-utr. 21113131_6 this result indicated that mir-301a may targetother genes beyond nkrf to regulate nf-kappab activation. 23280823_1 taken together, our findings suggest that ebv encoded mir-bart3* mirna targets dice1 tumor suppressor to promote cellular growth and transformation in npc.enforced expression of mir-bart3* or its precursor pre-mir-bart3 led to down-regulation of endogenous dice1 expression. 26497855_1 collectively, these data suggest that mir-1 may inhibit the wnt/-beta-catenin signaling by reducing the frizzled 7 and tnks2 expression in breast cscs. 18577589_1 human hd cortices have increased levels of the mir-132-targetmrna, p250gap. 18577589_2 our finding that mir132 target the p250gap mre in a heterologous reporter system and that an intact seed sequence is required for mir132-mediated repression suggests that p250gap is a direct mir132 target this finding was confirmed by showing that overexpression of mir132 in hippocampal neurons down-regulated endogenous p250gap . 26349986_1 inhibition of mir-155 activity reduces ifn-gamma and il-17 expression in dlnc 24551047_3 all mirnas inhibited reporter activity in assays with the pax5 3'utr reporter including mir-138 . 26221592_1 among them, runx1 and mef2c have been already validated as direct mir-27 targets . 26221592_4 figure2 shows that overexpression of mir-27 selectively results in downregulation of both mef2c and runx1 in cardiomyocytes and skeletal myoblasts , whereas no significant changes were observed upon mir-125 overexpression. 26221592_5 interestingly, selectively overexpression of mir-27 leads to downregulation of mstn in hl1 atrial cardiomyocytes but not in sol8 skeletal muscle myoblasts, as illustrated in figure3. 17656095_1 using gene-expression analyses, reporter gene assays, and chromatin-immunoprecipitation approaches, we present definitive evidence that the abundance of the three-member mirna34 family is directly regulated by p53 in cell lines and tissues. 22250746_1 mcas acts as a sequence-specific translational initiation inhibitor by targeting the ss-1 region of the csgd 5'-utr. 19015276_1 these abnormalities can be attributed, at least in part, to elevated expression of srf and cyclin d2, which are target for repression by mir-133a. 19015276_2 the regulation of mir-133 by srf and the targeting of srf by mir-133 provide a negative feedback loop to precisely titrate the actions of srf such that elevations of srf activity enhance the expression of mir-133a with consequent dampening of srf expression. 17998940_1 microrna-218 was specifically underexpressed in hpv-positive cell lines, cervical lesions and cancer tissues containing hpv-16 dna compared to both c-33a and the normal cervix.expression of the e6 oncogene of high-risk hpv-16, but not that of low-risk hpv-6, reduced mir-218 expression, and conversely, rna interference of e6/e7 oncogenes in an hpv-16-positive cell line increased mir-218 expression. 17998940_2 we also demonstrate that the epithelial cell-specific marker lamb3 is a target of mir-218. 17998940_3 we also show that lamb3 expression is increased in the presence of the hpv-16 e6 oncogene and this effect is mediated through mir-218. 18073197_1 mir-bart2 guides cleavage within the 3'-untranslated region of balf5 by virtue of its complete complementarity to its target. . 26054847_1 transfecting cells with the r11-sspei/mir-145 complex showed that ectopic mir-145 in human prostate cancers significantly repressed the luciferase activity of reporter plasmids carrying the fscn1, c-myc, igf-ir and muc13. 21917858_1 taken together, these results given above, confirmed that mir-145 decreased hif-1α and vegf expression by targeting p70s6k1. 21917858_2 these results suggest mir-145 inhibits the expression of hif-1alpha and vegf by targeting p70s6k1. 21917858_3 these initial experiments indicate that mir-145 negatively regulated p70s6k1 expression. 16513633_3 using rsex as bait, two of its targets,ompa and ompc mrna were captured. 16513633_4 rsex overproduction results in reduced amounts of ompa and ompc mrna and corresponding outer membrane proteins. 16513633_5 the absence of both ompa and ompc itself allows survival to rsep depletion independently of rsex. 20737575_1 the authors demonstrated that mir-145 target a putative microrna regulatory element in the 3'- untranslated region of fli1. 20737575_2 taken together, these data suggest that the mir-145 binding site present in the fli1 3'-utr is critical for mir-145-mediated gene regulation. 20737575_3 the inverse correlation suggests that mir-145 and fli1 are coordinately regulated in the development of tumors. 20737575_4 these results suggest that mir-145 target fli1 by functioning on translational regulation. 16717284_2 if we consider fecd a correct prediction, 1 out of 26 predictions for omra is supported by the microarray data. 22144581_2 taken together, these results identify glua2 mrna as a genuine target gene of mir-181a in primary rat neurons. 22144581_3 intriguingly, other glua receptors lack canonical mir-181a binding sites in their 3'-utrs, suggesting that mir-181a selectively targets glua2 for translational repression. 26191180_1 these all results suggested that, mir-302a could combine with the specific sdc1 mrna 3'-utr binding sites and play a role in inhibiting the expression of sdc1 gene. 26191180_2 all these data suggest that mir-302a negatively regulates the expression of sdc1 through mrna cleavage mechanism at the post-transcriptional level. 25704079_1 figure 2a demonstrates a high throughput gene expression array analysis of some of the validated targets of mir-21 in rpmi ebvgfp cl-12. 25704079_2 p21 is a tumor suppressor gene and a validated target of mir-21.17 26020378_1 taken together, we concluded that bmi-1 is a genuine target of mir-495. 21983127_1 mir-150 directly target the 3'utr of muc4 to suppress its expression. 21983127_2 our data suggest that mir-150 downregulates muc4 expression through a posttranscriptional mechanism. 21983127_3 thus, our data strongly suggest that mir-150 negatively regulates the expression of muc4 by directly targeting the 3- utr of muc4 transcript. 21983127_4 altogether, our data suggest that mir-150 represses her2 and its downstream signaling through muc4 downregulation in pc cells. 21983127_5 our findings, thus suggest that mir-150-mediated inhibition of growth and clonogenicity in pc cells may, in part, be due to downregulation of muc4 expression. 21983127_6 our study confirms the clinical relevance of our experimental data on mir-150-mediated muc4 regulation in pc cells. 21983127_7 furthermore, our results provide an evidence for a clinical correlation of mir-150 and muc4 expression in a small subset of malignant pancreatic tissues, whereas muc4 in normal pancreas primarily seemed to be regulated by transcriptional mechanisms. 23900885_1 by using bioinformatics analysis, we found that mir-181b, one of 19 differentially expressed mirnas, may target aconitate hydratase , heat shock protein a5 , and ubiquitin carboxyl-terminal hydrolase isozyme l1 among 26 changed protein kinase c isoform-specific interacting proteins in hpc mouse brain. 23900885_2 by using a t7 promoter-driven control dual luciferase assay, we confirmed that mir-181b could bind to the 3'-untranslated rergions of hspa5 and uchl1 mrnas and repress their translations. 23900885_3 these results suggest that the downregulated mir-181b induces neuroprotection against ischemic injury through negatively regulating hspa5 and uchl1 protein levels, providing a potential therapeutic target for ischemic stroke. 26783726_1 tnfaip3 was predicted as the target of mir-18a, and hif1a, vegfa, igf1r, and igf2 were predicted as the targets of mir-199a-5p. 26783726_3 anti-mir-18a inhibitor significantly augmented the luciferase signal of the vector containing the target site of tnfaip3. 26783726_4 pre-mir-199a-5p precursor significantly suppressed the luciferase signals of the vectors including the target sites in hif1a, vegfa,igf1r, and igf2 mrnas . 26783726_5 similarly,western blot analyses revealed that anti-mir-18a augmented tnfaip3 expression in plc/prf/5 cells. 26783726_6 pre-mir-199a-5p suppressed the expression of hif1a and vegfa in huh7 cells, the expression of igf1r and igf2 in hep3b cells, respectively . 18801338_1 igf-1 inhibits glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis and igf-1's effect is regulated by mir-1. 19136465_2 similar results were obtained with mtg-amo1/133 on mir-1 and mir-133 in lysate from control untreated h9c2 cells . 24556602_1 this is the first study showing that mir-27a can function as an oncogene by targeting map2k4 in the osteosarcoma mg63 cell line. 24556602_2 these results demonstrated that map2k4 is a potential target of mir-27a and can be directly regulated by mir-27a. 23710609_3 importantly, our data showed that mir-145 downregulated the expression of c-myc and cdk6, which have previously been identified as two direct targets of mir-145. 24895573_2 moreover, mir-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various egfr targeting agents. 24895573_4 in conclusion, mir-146a plays a vital role in the cell growth and apoptosis of hcc cells and inducing mir-146a level might be a critical targeted molecular therapy strategy for hcc. 21762377_1 we found the microrna mir-145 binding to three different motifs of the 3'-utr mrna dab2 region. 21762377_2 as shown in figure 2a-c, dab2 levels are decreased as a function of time after tgf--beta1 treatment and this decrease correlates with an up-regulation of mir-145. 22834685_1 mir-185 was found to regulate several important genes, including cdc42, rhoa, vegfa, cyclin-dependent kinase 6 ,dna -methyltransferase 1 , b-cell leukemia/lymphoma 2 . 22834685_2 thus, mir-185 regulated vegfa by cdc42 and rhoa. 22834685_3 therefore, we focused on the affects of mir-185 on glioma cells invasion by targeting cdc42 and rhoa. 22834685_4 low expression of both lrrc4 and mir185 was significantly associated with a shorter overall survival . 22834685_5 together, these data indicate that lrrc4 can inhibit glioma cell invasion by increasing mir-185 expression, and that mir-185 targets cdc42 and rhoa directly as well as vegfa, vimentin, and gfap indirectly both in vivo and in vitro. 24686007_2 inhibition of mir-489 yields the opposite results. in addition, mir-489 overexpression increases the sensitivity of skov3/cddp and ovcar3/cddp cells to cddp and inhibits their colony number. 24686007_3 akt3 is validated as a direct target of mir-489 in skov3, ovcar3, skov3/cddp and ovcar3/cddp cells. in addition, mir-489 suppresses akt3 protein expression by binding sites on its 3'utr. 24686007_4 knockdown of akt3 results in a similar effect as that because of mir-489 overexpression; importantly, akt3 silencing rescues the functions induced by mir-489. 26253106_1 here, we mainly focused on mir-181a to further investigate the interaction between meg3 and mir-181a in gc cells. 26253106_2 these data demonstrated that mir-181a could bind to meg3 and meg3 could function as a cerna in gc cells. 26253106_3 to validate whether mir-181a targets bcl-2 in gc, immunoblotting assay was carried out and showed that bcl-2 was about 2-fold higher in hgc-27 cells transfected with mir-181a inhibitor compared with the control . 26253106_4 because meg3 shared regulatory mir-181a with bcl-2 mrna, we wondered whether meg3 could modulate bcl-2 in gc cells. 26253106_5 all these results suggest an important role of meg3 in modulating bcl-2 by competitively binding mir-181a. 26375442_1 to investigate whether mir-130a and mir-495 could bind directly to the 3'-utr of runx3 mrna to decrease runx3 expression, we cloned these mirnas target site in the 3'-utr of runx3 into the luciferase expressing pgl3-control vector just downstream of the luciferase open reading frame .4a. combination of mir-130a and mir-495 synergistically downregulated runx3 reporter activity .4b. these results indicate that mir-130a and mir-495 impair runx3 mrna translation by directly binding to the 3'-utr of runx3. 21242962_1 upa is the targetgene for mir-23b as the mir repressed upa expression and interacted with the 3'-untranslated region of upa mrna. 21242962_2 by western blot analysis, ectopic mir-23b expression resulted in a reduction and mir-23b inhibition led to an elevation of upa protein level in siha cells . 21242962_3 this confirms the targeting effect of mir-23b on upa mrna. it also verifies that the influence of mir-23b on cell migration in human cervical carcinoma cells is through upa. the results suggest the role of p53 in the regulation of mir-23b/upa in siha cells. 21242962_4 this supports the involvement of p53 in the hpv-16 e6 regulation of mir-23b/upa in siha cells. 22170610_1 the mir-126 direct targetgenes igfbp2, pitpnc1 and mertk are individually required for endothelial recruitment and metastatic colonization, are downstream of mir-126 and individually correlate in expression with human metastatic progression. 22170610_2 these findings reveal that the mir-126 direct targetgenes igfbp2, pitpnc1 and mertk are individually required for endothelial recruitment and metastatic colonization, are downstream of mir-126 and individually correlate in expression with human metastatic progression. 22476949_1 mir-181a targets the 3- untranslated region of sirt1 mrna through a mir-181a binding site, and down-regulates sirt1 protein abundance at the translational level. 22476949_2 mir-181a regulates sirt1 and improves hepatic insulin sensitivity. 22476949_3 these data demonstrate that mir-181a targets sirt1 3'-utr through its binding site within sirt1 3'-utr. 10903453_1 the second gene, c6uas, is transcribed in the antisense orientation from the complementary strand of c6orf4-6. 10903453_3 c6uas has no apparent orf and most likely represents a structural rna gene that is transcribed but not translated. 10903453_4 this feature and the antisense polarity of transcription suggest that c6uas could play a regulatory role on the expression of c6orf4, as indicated by a significant decrease of endogenous c6orf4 expression after transfection of c6uas cdna in human fibroblasts. 10903453_5 neither c6uas nor c6orf4-6 genes show any homology with known human genes. 21706480_1 furthermore, caspase-3 is identified as a novel target of mir-155. 21706480_3 figure 2. mir-155 can inhibit fadd and caspase-3 via targeting the 3'-utrs of fadd and caspase-3. 21706480_4 together, these results confirmed that mir-155 expressed in human np and mir-155 down-regulated fadd and caspase-3. 25897432_1 mir-31 suppressed the luciferase activity in reporter construct containing the stmn1 3- -untranslated region , confirming that mir-31 directly targets stmn1. 25897432_2 these results indicate that mir-31 directly suppressed stmn1 expression via sequence-specific interactions with 3'-utr of stmn1. in the current study, we first demonstrated that mir-31 directly represses expression of stmn1, induces microtubule polymerization, where the microtubules were bundled nearby the boundary of the cell, and subsequently modulates the sensitivity of a cell towards tx. 20574151_1 we then demonstrate that mir-520b and mir-520e are able to directly targetthe 3'untranslated regions of the membrane-bound complement regulatory protein cd46; suggesting that mir-520b and mir-520e down-regulate cd46 at post-transcriptional level. 20574151_2 thus, we conclude that mir-520b is able to downregulate the expression of cd46 at the post-transcriptional level. 20574151_3 these data elucidate that mir-520b and mir-520e can directly targetthe cd46 gene by binding to the 3'utr, which further supports that mir-520b is able to downregulate the expression of cd46 at post-transcriptional level. 17914404_1 several recent studies have found a conserved microrna family, the mir-34s, to be direct transcriptional target of p53. 17914404_2 mir-34 activation can recapitulate elements of p53 activity, including induction of cell-cycle arrest and promotion of apoptosis, and loss of mir-34 can impair p53-mediated cell death. 23479506_1 besides others, this was exemplified for abundant asml wt-exosomal mir-494 and mir-542-3p, which target cadherin-17 . 23479506_2 furthermore,a 3'-utr mal and cdh17 luciferase reporter assay confirmed that mal and cdh17 are targeted by mir-494 and cdh17 by mir-542-3p. 23479506_3 we focused on abundant mir-494, potentially targeting mal and cdh17, and mir-542-3p, targeting cdh17 and traf4. 23479506_4 qrt-pcr revealed down-regulation of mal and cdh17 by mir-494, of cdh17 and traf4 by mir-542-3p, of traf4 by mir-290, and of klf4 by mir-204 and mir-26b. 25196583_1 together,these results show that gas5 contributes to the pathogenesis of oa by acting as a negative regulator of mir-21 and thereby regulating cell survival. 25652145_1 the results showed that mir-362-3p significantly reduced the expression of cd82 in gc cells compared with the control cells. 25652145_2 these data suggested that cd82 is directly regulated by mir-362-3p. 25652145_3 the results suggested that mir-362-3p functions synergistically with cd82 to inhibit gc cell migration and invasion activities . 26459935_1 apaf1 and casp7 are target genes of mir-19b. 26459935_2 the 3'-utrs of apaf1 and casp7 mrna have binding sites for mir-19b. in conclusion, these results demonstrated that both afap1 and casp7 are target genes of mir-19b. 22330340_2 significant repression of luciferase activity was observed after co-transfection of pax3-3'-utr with mir-1 and/or -206 precursors compared with scrambled controls, which suggests that mir-1 and -206 can targetpax3. 22330340_3 figure 3 mir-1 and -206 regulates pax3 expression through sequence-specific binding to its 3'-utr. 22330340_4 these results indicate that both binding sites of mir-1 and -206 in pax3 are functional and there is minimal preference between these binding sites. 22330340_5 these data also suggests that there was no preferential selection between mir-1 and -206 to regulate pax3 at least under the current experimental conditions. 21518763_1 the negative regulation of mir-365 was strictly dependent on a microrna binding element in the 3'-utr of il-6 mrna. 21518763_3 1a, only transfection with mir-365 expression vector significantly down-regulated luciferase activity compared with transfection with an empty vector, indicating that mir-365 is a potential regulator of il-6. 21518763_4 thus, it can be concluded that mir-365 decreases il-6 expression by repressing its mrna translation but does not affect its mrna stability. 21518763_5 these results provided experimental support to the prediction that the mir-365 response element is located in the 3'-utr of il-6. 19615744_1 the mrna expression of transcription factor myb, the designated target of mir-150, was shown to correlate inversely with the mir-150 level. 19615744_2 however, by comparing mirna and mrna levels, it became apparent that, in mds, mir-150/myb transcripts and mir-222/p27 transcripts showed a significant inverse correlation . 22525256_2 mir-126 overexpression significantly downregulated spred-1 in epcs. 20388878_1 met and foxo3 as target of mir-206 and mir-221-222. 20388878_2 we identified hepatocyte growth factor receptor and forkhead box o3 as new target of mir-206 and mir-221-222, respectively. 20388878_3 western blot analyses confirmed that mir-206-expressing cells repressed the expression of met but activated that of foxo3, cdkn1b, and bim. 20388878_4 met and foxo3, previously found to be repressed at the mrna and protein levels by mir-206 and mir-221-222, respectively , were also found in our list of underexpressed target. 20388878_5 we concluded that mir-206 target met and that mir-221 and -222 targetfoxo3 by binding sites within the 3'-utrs. 20162574_1 bcl2 is a targetgene of the mature mir-181s. 20162574_2 the luciferase activity of a bcl2 3'-untranslated region-based reporter construct in sgc7901/vcr and a549/cddp cells suggests that a new targetsite in the 3'-utr of bcl2 of the mature mir-181s was found. in sgc7901/vcr and a549/cddp cells, a significant decrease in relative luciferase activity was noted when pgl3-bcl2-3'-utr was cotransfected with the mature mir-181s mimic but not with the control mirna mimic, respectively , which suggests that the position 2888-2894 of bcl2 3'-utr is also a targetsite by the mature mir-181s. 20162574_3 as bcl2 is an antiapoptotic protein and a target of the mature mir-181s, we hypothesized that the mir-181b might modulate mdr of cancer cells by repressing the bcl2 protein expression. 20162574_4 these results demonstrated that mir-181b may modulate mdr of cancer cell lines, at least in part, by repressing the bcl2 protein expression. 25968989_1 in both studies mir-28-3p negatively correlated with cyp2c9 mrna, whereas mir-148b-3p was negatively correlated with cyp2c9 mrna in our study. 21381024_1 over-expression of mir-21 decreased both protein and mrna levels of stat3, whereas inhibiting mir-21 with 2'-o-methyl-antisense rna increased these levels. 21381024_2 fig. 4. mir-21 target the 3'utr of stat3 mrna. 21381024_3 real-time pcr and western blot analyses showed that mir-21-overexpressing hscs exhibited less total and phospho-stat3 expression and that anti-mir-21-transfected hscs exhibited increased stat3 expression . 26876166_2 thus, the observed change in a2bp1 protein abundance by altering mir-980 levels, the improvement of memory with mir-980 inhibition and a2bp1 overexpression, and results from epistasis experiments are consistent with the model that the normal memory suppressing effects of mir-980 occur through its regulation of the memory-promoting gene, a2bp1. 26876166_3 our behavioral, molecular, cellular, and genetic data together argue that a2bp1 is a primary target of mir-980 for memory suppression. 26792405_1 cnot6 identified as the target gene of mir-29c-3p 26759236_1 mir-125a targeted fih1 and irf4 to enhance m1 and attenuate m2 polarization simultaneously .the 26759236_2 3'-utrs of fih1 and irf4 are potential mir-125a targets. 26759236_3 these data suggested that mir-125a downregulated fih1 and irf4 in macrophages through their 3'-utrs. 22078727_1 in the present study, we showed that mir-449a/b regulates hdac1 by directly binding with the 3' untranslated region of the hdac1. 22078727_2 this result suggests that mir-449a and mir-449b repress hdac1 transcription by direct binding to the 3'-utr. 22078727_3 conversely, anti-mir-449a/b induced up-regulation of the hdac1 expression in hcc1436 cells . in this study, mir-449a/b had lower expression and hdac1 was over-expressed in lung cancer. 22078727_4 we observed substantial hdac1 suppression by mir-449a/b at the mrna and protein levels in lung cancer. 22078727_6 our findings indicated that the down-regulation of mir-449a/b resulted in an up-regulation of hdac1 in primary lung cancer. 22078727_7 moreover, hdac1 was directly regulated by mir-449a/b through binding of the 3'-utr. 26787543_1 it has been reported that inhibition of let-7d caused emt in mice by targeting hmga2. 26787543_2 let-7d has anti-fibrotic effects in pulmonary fibrosis and hmga2 is one of the targets of let-7d. 25564423_1 these results suggested that mir-132 strongly targets foxo3. 25564423_2 since foxo3 plays a role in the inhibition of cell cycle progression and inflammatory cytokine progression, we analyzed levels of ifn--gamma, ccnd1 and ccne1 after transfection with mir-132 mimic and inhibitor. 25564423_3 we observed that the overexpression of mir -132 corresponded positively with the expression of ifn--gamma, ccnd1 and ccne1 , while its inhibition, decreased their levels significantly suggesting that targeting of foxo3 by mir-132 prevents regulation of inflammatory cytokine production and cell cycle progression. 20972335_2 therefore, we investigated whether mir-424 could decrease the levels of cul2 transcripts. 20972335_3 these results suggest that mir-424 reduces cul2 levels largely by translational inhibition. 20972335_4 from these data we concluded that mir-424 stabilizes hif-1alpha by targeting cul2 and thus indirectly destabilizing the components of vcbcr complex. 22995304_2 then, to examine whether mir-486 actually downregulates the five genes or not, we performed real-time pcr analysis of rna samples from 2645/94 cells transfected with mir-486 or control oligo, and only pai-1 mrna level was confirmed to be decreased by exogenous mir-486 expression . 22325466_1 these results indicate that mir-182 target the creb1 gene and suppresses gastric adenocarcinoma cell growth, suggesting that mir-182 shows tumor-suppressive activity in human gastric cancer. 22325466_2 in contrast, egfp expression levels with the mutated creb1 3'-utr were not influenced by alteration of mir-182 . 22325466_3 these data indicated that mir-182 could bindto the specific sites of the creb1 mrna 3'-utr and negatively regulate the expression of the creb1 gene. in addition, we found that the expression level of creb1 mrna in gastric adenocarcinoma tissues was significantly higher than that in matching adjacent, normal tissues in the 10 pairs of gastric tissues . 22325466_4 all of these data indicate that mir-182 negatively regulates the expression of creb1. 22325466_6 altogether, creb1, as an oncogene, is a direct target of mir-182 and a mediator of mir-182 function in gastric cancer cells. in summary, we have demonstrated that mir-182 expression is downregulated in gastric adenocarcinoma tissues, and that mir-182 inhibits gastric adenocarcinomacell viability and colony formation by targeting creb1. 26535064_1 our results indicate that mir-222 controls capan-2 cell proliferation by targeting p57. 26535064_2 as p27 and p57 have been reported as putative target genes of mir-222 in other types of cancer cells 23, 24, we assessed the effects of mir-222 in endogenous expressions of p27 and p57 in capan-2 cells by western blotting, finding that the protein level of p57 but not p27 was endogenously regulated by mir-222 mimic and inhibitor . 26535064_3 furthermore, pten, another well-known target of mir-222, was not modified by mir-222 in capan-2 cells . 26535064_4 the results indicate that p57 is a target gene of mir-222 in capan-2 cells. 26535064_5 the edu results showed that the proliferation-suppressing effects of mir-222 inhibitor in capan-2 cells could be partially reversed by silencing p57 ,4b, indicating that mir-222 promoted capan-2 cell proliferation, at least in part, via p57 targeting. 25444916_1 taken together, this study highlights that the proapoptotic effects of curcumin depend on mir-192-5p/215 induction and the p53-mir-192-5p/215-xiap pathway is an important therapeutic target for non-small cell lung cancer. 26003727_1 mmp9 is a direct target of mir-204 in bewo cells. 26003727_2 t mmp9 could be directly targeted by mir-204 in human trophoblast-like cells. 25545945_1 which suggests that mir-181c inhibits hypoxia-induced tlr4 expression in primary microglial cells. 25545945_2 these results indicate that mir-181c likely suppresses tlr4 expression by directly binding target sites in the tlr4 3'-utr. 26424132_1 the target genes were predicted, and we used a dual-luciferase reporter assay to demonstrate that mir-1and mir-206 directlytargeted the 3'-untranslated region of paired-box transcription factor pax7 and histone deacetylase 4 . 26424132_2 our results suggests that mir-1 and mir-206 promote bovine skeletal muscle satellite cell myogenic differentiation and restrict their proliferative potential by regulating pax7 and histone deacetylase 4 expression. 26424132_3 our results showed that renilla luciferase activity was downregulated significantly when pax7-3'-utr or hdac4-3'-utr were cloned into the psicheck-2 vector, which suggested that pax7 and hdac4 are direct targets of mir-1 and mir-206 . 26424132_4 these results indicated that mir-1 and mir-206 post-transcriptionally inhibited pax7 and hdac4 translation by targeting the 3 utr of pax7 or hdac4 mrna in bovine skeletal muscle satellite cells. 21763238_1 the overexpressed mir-122a bound to a binding motif at the 3'-untranslated region of occludin messenger rna to induce its degradation; mrna degradation depleted occludin from enterocytes, resulting in increased intestinal tj permeability. 21763238_2 the deletion of the mir-122a binding sequence on 3'-utr prevented the pre-mir-122a inhibition of luciferase activity , suggesting that mir-122a inhibits the luciferase activity by binding to its complementary sequence on 3'-utr. 21763238_3 these results indicated that the increase in mir-122a expression was required for the tnf-alpha induced degradation of occludin mrna and increase in caco-2 tj permeability. 21763238_4 these in-vivo studies indicated that the tnf-alpha induced increase in intestinal permeability was associated with an increase in enterocyte mir-122a expression and a decrease in occludin level. 23478189_1 akt2 was verified to be one of the direct targets of mir-612, through which the epithelial-搈esenchymal transition and metastasis were inhibited. 23478189_2 this finding suggested that akt2 is a key target of mir-612. in other words, akt2 is a functional target gene of mir-612. 23478189_3 thus, we conclude that akt2 is a direct target gene of mir-612. 25660220_1 mir-144 inhibits proliferation and induces apoptosis and autophagy in lung cancer cells by targeting tigar. 26056009_1 hence, in this study, the differentiated macrophages were initially transfected with mir-29a or its inhibitor and it was shown that qki is a direct target of mir-29a. 26056009_2 moreover, with the help of luciferase reporter vector, it was shown that qki inhibited sra transcription by binding to qre region in its 3 ' utr mrna. 26056009_3 this suggests that mir-29a promotes the formation of qki mrna with ago2 and regulates qki post-transcriptionally. 26507842_1 combining bioinformatics prediction and biochemical analyses, we showed that adam9 and ros1 are direct downstream targets of mir-33a. 26507842_2 taken together, these results indicate that adam9 and ros1 are direct targets of mir-33a in breast cancer cells. 26507842_3 moreover, the mir-33a level is inversely associated with the expression of adam9 and ros1 in breast cancer tissues, indicating that mir-33a may inhibit breast cancer cell proliferation and metastasis, at least in part, by downregulating the levels of adam9 and ros1. 20185821_1 mir-34a decreased sirt1 levels by binding to the 3'-untranslated region of sirt1 mrna. 20185821_2 our study demonstrates an unexpected role of the fxr/shp pathway in controlling sirt1 levels via mir-34a inhibition and that elevated mir-34a levels in obese mice contribute to decreased sirt1 levels. 20185821_3 figure 3. sirt1 is a target of mir-34a in hepatocytes. 20185821_4 these results confirm the previous findings that sirt1 is a target of mir-34a and show that this inhibition occurs in hepatic cells. 20185821_5 consistent with the hepg2 cell studies, overexpression of mir-34a in mouseliver significantly decreased sirt1 protein levels . 20185821_6 these results demonstrate that sirt1 is a target of mir-34a in mouseliver in vivo. 23209550_1 in addition, mir-142-5p and mir-155 suppress the proapoptotic gene tp53inp1 as their target. 23209550_3 4a, -榮eed' matches between the 5'-end of the mirnas and the 3'-utr of tp53inp1 were stronger in mir-155 than in mir-142, suggesting that mir-155 may have a more profound effect on suppression of tp53inp1. 23209550_4 these findings suggest that tp53inp1 is a common target of mir-142-5p and mir-155 and is suppressed by overexpression of both mir-142-5p and mir-155 in gastric malt lymphoma lesions. 22326846_1 down-regulation of mir-1 was associated with up-regulation of its predicted target sorcin, an established modulator of calcium signaling and excitation-contraction coupling, subsequently verified as a mir-1 target with luciferase constructs. 22326846_3 4.identification of a sri as a mir-1 target. 22326846_4 a, predicted pairing of mir-1 and sri in mouse and human . 22326846_5 there was reciprocal down-regulation of sri protein levels with mir-1 mimic and sri up-regulation with mir-1 inhibitor . 22326846_6 together, the data verified sri as a regulatory target of mir-1. 22665054_1 we now report that stmn1 is upregulated during the progression of melanoma relative to benign nevi, and that stmn1 is directly regulated by mir-193b. 22665054_2 the use of a luciferase reporter assay confirmed that mir-193b directly regulates stmn1 by targeting the 3'-untranslated region of stmn1 mrna. 22665054_3 these results suggest that mir-193b post-transcriptionally regulates stmn1 expression through direct interaction with the predicted seed-binding site. 20850013_1 nevertheless, a highly conserved sequence with partial complementary to mir-146a was present in the mouse stat1 3'-utr . 20850013_2 although computational algorithms relying on mirna seed sequence analysis failed to identify mouse stat1 as a mir-146a putative target, it was recently shown that some micrornas, like mir-24, control multiple genes in the absence of canonical target seed sequences . 20850013_3 together, these results suggested mouse stat1 serves as a target of mir-146a in mouse t cells . 20850013_4 levels of phosphorylated stat1 were also markedly increased in mir-146a-deficient cells. 20850013_5 together, these results provided genetic evidence that mir-146a ensures treg cell-mediated control of th1 responses at least in part through targeting stat1 and that limiting stat1 expression in mir-146a-deficient treg cells moderates these responses. 19773441_1 transfection of mir-34a also reduced the protein levels of notch-1, notch-2, and cdk6 in glioma cells and stem cells . 19773441_2 together, these data show that mir-34a binds c-met 3'-utr, notch-1 3'-utr, and notch-2 3'-utr and down-regulates c-met, notch-1, notch-2, and cdk6 protein expressions. 19773441_3 mir-34a expression reduced c-met mrna levels, albeit less than it reduced protein levels . 19773441_4 this suggests that mir-34a affects both c-met transcription and c-met mrna degradation. 26638007_1 these findings support the hypothesis that tgif2 is a direct target gene for mir-148a in skin cancer cells. in addition, tgif2 was thought to be a target gene of mir-148a. 26638007_2 our findings indicated that dna methylation-associated down-regulation of mir-148a could contribute to the metastasis of skin cancer by targeting with tgif2 gene. 26638007_3 the expression of mir-148a is decreased in patients with skin cancer by targeting with tgif2. 26654953_1 based on bioinformatics analysis and luciferase reporter assay, we transfected mir-486 mimic and mir-486 inhibitor into thp-1 macrophage-derived foam cells, and found that mir-486 directly bound to histone acetyltransferase-1 3'-utr, and downregulated its mrna and protein expression. 26654953_2 based on these findings, we hypothesized that mir-486 promotes cholesterol accumulation in macrophages by targeting hat1. 26654953_3 meanwhile, the luciferase reporter assays in thp-1 macrophages confirmed that hat1, but not abca1, was a direct target of mir-486 . 26654953_4 these results suggested that mir-486 might have a regulatory effect on the post-transcriptional regulation of hat1 expression via targeting 3'-utr of hat1. 26498529_1 we showed that mir-374b specifically bound to the 3'untranslated region of myf6 and down-regulated the expression of myf6 gene at both mrna and protein level. 26498529_3 these results illustrated that mir-374b specially binds to the putative site of myf6 3' utr. 26498529_4 these results indicated mir-374b could regulate endogenous myf6 expression at both mrna and protein level. 26376209_2 suggesting that these cytokines and chemokines induced by il-17 stimulation were not directly targeted by mir-30a. 26376209_3 these data indicate that mir-30a can suppress act1 expression by degradation of its mrna or inhibition of its translation. 26376209_4 these data indicate that mir-30a-mediated inhibition of il-17-mediated inflammation was mainly caused by its suppression of act1 expression. 20103677_5 moreover, transfection with precursors to mir-193b decreased both mcl-1 expression and the ic50 to sorafenib. 26559013_1 together, these results indicated that pik3ca was a direct target of mir- 490- 5p in achn cells. 22773844_1 in the present study, we obtained evidence indicating that mir-196a specifically binds the 3'-utr region of anxa1 mrna to repress its expression. in the present study, we show that anxa1 is post-transcriptionally regulated by mir-196a in response to vegf, which contributes to regulate endothelial cell migration. 22773844_2 this indicated that mir-196a inhibited cell migration by targeting anxa1. 22773844_3 these finding are consistent with the fact that the regulation of mir-196a by regulating the level of anxa1 may be importantly involved in maintaining endothelial cells in a quiescent state in non-activated conditions. 25515961_1 inhibition of mir-486-5p reduced cml progenitor growth and enhanced apoptosis following imatinib treatment.the 25515961_2 effects of mir-486-5p on hematopoietic cell growth and survival are mediated at least in part via regulation of akt signaling and foxo1 expression. 19543271_1 these results confirm that pten 3'-utr is a target of mir-216a and mir-217. in summary, mir-216a and mir-217 are co-expressed with rp23 and downregulate the same target , illustrating an efficient way to control targetgenes under certain disease states . 19543271_2 our current results also demonstrate a new mechanism for akt activation by tgf--beta via pten downregulation by mir-216a/217, and controlled by upstream mir-192 . 26497032_1 these results suggested that bace1 might be a direct target of mir-425-5p and mir-339-5p. 26497032_2 mir-425-5p and mir-339-5p regulate bace1 protein levels in n2a/appswe cells. 26521941_1 we found that mir-185 directly targets the 3- -untranslated region of na + /h + exchanger-1 , a protein involved in ers. in the present study, we determined that mir-185 inhibits the expression of nhe-1 by direct binding to two recognition sites within the 3'-utr and the inhibition could lead to alleviation of ers-induced myocardial apoptosis. 26521941_2 taken together, these data suggest that mir-185 negatively regulates nhe-1 expression both at the mrna and protein levels and that the negative effect is mediated by direct binding of mir-185 to the 3'-utr of nhe-1 mrna. 26521941_3 mir-185 directly targets two distinct sites in the 3'-utr of nhe-1, thereby inhibiting nhe-1 expression. 26320367_1 on the other hand, overexpression of mir-381 mimics reduced lrh-1 expression in both cells , suggesting that lrh-1 was the target of mir-381. 26320367_2 at the molecular level, our results revealed that lrh-1 was a direct target of mir-381 in colon cancer cells. 26320367_3 mir-381 directly targets the lrh-1 in colon cancer cells. 25960234_1 the mir-133a increased the expression of phosphorylated akt in the heart of chf rats . 25960234_2 he mir-133a increased the expression of phosphorylated akt in the heart of chronic heart failure rats. 23395168_1 analysis of the network suggested that prdm16 is repressed by the satellite cell-enriched mir-133a and mir-133b. 23395168_2 we identified a highly conserved target site for mir-133a and mir-133b with an absolutely conserved 8 nt seed sequence in the 3'utr of prdm16 mrna . 23395168_4 these data indicate that mir-133 regulates brown adipose determination in primary brown preadipocytes by targeting prdm16. 23395168_5 taken together, these data support the hypothesis that mir-133 expression enforces myogenic commitment of satellite cells by targeting prdm16 expression and repressing brown adipogenic determination. 26807182_1 luciferase assays revealed that mir-125b directly targeted the 3'-utr of sphk1. 26807182_2 collectively, our results demonstrated that sphk1 is a direct target of mir-125b in bladder cancer cells. 26324025_1 the specific-strand rt-qpcr and western blotting results showed that sirt1-as overexpression did not influence sirt1 mrna expression, but markedly elevated the sirt1 protein level . 26324025_2 the results suggested that sirt1-as functioned positively in the regulation of sirt1 expression at the post-transcriptional level. 26567912_1 we successfully overexpressed mir-containing plasmids in mcf7 and mda-mb-231 cells as shown by an increase in gene expression of mir-203, -887 and -3619 and mir-182 in transfected cells compared to non-transfected cells. 23166356_1 the direct repression of irf8 and myb by mir-155 was demonstrated in an analogous assay . 22174856_2 6c, nedd4 and fgd1 each contain a putative binding site for the microrna-200 family members including microrna-200c. 22174856_4 targetscan alignment of microrna-200c binding site at 3'-utr of two computationally prioritized microrna-200c putative targets nedd4 and fgd1. 23558936_1 furthermore, mir-21 mimic or inhibitor significantly reduced or increased the expression of pdcd4 and tpm1. 26464662_1 furthermore, a tumor suppressor gene, tissue inhibitor of metallopeptidases-2 was identified as a direct target of mir-301a and knockdown of timp2 could mimic the effect of mir-301a in mm. 26464662_2 furthermore, the results of western blot indicated that mir-301a overexpression suppressed timp2 expression while mir-301a inhibition promoted timp2 expression . 26464662_3 these results indicate that the effect of mir-301a on mm cells is involved in its suppression of timp2. 26066330_1 mir-137 down-regulates the src3 gene through interaction with its 3'-utr. 26066330_2 these data support the presence of 3 functional mrss within the src3 3'-utr that can bind mir-137 and explain why mir-137 can so potently deplete src3 expression in all experimental models that we have tested. 26066330_3 mir-137 directly binds to the src3 3'-utr. 26823724_1 overlap analysis between mir-195 target genes and angiogenesis genes was performed, as shown in figure 3a, fgf2 and vegfa were identified. 26823724_2 these results indicating that mir-195 may participate in lung metastases of hcc by regulating fgf2 and vegfa. 26823724_3 results revealed that mir-195 mimics significantly suppressed the luciferase activity of fgf2 wt-utr. 26823724_4 the results showed that mir-195 overexpression markedly inhibited endogenous expression of fgf2 and vegfa protein . 23948100_1 mir-34a directly inhibits bcl2 and xiap, both anti-apoptotic proteins. 21856783_1 mir-365 inhibits both endogenous hdac4 protein levels as well as the activity of a reporter gene bearing the 3'-untranslated region of hdac4 mrna. 21856783_2 expression of mir-365 mimic significantly inhibited hdac4 protein levels in both chicken and mouse chondrocytes . 21856783_3 conversely, expression of a mir-365 inhibitor stimulated the endogenous levels of hdac4 protein in chondrocytes . 21856783_4 to identify the mir-365 targetregion in the hdac4 mrna, we mutated 3 nucleotides from the putative seed region in the hdac4 3'-utr . 21856783_5 while transfection of mir-365 mimic suppressed the luciferase activity of the wild-type hdac4 3'-utr reporter, this suppression was abolished in the mutated hdac4 3'-utr reporter . 21856783_6 overexpression of hdac4 could reverse the induction of chondrocyte differentiation by mir-365, thus providing evidence that mir-365 mediates the induction of chondrocyte differentiation via targeting hdac4 . 22240259_1 but the results of luciferase targeting assay in hek 293t cells and the overexpression of mir-200a in ratnrk cells demonstratd that mir-200a did targetrat-beta-catenin mrna and cause the suppression of its expression. 22240259_2 the result suggests that rat-beta-catenin might also be a targetgene of mir-200a and the increase of mir-200a causes the down-regulation of -beta-catenin mrna. 22240259_3 this result indicates that mir-200a directly target rat-beta-catenin mrna by binding the targetsite. 22240259_4 the expression of the endogenous -beta-catenin protein with overexpression of mir-200a is detected further in ratnrk cells. 22240259_5 figure 6 shows that mir-200a inhibits significantly the endogenous expression of -beta-catenin protein in ratnrk cells transfected by mir-200a mimics. 22240259_6 all results validate that rat-beta-catenin mrna is also a targetgene of mir-200a. 23818290_1 we also identified nuclear respiratory factor-1 , a critical regulator of the mitochondrial function, as a direct target of mir-378. 23818290_2 fisetin suppresses the aberrant expression of hepatic mir-378, a mir located in intron of the peroxisome proliferator-activated receptor gamma coactivator-1beta ,which targets the nrf-1involved in mitochondrial function. 24039836_1 luciferase reporter assay demonstrated that mir-151-5p can bind to the 3'-utr of fxyd1 and inhibit its expression.estrogen 24039836_2 deficiency exacerbates mi-induced upregulation of plm expression via down-regulating mir-151-5p. 26674378_1 furthermore, we revealed the mechanism that mir-425 inhibited the expression of smad2 by targeting the second binding site in the 3'-untranslated region in escc. 26674378_2 taken together, our results show that mir-425 functions as an oncogene by targeting the 3'-utr of smad2 and indicate the potential utility of plasma mir-425 as a novel biomarker for escc diagnosis. 26674378_3 fig. 4. mir-425 regulated the expression of smad2 by targeting the 3' -utr. 26315535_1 the targetscan prediction software identified 2 and 3 putative binding sites for mir-9-5p in the 30 untranslated regions of the tgfbr2 and nox4 mrna. 26315535_2 this prediction was functionally validated by over-expressing mir-9-5p in pulmonary fibroblasts , which resulted in a decrease of tgfbr2 mrna and protein levels and also reduced the mrna and protein expression of nox4 after induction by tgf-b1 . 26315535_3 the data are consistent with a direct regulation of tgfbr2 and nox4 by mir-9-5p. 25231457_1 previously, it has been shown that stat5 is a direct activator of mir-182 which is in turn a robust inhibitor of foxo1. 25231457_3 thus, under oxidative stress and mir-182 down-regulation, foxo1 has the opportunity to be translated leading to foxo1 over-expression. 25231457_4 finally, pro-apoptotic gene targets of foxo1 e.g., bim and bax are up-regulated leading to apoptosis. 24728149_1 mir-34a plays a role in regulation of ang ii-induced cardiomyocyte hypertrophy by inhibition of atg9a expression and autophagic activity. 20406979_1 knockdown of p21 in mll-transformed cells phenocopied the overexpression of the mir-17 polycistron, including a significant decrease in leukemia latency,validating p21 as a biologically relevant and direct in vivo target of the mir-17 polycistron in mll leukemia. 20406979_2 because the seed regions of mir-17-5p and mir-20a share perfect complementarities with the 3- utr of p21 mrna , this suggested that these micrornas may directly regulate p21 to modulate cell cycle progression in mll leukemia cells. 20406979_3 thus, p21 is a critical in vivo and direct target of the mir-17 polycistron in mediating mll leukemias. 24885920_2 ectopic expression of mir-139-5p in colon cancer cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay and in xenograft tumor growth in nude mice . 24885920_3 mir-139-5p induced apoptosis , concomitantly with up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3, caspase-7 and parp. 26824500_1 previous report indicated that the plk1 was a target of mir-100 . 26824500_2 immunoblot analysis showed that the expression level of plk1 was indeed up-regulated and down-regulated in huh7 cells upon silencing and overexpressing mir-100. 26824500_3 this result indicated that the physical interaction between prec-pol and mir-100 resulted in an inhibitory effect on the mir-100 function, leading to plk1 up-regulation. 26824500_5 furthermore, among the 115 patients, pearson's correlation analysis revealed a negative correlation between mir-100 and plk1. 24686458_1 here, we report that microrna 376a regulates primordial follicle assembly by modulating the expression of proliferating cell nuclear antigen , a gene we previously reported to regulate primordial follicle assembly by regulating oocyte apoptosis in mouse ovaries. 24686458_2 mir-376a was shown to be negatively correlated with pcna mrna expression in fetal and neonatal mouse ovaries and to directly bind to pcna mrna 3' untranslated region. 26819305_3 fig 3 eef1a1 is a target of mir-33a-5p. 26819305_5 8, cotransfection of mir-33a-5p mimics and vector markedly reduced jev replication, whereas cotransfection of mir-33a-5p mimics and myc-tagged eef1a1 plasmid countervailed the inhibition, indicating that mir-33a-5p negatively regulates jev replication by targeting eef1a1. 21880628_1 a significant reduction was also apparent for the newly identified mirna-target gene pairs clcn3-mir-15a, crkl-mir-15a, irf2-mir-20a, kit-mir-19a and -mir-20a, mn1-mir-15a as well as serpinb9-mir-29a . 26429314_1 forcing mir-29a caused a downregulation of the cytotoxicity determinant nk activating receptor via upregulation of mir-155. 26429314_2 using luciferase reporter assay, it was proven that mir-155 binds to the 3 ' utr of nkg2d mrna and hence alters its expression . 26429314_3 this study concludes that mir-29a alters the expression of the transcription factor pu.1, which in turn manipulates the expression of mir-155 and its downstream target activating receptor nkg2d as well as the cytolytic effector prf-1 and hence causes a reduction in cytolytic effect of nk cells on hcv infected cell models . 26232986_1 in addition, protein kinase c alpha was also identified as a direct target of mir-150-5p by establishing a mirna-mrna network, and this target was validated via dual-luciferase reporter and western blot analysis. 26232986_2 taken together, these results supported that prkca is a direct target gene of mir-150-5p. 26238950_2 the above data identified that stat3 is a direct target gene of mir-519d. 26238950_3 this study also shows that mir-519d plays an important role in the regulation of breast cancer cell proliferation and invasion by downregulating stat3. 22764048_1 we further demonstrate that pax6 is an important target of mir-7. in this study, we characterized mir-7 expression and identified its functions in endocrine cell differentiation. 22764048_2 we show that mir-7 directly represses pax6 mrna expression and fine-tunes its levels. 22764048_3 pax6 is a mir-7 target taken together, these results indicate that pax6 is a bona fide target of mir-7 in -beta-cells. 22764048_5 accordingly, mir-7 kd resulted in reduced numbers of ghrelin-positive cells , supporting the view that mir-7 knockdown acts upstream of pax6 to promote differentiation into insulin- and glucagon-positive cells at the expense of ghrelin-positive cells. 22764048_6 thus, gain-of-function analysis substantiates our conclusions that mir-7 regulates pax6 and downstream endocrine genes, including insulin and ghrelin. 22764048_7 therefore, when mir-7 was overexpressed in pdx1-cre;rosa26-mir-7 embryos, pax6 levels decreased and the expression of insulin and glucagon was downregulated, providing in vivo evidence for control of pax6 by mir-7. 26240284_1 in hdac10 knockdown cells, let-7f and microrna 98 were upregulated and the let-7 family target, hmga2, was downregulated. 26240284_2 many let-7 family members were highly expressed in hdac10 knockdown cells and reduced in cells overexpressing hdac10 . 26240284_3 using the same reporter system, hdac10 only regulated the wt hmga2 3'-utr, but not the mutant , which indicated that the effect of hdac10 on the hmga2 3'-utr required some or all of the seven conserved let-7 sites. 26240284_4 we concluded that hdac10 regulates the hmga2 3'-utr through let-7 family members. 22395361_1 mir-30a is a potent inhibitor of autophagy by downregulating beclin 1 and atg5 expression. 22018986_1 we then performed a luciferase reporter assay to verify that let-7a directly target nirf. 22018986_2 these results suggest that the 3'-utr of the nirf gene contained regulatory elements by which let-7a regulates nirf expression. 22018986_3 taken together, these data indicate that let-7a may regulate nirf expression through let-7a-binding sites at the 3' -utr of nirf. 22018986_4 moreover, a significant negative correlation between let-7a and nirf mrna and protein levels was revealed in both crc tissues and colon cancer cells . 22018986_5 this observation is in accordance with our previous observations that let-7a suppressed the expression of nirf. in addition, our results show that let-7a negatively regulates nirf expression and inhibits crc tumorigenesis in nude mice. 23223022_1 western blot analysis showed increases in the levels of p70s6k, eif4e, mknk1, mknk2, and mapkap1, as well as in the phosphorylation of s6 and eif4e in mir-7a-deficient mouse islets demonstrated that suppression of mir-7a activated mtor signaling in primary islets. 23568547_1 also, caspase-2 was proved to be one of direct targets of mir-708 in t24 and 5637 cells. 23568547_2 moreover, we found that caspase-2 was a direct target of mir-708. 23568547_3 these results suggested that this site in the 3' utr of caspase-2 mrna was the direct interaction site with mir-708. in bladder carcinoma cell line t24 and 5637, using luciferase assay and western blotting assay, we found a direct link between mir-708 and its putative target caspase-2, which has been extensively verified to be an apoptosis inducer. 23137536_1 mir-186, mir-216b, mir-337-3p, and mir-760 cooperatively induce cellular senescence by targeting a subunit of protein kinase ckii in human colorectal cancer cells. 23137536_2 as a result, we found that mir-186, mir-216b, mir- 337-3p, and mir-760 could target the 3' utr of ckiialpha mrna . 23137536_3 taken together, these results indicate that mir-186, mir-216b, mir-337-3p, and mir-760 jointly function to repress ckiialpha expression by reducing the stability of ckiialpha mrna through specific targeting of the 3' utr of ckiialpha mrna in hct116 cells. 23137536_4 taken together, these results suggest that mir-186, mir-216b, mir-337-3p, and mir-760 may induce senescence through ckii inhibition-mediated ros generation. 23137536_5 taken together, these results indicate that ckii inhibition-mediated senescence can be blocked by antisense inhibitors of mir-186, mir-216b, mir-337-3p, and mir-760 in hct116 cells. 23137536_6 taken together, these results strongly indicate that mir-186, mir-216b, mir-337-3p, and mir-760 jointly produce ros and induce senescence through ckiialpha downregulation. 26318398_1 fig. 4b shows the effect of mir-27a knockdown and overexpression on the levels of ldlr mrna and protein. 26318398_2 we concluded that mir-27a induced a decrease in ldlr at mrna and protein levels. 26660116_1 furthermore, overexpression of mir-9 inhibits the expression of bcl2l11 protein while inhibition of mir-9 enhances the expression of bcl2l11 proteins in primary cultures . 26660116_2 finally, as mir-9 is upregulated in mcao mice and ogd neurons, we examined the protein level of bcl2l11 in those conditions and found that bcl2l11 proteins are increased significantly in both mcao mice and ogd neurons . 26572153_2 further, we identified tumor suppressor foxo1 was a novel target of mir-411 in the lung cancer cells and knockdown of foxo1 in lung cancer cells in which mir-411 was inhibited could enhance cell proliferation, colony formation ability, and anchorage-independent growth ability. 26572153_3 taken together, our results showed that foxo1 is a bona fide target of mir-411. in this study, we used lung ac cell lines a549 and calu-3 to investigate the function of mir-411 in cell proliferation and found foxo1 was the target of mir-411. 26858310_1 this indicates that mir-182 directly targets rad51. 20871609_1 fig. 1 the p53 3'-utr contains binding sites for mir-380-5p, a developmentally restricted mirna. 20871609_2 to examine the function of endogenous mir-380-5p, we utilized an lna-modified antisense oligomer to inhibit mir-380-5p . 20871609_4 uv irradiation led to a dose-dependent increase in p53 protein expression that was suppressed by the expression of mir-380-5p . 20871609_5 there was no significant difference in p53 mrna levels following mir-380-5p overexpression , suggesting a predominant role in the regulation of p53 translation rather than mrna stability. 20871609_6 together with our data from es cells , this suggests that mir-380-5p acts to directly regulate p53 translation rather than the stability of the mrna or protein. 20871609_7 thus mir-380-5p can directly attenuate translation via elements found in the p53 3- utr. 20871609_8 importantly, the mature mir-380-5p sequence and mir-380-5p target sequence in the p53 3'-utr are conserved between human and mouse. 25436980_1 tcf7, a wnt signaling-related gene, has been implicated as a critical factor in bone metastasis, and here we show that tcf7 is a direct target of mir-34a. 25436980_2 our data show that the bone metastasis and anti-apoptotic effects found in ras signaling-activated prostate cancer cells require mir-34a deficiency, which in turn aids in cell survival by activating the wnt and anti-apoptotic signaling pathways thereby inducing tcf7 and birc5 expressions. 25436980_3 mir-34a directly binds to the 3'utr of tcf7 and regulates the stability of tcf7 mrna. 25436980_4 these results are consistent with our observation linking mir-34a inactivation to a significantly increased tcf7 expression, required in oncogenic wnt-activated prostate cancer. 26287415_1 moreover, we demonstrated that mir-664 downregulated plp2 expression by directly targeting the plp2 untranslated region. 26287415_2 in the present work, we observed that mir-664 suppressed cmm by directly targeting the 3 ' utr of plp2 rna, which consequently led to inhibition of the pi3k/akt pathway and decreased proliferation. 26287415_3 therefore, our results determine that plp2 is a bona fide target of mir-664. 22735812_1 furthermore, overexpression of mir-146a suppressed tgf--beta-induced hsc proliferation, and increased hsc apoptosis. 22735812_2 bioinformatics analyses predict that smad4 is the potential target of mir-146a. 22735812_3 mir-146a overexpression in tgf--beta1-treated hsc did not decrease target mrna levels, but significantly reduced target protein expression. 22735812_4 these results suggested that mir-146a may function as a novel regulator to modulate hsc activation during tgf--beta1 induction by targeting smad4. 22610915_1 finally, adenomatous polyposis coli , which negatively regulates wnt signaling, was identified as the direct and functional target of mir-155. 22610915_3 these data suggest that mir-155 activates wnt/-beta-catenin signaling by inhibiting apc. 21903578_1 furthermore, gsk-3-beta has a conservative mir-26a seed sequence in its 3'-utr . 21903578_2 however, in both experiments, there was no significant change in gsk-3-beta mrna levels, suggesting that mir-26a predominantly inhibits gsk-3-beta translation. 21903578_3 subsequently, we confirmed the effect of mir-26a on gsk-3-beta translation. 21903578_4 to determine whether mir-26a indeed binds on gsk-3-beta 3'-utr, we transfected asmcsdes-/- with a reporter construct containing the luciferase gene fused to the gsk-3-beta 3'-utr-beta . 21903578_7 overall, our data support a model in which loss of desmin in asmcs up-regulates mir-26a that inhibits gsk-3-beta protein expression, which in turn induces hypertrophy by increasing the expression of smooth muscle-specific markers. 21903578_8 knockdown of desmin in hasmcs also decreased gsk-3-beta protein expression, and transfection of these cells with mir-26a-antagomir increased gsk-3-beta protein expression . 22378788_1 in this study, we showed that both mir-96 and mir-375 act as direct negative regulators on the long 3'-utr pgr isoform. 22378788_2 luciferaseassay, we confirmed that pgr is a primate-specific target of mir-96 and a rhesus monkey-specific target of mir-375, respectively. 22378788_3 we further demonstrated that pgr is a valid target of mir-96 in rhesus monkey and human but not in rodents, whereas the regulation of pgr by mir-375 is rhesus monkey-specific. 20624982_1 the up-regulation of map3k7 and -betatrc by knockdown of mir-10a, predicted by in silico analyses, is consistent with the activation of nf-kappab signal transduction in mir-10a knockdown haec. 20624982_2 consistent with this observation, inhibition of endogenous endothelial mir-10a led to higher regulation of -betatrc than map3k7 at the transcriptional and translational levels . 19808020_1 mir-210 recognizes iscu1/2 as direct target for repression. 19808020_4 nonetheless, through both gain-of-function and loss-of-function assays, these data demonstrate that mir-210 is necessary and sufficient for the down-regulation of iscu1/2 during hypoxia. 19808020_5 taken together with the bioinformatic predictions and the down-regulation of endogenous iscu1/2 by mir-210, these results demonstrate that mir-210 represses gene expression by recognizing the predicted targetsequence in the 3'-utr of iscu1/2. 17264113_1 the porin-regulating srnas, micc and micf, form an extended though imperfect rna duplex with the 5'-utrs of the ompc and ompf mrnas, respectively, whereas mica forms an almost perfect 16 bp duplex encompassing the rbs region of ompa mrna. 25542424_2 as a direct target of microrna-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, psen1 acts as an important executor for the microrna-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on dna damage response pathway. 19177201_1 we demonstrated that agtr1, fgf7, znf537, zic3, and ikbke are true mir-155 target genes in hl. after cotransfection with anti-mir-155 oligonucleotides, significantly increased relative luciferase expression levels were obtained for agtr1, znf537 , fgf7 , zic3, maf, and ikbke, implying that these genes are true mir-155 target . 22016468_2 mir-622 functions as a tumor suppressor by targeting k-ras. 22016468_3 however, the mir-622 mimic did not affect the k-ras mrna expression levels, suggesting that mir-622 regulates k-ras mrna translation without affecting accumulation levels . 22016468_4 these results demonstrated that k-ras is a potential target of mir-622; we verified this with the luciferase reporter assay. 22016468_5 in contrast, the luciferase activity was not affected by mutant type mt-k-ras plasmid cotransfection with mir-622 mimic and mir-622 inhibitor, potentially because mir-622 was unable to recognize the complete mutant binding sites of k-ras mrna, thereby disrupting the interaction between mir-622 and k-ras . 22016468_6 these data indicate that k-ras is targeted directly by mir-622. 22016468_7 taken together, these results indicated that k-ras is a functional targetin the growth retardation induced by mir-622. 20421599_1 using this assay, we found that the 3- utr of cdh-3 can confer a significant mir-52-dependent inhibition of translation . 20421599_2 we then tested whether the mir-51 family can regulate the cdh-3 3- utr in the hypodermis, in which the mir-51 family is expressed and gfp expression can be assayed easily . 20421599_3 taken together, these data show that mir-52 directly regulates the cdh-3 3- utr in vivo. 20421599_4 we also tested if the cdh-3 3- utr is regulated by the mir-51 family in the arcade cells, where regulation of cdh-3 by mir-51 family mirnas may be required for pharyngeal attachment. 20421599_5 these data suggest that the mir-51 family directly regulates cdh-3 expression in the arcade cells. 20421599_6 these data suggest that at least one function of the mir-51 family during pharyngeal morphogenesis is to downregulate cdh-3. 23977013_1 the mir-200 family members target both zeb1 and zeb2. 23977013_2 the mir-200 family is divided into two groups according to their sequence seed: group 1 and group 2 . in isolated glomeruli, of 16-wk-old lp animals, mir-141, mir-200a, mir-200b and mir-429 were significantly down-regulated compared to np offspring . 23977013_3 the mir-200 family members target both zeb1 and zeb2 . in lp offspring, the gene expression for collagen 1alpha1, collagen 1alpha2 and zeb2 gene expression were significantly increased in isolated glomeruli . 23977013_4 surprisingly, unchanged findings for mrna expression for desmin, e-cadherin, fibronectin, tgf--beta1, zeb1 and zo-1 were found for both groups . 22009755_2 luciferase reporter assay and expression analysis showed that timp3, a tissue metalloproteinase inhibitor, is a common target of mir-221/222 and -181b. 22009755_3 these data suggest a cumulative inhibitory effect of mir-221/222 and -181 on timp3 expression in the ohtr cells. in summary, growth factor signaling is facilitated in ohtr cells due to reduced timp3 level that, in turn, is regulated by mir-221/222 and -181b in these cells. 22009755_4 these data suggest the role of mir-221/222/181b and timp3 in facilitating akt-mediated proliferation of tamoxifen-resistant cells. 21051663_2 western blot analysis showed that transfection of mir-1 significantly decreased the expression level of endogenous pim-1 protein . in addition, there was no significant decrease in the mrna level of pim-1 on mir-1 transfection, although a tendency for the decreased expression of pim-1 was observed in spindle-shaped smcs . 21051663_3 together, our results demonstrated that pim-1 is a direct regulatory target of mir-1 in smcs. 21051663_4 given that pim-1 is known to stimulate the proliferation of smcs, our results provided an explanation for mir-1-mediated smc proliferation repression. 21853268_1 microrna-132 target hb-egf in mast cells. 21853268_2 first, we checked the functionality of mir-132 binding sites in the 3' -utr of human hbegf. 21853268_3 for this experiment the luciferase reporter gene was fused with the 3' utr sequences of human hbegf, and this vector was co-transfected with pre-mir-132 or negative control oligos into cho cells. 21853268_5 next, we examined whether hbegf is regulated by mir-132 at the protein level in mouse mast cells. 21853268_6 thus, the exogenous delivery and knockdown of mir-132 clearly prove that mir-132 controls hbegf protein levels in activated mast cells. 19073608_3 bioinformatic predictions suggest that the human egfr mrna 3'-untranslated region contains three microrna-7 target sites, which are not conserved across mammals. 19073608_4 we found that mir-7 down-regulates egfr mrna and protein expression in cancer cell lines via two of the three sites, inducing cell cycle arrest and cell death. 19073608_5 because mir-7 was shown to decrease egfr mrna expression, we used microarray analysis to identify additional mrna targets of mir-7. 19073608_7 furthermore, mir-7 attenuated activation of protein kinase b and extracellular signal-regulated kinase 1/2, two critical effectors of egfr signaling, in different cancer cell lines. 19073608_8 these data establish an important role for mir-7 in controlling mrna expression and indicate that mir-7 has the ability to coordinately regulate egfr signaling in multiple human cancer cell types. 26095125_1 as expected, we observed a significantly lower expression of direct mir-29 ecm protein targets in pscs transfected with mir-29 mimics compared to cells transfected with control mimic. 25897249_1 mir-27a directly targets various regions of the 3'-utr to repress the endogenous expression of foxo1 in breast cancer. 26840300_1 taken together, these data indicated that mir-30a-5p, mir-30b-5p and mir-30e-5p directly target the 3- utr of mbnl2, whereas mbnl3 is a direct target gene of mir-30a-5p and mir-30e-5p only. 24480980_2 these findings indicated that crk was a direct target of mir-126 and negatively regulated by mir-126 in hscs. 24480980_3 overexpression of mir-126 inhibited hscs activation and migration maybe through directly inhibiting crk expression and indirectly disturbing f-actin. 21481725_1 we identified the pten gene as a target of mirna-221/-222. 21481725_2 meanwhile, overexpression of mir-221/-222 in hek293 cells led to down-regulation of pten expression . 21481725_3 together, these data demonstrate that the pten gene is a target of mir-221/-222. 21481725_4 it is noted that during the preparation of the manuscript, a report was published that showed the pten gene is a target of mir-221/222, supporting our observations . . 21481725_5 together these observations demonstrate that regulation of pten expression by mir-221/-222 leads to radioresistance. in summary, we demonstrate that mir-221 and mir-222 are involved in the regulation of radiosensitivity by targeting the pten/akt pathway. 26545810_1 calml5 mrna was up-regulated by the znf750 transcription factor and then stabilized by the long noncoding rna tincr. 26545810_2 taken together, these findings suggested a model in which p63-activated znf750 induces calml5 expression, with calml5 mrna then post-transcriptionally stabilized by tincr. 26545810_3 tincr rna interactome analysis sequencing identified apeak in the calml5 3'-untranslated region , indicating that calml5 mrna could be a tincr stabilization target . 26545810_4 calml5 mrna, but not the hbp1 control differentiation gene, was significantly less stable with tincr depletion , confirming that tincr promotes calml5 mrna levels through stabilization. 23405269_1 microrna-122 dependent binding of ago2 protein to hepatitis c virus rna is associated with enhanced rna stability and translation stimulation. 23405269_2 here,we show that argonaute 2 protein binds to the hcv 5'-utr in a mir-122-dependent manner, whereas the hcv 3'-utr does not bind ago2. 25662849_1 quantitative reverse transcription pcr and western blotting analysis revealed that the expression of pten was increased after downexpression of mir-494-3p in glioma cells . 25662849_2 mir-494-3p can target the pten mrna. 25662849_3 both in the glioma cell lines u251 and u87, mir-494-3p inhibitor can enhance the expression of pten to further suppress activated-akt signaling and reduce the ability of invasion and proliferation in glioma cell lines. 26452129_1 the overexpression of mir-506 resulted in a significant decrease in the luciferase activity of the construct containing the wild-type 3'-utr of ezh2. 26452129_2 this regulation was abolished when the nucleotides in the putative binding site were mutated , indicating that the mir-506-mediated regulation of ezh2 expression depended on its binding to a specific seed region in the ezh2 3'-utr. 26452129_3 therefore, ezh2 plays an important role in the proliferation and metastasis of colon cancer cells, potentially by acting as a mediator of mir-506 function. 22773832_1 the luciferase reporter assay verified lepr as a direct target for mir-21 and mir-130a. 22773832_2 together, these results confirmed that mir-21 and mir-130a have a direct effect on lepr, mediated through 3'-utr target sites. 22773832_3 our data identified lepr as a novel target for mir-21 and mir-130a, implicating their role in the inhibition of wound healing and pathology of vus. 22773832_4 our study identified and confirmed lepr as a novel target for the most induced mir-21 and mir-130a in epidermis, suggesting that exogenous leptin would not improve healing of chronic vus. 21730150_1 in pancreatic -beta cells, c-rel and p65 of the nf-κb family activated the mir21 gene promoter and increased mir-21 rna levels; mir-21 in turn decreased the level of pdcd4, which is able to induce cell death through the bax family of apoptotic proteins. 20795863_1 we show that mir-184 binds bin3 3' utr and while bin3 mrna expression was equal in both cell lines, the protein expression was inversely correlated with mir-184 expression. 20795863_2 these results indicate that mir-184 can bindto the predicted binding site in bin3 3'-utr, and influence post-transcriptional regulation of bin3 expression. 20795863_4 western blotting of bin3 protein in both cell lines demonstrated a higher level in sra01/04 cells compared to hle-b3 , in agreement with the much lower expression of mir-184 in sra01/04 compared to hle-b3 cells. 26741509_1 we found that mir-454 targeted the 3'-utr of cxcl12 mrna to inhibit its protein translation in human lung epithelial cells. 26741509_3 the luciferase activities in these cells showed that mir-454 targeted 3'utr of cxcl12 mrna to inhibit its translation . 22252650_1 in addition, we demonstrated that cpt induced apoptosis in cancer cells by mir-125b-mediated mitochondrial pathways via targeting to the 3'-untranslated regions of bak1, mcl1, and p53. 20874002_2 these data indicate egfr mrna is a functional downstream targetfor mir-146b-5p. 20874002_3 these results suggest that mir-146b-5p regulation of egfr protein expression is due to inhibition of translation via direct binding to egfr mrna. 20979124_2 furthermore, we transfected mir-194 inhibitors with luciferase reporter constructs to hepg2 cells, in which mir-194 was highly expressed, to study the knockdown effects of mir-194 in epithelial cells . 20979124_3 the inhibitors significantly released the repression by mir-194 on the luciferase genes with the 3'-utrs of n-cadherin, hbegf, rac1, ptpn12, itga9, socs2, and dnmt3a. 20979124_4 we also found that mir-194 inhibitors caused a significant increase of endogenous n-cadherin, hbegf, and igf1r mrna levels in hepg2 cells . in contrast, the inhibitors did not affect the expression of dnmt3b, which does not have a predictable mir-194 binding site in its 3'-utr in conclusion, mir-194 may suppress metastasis of liver cancer cells by targeting several genes that function at the different stages of hcc progression and metastasis. 22344686_1 mir-21 is located in the 3- utr of tmem49 gene. 25749519_1 the increased expression of myo10 was also observed in nsclc, particularly in lymph node-positive ones ,4b, and was negatively correlated with mir-124 level in nsclc tissue biopsies .4c. this prompted us to study the expression of myo10 in ectopic mir-124 expressed cells revealing a significant down-regulation .4d. ectopic mir-124 repressed the activity of myo10 wild-type 3'-utr reporter constructs in dual luciferase reporter assays ,4f, while mutation in mir-124-binding site completely abrogated this repression. 25749519_2 therefore, it was demonstrated that the myo10 expression could be directly regulated by mir-124 via conserved seed-matching sequences and correlates with the node metastasis of nsclc disease. 19584269_1 endogenous mir-661 expression was positively regulated by the c/ebpalpha transcription factor, which is down-regulated during cancer progression. 19584269_2 c/ebpalpha directly interacted with the mir-661 chromatin and bound to mir-661 putative promoter that contains a c/ebpalpha-consensus motif. in addition, we found that the level of mta1 protein was progressively up-regulated, whereas that of mir-661 and its activator, c/ebpalpha, were down-regulated in a breast cancer progression model consisting of mcf-10a cell lines whose phenotypes ranged from noninvasive to highly invasive. 19584269_3 c/ebpalpha expression in breast cancer cells resulted in increased mir-661 expression and reduced mta1 3'utr-luciferase activity and mta1 protein level. 19584269_5 we believe our findings show for the first time that c/ebpalpha regulates the level of mir-661 and in turn modifies the functions of the mir661-mta1 pathway in human cancer cells. 19584269_6 based on these findings, we suggest that mir-661 be further investigated for therapeutic use in down-regulating the expression of mta1 in cancer cells. 26609479_1 we identified rab11a as a direct target of mir-320a and showed that its expression was upregulated in tumor samples and inversely correlated with the expression of mir-320a. 26609479_2 rab11a was identified as a target gene of mir-320a and shown to mediate its tumor suppressor effect via the modulation of associated proliferative signaling pathways. 26609479_3 collectively, these results suggest that rab11a is a target of mir-320a. 26609479_4 we identified rab11a as a direct target of mir-320a in bc cells, and showed that the tumor suppressor activity of mir-320a is mediated by the modulation of rab11a expression. 26909612_1 both in vitro and in vivo experiments showed that ectopic stable expression mir-194 suppressed proliferation, migration, invasion and metastasis and induced apoptosis in nsclc cells and that this suppression could be reversed by reintroducing forkhead box a1 , a functional target of mir-194. 26909612_2 we also provide experimental evidence that mir-194 regulated cellular function via directly interacting with the foxa1 mrna at the 3'-utr. 26909612_3 in this study, we have demonstrated a mechanism that mir-194 was decreased in clinical nsclc tissues compared to adjacent normal lung tissues and that mir-194 played a critical role in nsclc progression by regulating cell proliferation and invasion via negatively regulate foxa1. 25486484_2 2c, downregulation of mir-155 results in restoration of stat4 expression in myla ctcl malignant cells. 25486484_3 this suggests that the observed disease-associated upregulation of mir-155 may be responsible for downregulation of stat4 and subsequent loss of th1 phenotype in malignant t cells. 20451302_1 we tested whether mir-144 also regulates endogenous atxn1 levels within cells at the posttranscriptional level. 20451302_2 atxn1 3=utr contains 3 conserved and 2 nonconserved binding elements for mir-144 . 20451302_3 first, overexpression of either mir-144 or -101 duplex rna and atxn1 sirna in 293t cells resulted in a significant decrease in endogenous atxn1 protein levels as assessed by western blotting . 20451302_4 the results indicated that mir-144 and -101 reduced considerably atxn1 protein expression suggesting that both mirnas act as translational repressors. 20451302_5 we also noticed that mir-101 and -144 consensus elements are evolutionary conserved and partially overlap within atxn1 3' utr, suggesting that the mechanism of atxn1 regulation by mir-144 and -101 is conserved in primates. 20451302_6 taken together, our results suggest that mirnas, and mir-144 in particular, are an important component of atxn1 regulatory pathway. 20451302_7 fig. 4. regulation of ataxin 1 expression by mir-144 and mir-101. in conclusion, these data indicate that mir-144 has the ability to bind directly to the atxn1 3' utr and suppress the translation of atxn1. 25483699_2 pylori-induced gastric inflammatory reaction via up-regulating microrna-155 to inhibit th17 responses, implying that the microrna-155/il-17 pathway was involved. 25483699_3 further study is required to elucidate the relationship between mirna-155 and il-17. 25483699_4 we found that the production of il-17 was significantly increased after the expression of mirna-155 being down-regulated; however, the production of il-17 was significantly decreased after the expression of mirna-155 being upregulated. 19524507_6 indeed, rhoa re-expression partially reverses mir-31-imposed metastasis suppression. 26191190_1 in vitro reporter assay suggested ezh2 is a direct target gene of mir-1297. 26191190_2 furthermore, knockdown of ezh2 have the same effect with mir-1297 overeexpression in hepatocellular carcinoma cells. 26191190_3 these findings provide evidence that mir-1297 plays a key role in inhibition of the hepatocellular carcinoma cells proliferation, and enhancing cell apoptosis through targeting ezh2, and strongly suggest that exogenous mir-1297 may have therapeutic value in treating hepatocellular carcinoma. 25936394_2 gk5 downregulation is associated with mir-135b expression in glioblastoma. 25936394_3 gk5 is a target of mir- 135b in u87mg glioblastoma cells. 25175984_1 in addition, we demonstrated that decreased expression of ship1 in the aml cell lines was a consequence of increased levels of mir-155 and can therefore be reversed in vitro through inhibition of mir-155, with subsequent inhibition of cell proliferation and promotion of cell apoptosis. 25175984_2 in conclusion, expression of the ship1 protein is targeted by mir-155 in aml. 25175984_3 mir-155 acts as an onco-mir, and the mir-155/ship1/pi3k/akt signaling pathway could play an important role in the pathogenesis of aml. 26201895_2 the results demonstrated that ccnd3 was significantly downregulated while mir-138 was upregulated in h460 and spc-a1 cells. 26201895_3 since we showed that ccnd3 was directly targeted by mir-138 and mediated by mir-138 in nsclc, we speculated that ccnd3 could have functional mechanisms in regulating nsclc. 26201895_4 overall, our serial two-step transfection experiments all demonstrated that the anti-cancer effects of mir-138 upregulation were all reversed by ccnd3 overexpression, thus suggesting that ccnd3 was actively involved in mir-138 regulation in nsclc. 25384965_3 induction of mir-193b in ssc fibroblasts suppressed, and accordingly, knockdown of mir-193b increased the levels of messenger rna and protein for upa. 26609496_1 since mir-182 and mir-96 target reck, we examined the effect of knocking down their expression, as well as that of mir-183 from the same cluster, on the level of reck mrna expression by transfecting their anti-mirs in ht-1080 and bph-1 cells. 26609496_2 we examined the ability of mir-182 , which can target reck, to control cell surface mt1-mmp activity. 19287972_2 these results indicated that bokas is a negative regulator of apoptosis induced by bok. 26885452_2 collectively, our findings indicate that mir-610 exerts its function by directly targeting hdgf. 26885452_3 furthermore, hdgf is revealed to be a direct and functional target of mir-610, which is negatively correlated with mir-610 expression in crc tissues. 26885452_4 taken together, our data showed that mir-610 negatively modulated hdgf expression by directly binding to its 3'-utr. 26885452_5 further study showed that hdgf is a direct target gene of mir-610, and its expression inversely correlated with mir-610 expression in crc clinical specimens. 22028478_1 two mir-130a binding sites were identified in the 3'-untranslated region of the smad4 mrna. 22028478_2 these data support the idea that mir-130a is involved in translational repression of smad4 mrna. 22028478_3 this shows that overexpression of mir-130a can decrease the smad4 level sufficiently to reduce expression from a smad4-dependent luciferase reporter plasmid. 22028478_4 together, these results show that the reduced smad4 level in cells with high mir-130a expression lowers the sensitivity to tgf--beta1 stimulation and allows the cells to continue their proliferation at a higher rate without inducing apoptosis or granulocytic maturation. 22028478_5 together, these results show that mir-130a appears to regulate smad4 expression by binding to the 2 predicted targetsites in smad4 3'-utr. 22028478_6 this shows that mir-130a does take part in regulating smad4 in this aml-derived cell line. 17540599_1 one important role of mir-34a is the modulation and fine-tuning of the gene expression program initiated by p53 for mir-34a-responsive genes are highly enriched for those that regulate cell-cycle progression, apoptosis, dna repair, and angiogenesis. 23516376_1 from the eight genes that were tested, including sox11, six were down-regulated in response to hsa-mir-204 mimic; the five reduced in h36ce cells were also significantly elevated following transfection with hsa-mir-204 inhibitor . 23204229_1 mir-204 target and suppresses sox4 and ephb2 expression. 23204229_2 as shown in fig.5c, ectopic expression of mir-204 markedly decreased, while inhibition of mir-204 significantly elevated, the reporter luciferase activities , suggesting that mir-204 post-transcriptionally inhibited sox4 and ephb2 expression. 23204229_3 this observation indicates mir-204 may act as regulator for sox4 and ephb2 expression in clinical glioma specimens. 20655737_1 mir-193b directly represses the expressions of ccnd1 and ets1 through their 3'-utrs. 20655737_2 these data suggest that mir-193b may repress the mrna expressions of ets1 and ccnd1 at posttranscriptional level by directly targeting their 3'-utrs. 20655737_3 all these results reveal that ets1 and ccnd1 are the genuine target of mir-193b. 25783790_1 these data confirmed that mir-34a regulated notch1 by directly interacting with the 3'-utr of the gene in mcf-7 cells. 19486339_2 at least 50% of the tumor samples showed a greater than two-fold increase in the expression for mir-18 and for the mir-106b-25 cluster when compared with the corresponding paired non-tumor samples. 19486339_3 knock-down studies for the mir-106b-25 cluster, which includes mir-106b, mir-93 and mir-25, showed that the expression of the cluster is necessary for cell proliferation and for anchorage-independent growth. 19486339_5 we further identified the transcription factor e2f1 as a target gene for mir-106b and mir-93 and it is likely that one of the roles of the mir-106b-25 cluster is to prevent excessively high e2f1 expression, which may then cause apoptosis. 19486339_6 we conclude that there is aberrant expression of micrornas encoded by the oncogenic mir-17-92 cluster and the mir-106b-25 cluster in hepatocellular carcinoma. 20226166_1 we performed a qpcr analysis of mir-375, yap isoform 1 , and yap isoform 2 in 48 pairs of hcc tumor and matched adjacent non-tumor tissues. 20226166_2 it is noteworthy that both isoforms of yap contain the same 3'-utr regions, and the results showed that mir-375 was significantly down-regulated in hcc tumor tissues, while both isoforms of yap were up-regulated in hcc tumor tissues, suggesting yap is a target of mir-375 . 20226166_3 yap is a direct target of mir-375. in contrast, the luciferase activity of the mutant reporter was unaffected by cotransfection of mir-375 , indicating mir-375 suppressed gene expression through mir-375-binding sequence at the 3'utr of yap. 26331031_1 more specifically, that study showed that mir-19a, mir-101, and mir-130a co-regulate the 3'-utr of atxn1 through the inhibition of atxn1 translation. 26331031_2 in a reporter assay, which is the simplest and most straightforward method of validation of mirna-mrna interactions, mirs 19a, 101, and 130a were shown to downregulate the expression of atxn1. 26331031_3 taken together, these findings show that mirna-mediated posttranscriptional regulation of the atxn1 gene may modulate sca1-related neuropathology by affecting protein levels. 26456956_1 furthermore, mir-329 significantly regulated cell invasion by targeting brd4 but had noeffecton cell proliferation and apoptosis. 26456956_2 furthermore, we identified that mir-329 could regulate hcc cell invasion via targeting brd4. in sum, these results implied that mir-329 could regulate brd4 expression by binding its 3'-utr. 26456956_3 to better understand the mechanisms of mir-329 in hcc cell invasion, we identified mir-329 regulating brd4 in hcc using luciferase reporter and western blot assays. 25682742_1 in this study, we not only showed that anubl1 as an oncogene was upregulated and could promote proliferation of sgc-7901 cells, but also demonstrated that its over expression led to a strong decrease of mir-182 expression and expression of anubl1 was in turn directly downregulated by mir-182, thereby establishing a negative feedback loop between mir-182 and anubl1. 25682742_2 the result showed that mir-182 indeed downregulated anubl1 mrna expression in sgc-7901 cells . 25682742_3 all the results confirmed that mir-182 negatively regulates protein-coding gene anubl1 expression by targeting its 3'utr. 19223090_1 in the present study, we found that a microrna mir-126 has a binding site in 3'-untranslated region of the vegf-a mrna. 19223090_2 mir-126 interacts with vegf-a 3'utr. in order to test whether mir-126 is indeed capable of regulating vegf-a protein expression via the binding site in vegf-a 3'utr, we cloned the predicted mir-126 binding site from cdna library downstream the firefly luciferase coding region in pmir-reporttm luciferase vector . 19223090_3 these results suggested that mir-126 could inhibit vegf-a expression. 18794849_2 in addition, to validate whether reck is a direct target of mir-21, we mutated the mir-21 binding site in the 3'utr of reck and observed loss of repression . 18794849_3 these results all indicate reck is a direct target of mir-21. 26302774_1 these data strongly suggest that mir-376b may target nfkbiz and stat3 in hepatocytes, and the downregulation of mir-376b in the regenerating liver tissue may lead to the increased expression of nfkbiz and stat3. 26080838_1 the result indicated that the fragment at the 3'-utrs of the rps6kb1 mrna was the complementary site for the mir-195 seed region, suggesting that rps6kb1 was the direct target of mir-195. 26080838_2 overall, mir-195 negatively regulated rps6kb1 expression in vitro and in vivo. 25216407_1 the expression level of mir-185, indicated by real-time pcr, was significantly reduced , while that of hif-2alpha was increased in the sw620 colon cancer cells. 25216407_2 to monitor the effect of mir-185 overexpression on hif-2alpha expression in target cells expressing low levels of mir-185, the mir-185 mimic and scrambled control were delivered into sw620 cells. 22167021_4 to test whether igf1 and il1rap are direct targets of mir-29 regulation, we cloned the 3- utrs of each gene into a reporter plasmid and performed dual luciferase assays in nih3t3 cells, while over-expressing mir-29a . 22167021_5 when mir-29a was overexpressed, the reporters containing the igf1 and il1rap 3- utrs were significantly down-regulated relative to the empty reporter . 19487295_1 we focused on mir-129 that exerted significant growth inhibition and induced cell death upon transfection with a mir-129 precursor in bladder carcinoma cell lines t24 and sw780 cells. 19487295_4 using luciferase assays, we documented a direct link between mir-129 and the two putative targets galnt1 and sox4. 23492773_1 mir-128 inhibition of sirt1 led to an increase in acetylated p53 and its transcriptional targets. 26229046_1 these results suggest that the 3'-utr of human cyp3a4 represses the activity in association with the regulation of mir-27a. 26229046_2 hsa-mir-27a level in human livers was significantly in spearman rank correlated with cyp3a4 mrna level and protein level as well as showed significant linear regression with cyp3a4 mrna level and protein level . 24821285_1 microrna-200c downregulates xiap expression to suppress proliferation and promote apoptosis of triple-negative breast cancer cells. 18802929_3 more interestingly, hsa-mir-34b was found to be down-regulated only in bl cases that were negative for myc translocation, suggesting that this event might be responsible for c-myc deregulation in such cases. 18802929_4 this hypothesis was further confirmed by our in vitro experiments, which demonstrated that increasing doses of synthetic hsa-mir-34b were able to modulate c-myc expression. 18802929_5 these results indicate for the first time that hsa-mir-34b may influence c-myc expression in burkitt lymphoma as the more common aberrant control exercised by the immunoglobulin enhancer locus. 26549025_1 mechanistically, bc032469 could directly bind to mir-1207-5p and effectively functioned as a sponge for mir-1207-5p to modulate the derepression of htert. 26549025_2 thus, bc032469 may function as a cerna to impair mir-1207-5p-dependent htert downregulation, suggesting that it may be clinically valuable as a poor prognostic biomarker of gastric cancer. 26549025_3 our previous study has demonstrated that mir-1207-5p and mir-1266 could inhibit htert expression at the post-transcriptional level by directly binding to the 3'-utr of the htert mrna. 26549025_6 we hypothesized that lncrna bc032469 might have the same interaction with mir-1207-5p and mir-1266 to regulate expression of htert. 26719072_2 the result showed that mir-203 downregulated sik1 expression by targeting its 3'utr in pancreatic cancer and that sik1 was downregulated in pancreatic cancer cells, due to the overexpression of mir-203. 26719072_3 the results showed that sik1 protein was significantly downregulated in the cells transfected with pre-mir-203. 23601686_1 to more directly test if socs-1 was regulated by mir-155, we measured socs-1 mrna in wild type andmir155-/- cd8+ t cells as well as in cells overexpressing mir-155 or scrambled control mir. 23601686_2 we found that the amounts of socs-1 transcripts were inversely related to the cellular content of mir-155, with the highest concentration of socs-1 in mir155-/- cells and the lowest in mir-155 transduced cells . 23601686_3 these results were further confirmed at the protein level, indicating that mir-155 is a critical regulator of socs-1 translation in cd8+ t cells . 23601686_4 together, these results demonstrate that socs-1 is negatively regulating the effector cd8+ t cell response to virus and cancer and highlight the importance of socs-1 downregulation by mir-155 for efficient cd8+ t cell responses. 26095359_1 of note, glua1 mrna expression was unaffected by mir-137, suggesting that the changes in glua1 protein levels by mir-137 is regulated at the level of translation rather than transcription . 26095359_2 we observed a significant increase in surface glua1 expression at synapses of sponge-mir-137-expressing hippocampal neurons, whereas sglua1 levels were reduced during mir-137 overexpression , supporting the notion that ampar subtype glua1 is directly targeted by mir-137. 22544395_1 these results demonstrate that, as predicted, mir-10a can directly target sequences in the 3'utr of bcl-6 and ncor2. 20505319_1 figure 2. posttranscriptional repression of met expression by mir-133b. 20505319_2 these data suggest that the 3'-utr of met was a functional target site for mir-133b in these cultured cancer cell. 22773185_1 taken together, we conclude that mir-9 targets socs5 in endothelial cells and activates the jak-怱tat signalling pathway. 26693054_2 as shown in figure 2b, the expression level of pxn mrna in all the cell lines was negatively associated with mir-212 expression. 26693054_4 the results make it evident that mir-212 effects pxn expression by directly binding to the 3'-utr region of pxn. 26693054_5 transfection of mir-212 results in a marked reduction of pxn mrna levels in both cell lines compared with that of the nc cells. 22963810_1 a luciferase reporter assay showed that mir-1 regulation was established by pairing to a complementary binding site within the et-1 3'utr. 22963810_5 here, et-1 levels were significantly induced after mir-1 silencing, suggesting that 2-om blocks mir-1-induced et-1 repression, providing further confirmation that mir-1 target et-1. 22963810_6 taken together, our data demonstrated that mir-1 could bindwith the targetsite in et-1's 3'-utr to inhibit et-1 expression. 26282675_1 therefore, we selected hbp1 as a potential target of mir-21. 26282675_2 taken together, hepatic expression of mir-21 was increased in dietary obese mice and livers of human patients with nafld/nash, and hbp1, as a potential target of mir-21, showed reduced expression in livers of obese mice and human patients with nafld . 26282675_3 our findings suggested that the crosstalk between mir-21 and hbp1 might play an important role in hepatic lipid accumulation. 20668041_4 our data suggest that overexpressed mir-128a, mir-516a-3p, and mir-155 target wee1 which was down-regulated in hormonally silent and gh±p pituitary adenomas. 26872375_1 we also identified dna methyltransferase enzyme dnmt1 as a target of mir-148a-3p. 26872375_2 we also determined that dna methyltransferase enzyme dnmt1 as an inhibitory target of mir-148a-3p. 26872375_3 taken together, these results indicated that dnmt1 was a target gene of mir-148- 3p. 21940949_1 in srf-depleted smcs, a mir-21 inhibitor increased 3-utr luciferase activity but failed to alter activity of the mir-21 mirna response element mutated pten 3'-utr . 21940949_2 consistent with these findings, mir-21 levels were elevated in srf-depleted smc clones and pools compared with their respective controls. 26580398_2 these experiments demonstrated that mir-181a targets etv6/runx1, and they suggested that the fusion gene and mir181a1 can regulate each other. 26580398_3 this induction partially altered the lymphocytic differentiation as shown by the cd10 hyperexpression decrease in cells from two of three etv6/runx1-positive samples , suggesting that the level of mir-181a expression is important for the perturbation of the lymphocytic differentiation program in etv6/runx1 all. 26280272_1 rno-mir-133b-5p might inhibit hsp70 expression by directly targeting the hsp70 3'-utr. 26280272_3 the binding free energy of rno-mir-133b-5p and hsp70 was -27.9 kcal/mol . 26280272_4 these results showed that rno-mir-133b-5p, when combined with the hsp70 3'-utr, inhibited the expression of hsp70 in a dose-dependent manner. 19118351_2 and sstt mrnas, both shown by lacz translational fusions to be negatively regulated by gcvb in e. coli 10-fold. 22659882_1 in the inflammatory network, il-6 and socs-1, regulated by mirnas let-7 and mir-155, respectively,appeared as central nodes. 22659882_2 let-7a also target il-6 ; thus decrease of let-7a could contribute to the increase of il-6 observed in vili. 26393682_1 let-7 is known to be a negative regulator of the ras oncogene. 26393682_2 our results support the hypothesis that let-7 is a tumor suppressor that negatively regulates ras, also in es, and that hif-1alpha may contribute to the aggressive metastatic behavior of es. 26119756_1 the presence of mir-302 target sites within the 3' utrs of baf170 and baf53a suggested direct regulation by mir-302. 26119756_2 these data demonstrate that mir-302a can repress baf53a and baf170 expression. 20150764_1 the antitumor activity of ad-mir122 was probably due to the induction of apoptosis and/or cell cycle arrest in cancer cells through inhibiting bcl-w and/or ccng1 expression. 21518477_1 the results showed that compared with the normal people, the expression of mir-143 in al patients was significantly decreased , which significantly increased after complete remission; besides, the expression of mir-143 was negatively correlated with the expression of dnmt3a mrna, a known targetgene of mir-143. 21362569_1 the 3'-utr of blimp1 mrna is predicted by targetscan to contain a single mir-125b binding site that is well-conserved from amphibian to mammals. to test the hypothesis that blimp1 mrna may be a direct target of mir-125b in skin, we constructed a luciferase reporter for wt blimp1 3'-utr, as well as a control reporter in which the mir-125b binding site of the blimp1 3'-utr was mutated . 21362569_3 elevated mir-125b resulted in strong repression of the wt blimp1 3'-utr reporter but not a mutant blimp1 3'-utr reporter lacking the mir-125b binding site . 21362569_4 furthermore, when mir-125b was repressed by transfecting anti-sense lna probes against mir-125b into cultured mk, wt blimp1 3'-utr reporter activity was significantly upregulated in contrast to the control reporter . 21362569_5 taken together, these data indicate that blimp1 mrna is a direct and functionally relevant target of mir-125b in skin keratinocytes. 20951849_1 human bdnf mrna and bdnfos lncrna form in-vivo rna篓crna duplexes in brain, suggesting the possibility of post-transcriptional cis-regulation, by bdnfos, of bdnf. 18460397_1 differential expression of pten-targeting mir-19a and mir-21 modulates the pten protein levels and the cs phenotype, irrespective of the patient-mutation status, and support their roles/r/nas genetic modifiers in cs. 21730286_1 such an inhibitory function of mir-146a on gliomas is largely through downregulation of notch1, which plays a key role in neural stem cell maintenance and is a direct target of mir-146a. 21730286_2 western blot analysis further showed that ectopic mir-146a in malignant astrocytes induced a dramatic reduction of notch1 protein, especially the processed intracellular nicd, which is the most predominant form in these glia cells . 21730286_3 the inhibitory role of mir-146a on notch1 is mainly through posttranscriptional control since it does not change the mrna level of notch1 . 22747855_1 indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in igf1r mrna and protein, and a luciferase reporter assay indicated that the 3'utr of igf1r is a target of both mir-376a and mir-376c. 22747855_2 establishment of igf1r as a target of mir-376a/c. 22747855_3 with a control luciferase vector, respectively, indicating that the stable expression of both mirnas leads to further significant down-regulation on the 3'utr of igf1r , thus establishing igf1r as a target of both mir-376a and mir-376c. 22510476_1 mir-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor a. microrna mir-126 has a binding site in 3 -untranslated region of the vegf-a mrna. 22510476_2 mir-126 was naturally complementary to the vegf and the interaction can inhibit the overexpression of vegf in tumor cells. 22510476_3 mir-126 could efficiently down-regulate vegfa expression through the interaction with the vegfa 3'-untranslated region. 22510476_4 however, no decrease was observed in a549 cells transfected with a mutant vegf 3'-utr , suggesting that vegfa is a direct targetgene of mir-126. 26339338_1 together these data support the notion that bcl-2 is a direct target of mir-497. 26339338_2 mir-497 negatively regulates bcl-2 protein expression at the posttranscriptional level 23733368_3 we also identify hur as a novel target of mir-146 and find that hur acts to promote endothelial activation and leukocyte recruitment in response to il-1b. 23899543_1 mir-106a and mir-106b overexpression inhibited the expression of several other autophagy genes, including atg12. 20885358_1 some preliminary studies have shown that abcg2 is the targetgene for mirna-328. 23154414_1 moreover, such a persistent expression of bam in spermatocytes was recapitulated by specifically mutating the putative mir-275/mir-306 recognition site at the bam 3'utr. in summary, these results demonstrate that overexpression of mir-275 or mir-306, but not mir-7 or mir-317, is sufficient to repress bam protein accumulation. 23154414_2 these data suggest that both mir-275 and mir-306 could cooperate in downregulating bam protein in spermatocytes. 22714950_1 reporter genes with putative mir-181a binding sites from the tgfbr1 and tgfbrap1 3'-untranslated regions were downregulated in the presenceof mir-181a, suggesting that mir-181a binds tgfbr1 and tgfbrap1 3'-utrs. 22714950_2 we used quantitative reverse transcription pcr to determine expression level of potential mir-181a targetgenes in the transfected mscs. 22714950_3 mir-181a expression caused significant downregulation of tgfbr1 and tgfbrap1 mrna levels . 22714950_4 western blot analysis showed that the protein levels of tgfbr1 and tgfbrap1 were also downregulated . 22714950_5 expression of tgfbr1 and tgfbrap1 mrna and protein was also analyzed in mscs transfected with anti-mir-181a. 18645025_1 therefore, we determined the role of mir-451 in the regulation of mdr1 expression. 18645025_3 to examine whether mdr1 is indeed functionally targeted by mir-451, the segment of mdr1-3'-utr containing the mir-451 complementary site was cloned into the 3'-utr of a luciferase reporter system. 18645025_4 the finding that the mir-451 target mdr1 suggested that down-regulation of expression of this mirna contributes to the cancer drug resistance; therefore, the restoration of a mir-451 level in the resistant mcf-7/dox cells may increase their sensitivity to dox. 21790228_1 in order to further proved its reliability, mutants of cox-2 3'-utr was constructed by deleting the mir-143 target site and cotransfected into t24 cells together with mir-143. 21790228_2 the luciferase expression of mutant 3'-utr of cox-2 was no longer subject to be regulated by mir-143. 21790228_3 this results further confirmed that the cox-2 protein was one of target of mir-143 and mir-143 could directly modulate the expression level of cox-2 in vivo. 21790228_4 the above findings were further confirmed that mir-143 significantly inhibits proliferation and migration by decreasing the level of cox-2. 25356105_3 mechanistically, we demonstrated that overexpression of mir-183 decreased, and inhibition of mir-183 increased the expression of pdcd4, a tumor suppressor, at both mrna and protein levels. 25356105_4 taken together, our results suggest that mir-183 may modulate progression and metastatic potential of gastric cancer through inhibition of pdcd4 expression. 23554480_1 we have demonstrated that ve-cadherin is a direct target of mir-101 using a luciferase reporter assay, which showed that mutated ve-cadherin 3'utr and mir-101 cotransfection did not change luciferase activity.we 23554480_2 have identified hiv-1 tat c-induced disruption of ve-cadherin mediated by mirna-101 in human brain microvascular endothelial cells . 23554480_3 hiv-1 tat c increased the expression of mir-101, which led to downregulation of ve-cadherin. 23554480_4 overexpression of mir-101 resulted into the suppression of ve-cadherin. 23554480_5 inhibition of mir-101 by the mirna inhibitor enhanced the expression of ve-cadherin. 26090866_1 using mirna-microarray and mechanistic studies, sb increased the expression of microrna-494 and both bmi1 and adam10 were identified as the novel targets of mir-494. 26090866_2 we identified bmi1 and adam10 as novel direct targets of mir-494, through which mir-494 mediates silibinin-dependent inhibition of hnc-tics. 26090866_3 these results identified a crucial mir-494 binding site on the 3'utr of bmi1 and adam10 to suppress its expression. 26090866_4 consistently, real-time rt-pcr and western blotting analysis showed that sb treatment of hnc-tics also suppressed the mrna and protein levels of bmi1 and adam10, which our data implicated as targets of mir-494 . in this study, we showed that mir-494 directly binds to the 3'utr regions of bmi1 and adam10 in hnc-tics , thus represses the tumorigenecity and tic properties such as sphere formation capability, cd44 and aldh1 expression, clonogenic ability, and in vivo tumor initiation incident . 18810376_1 overexpression of mir-128 suppressed a luciferase-reporter containing the e2f3a-3'utr and reduced the level of e2f3a protein in t98g cells. 18810376_3 when the hypothesized mir-128 binding site in the 3'-utr of e2f3a mrna was mutated, luciferase activity was restored close to the control level . 18810376_4 overexpression of mir-128 in t98g cells resulted in down-regulation of e2f3a at posttranscriptional level as assessed by western blot . 23173671_2 furthermore, sirna-mediated knockdown of mtor partially phenocopied the effect of mir-99a overexpression, suggesting that the tumor suppressive role of mir-99a may be mediated primarily through mtor regulation. 23173671_3 the enforced expression of mir-99a in rcc cell lines led to a decrease in mtor protein and also led to a decrease in phospho-mtor protein, compared with nc transfectants . 23173671_5 these findings showed a direct interaction between mir-99a and mtor mrna in rcc cell lines. 23173671_6 taken together, these findings showed a direct interaction between mir-99a and mtor mrna in rcc cell lines. 18700987_1 we used qrt-pcr to examine the mrna levels of 20 confirmed mir-17-5p target, 3 possible mir-17-5p target, and 7 other cell cycle related genes in hek293t cells with both transient and stable over-expression mir-17-5p. 20410487_1 in this study, we report that mir-466l can upregulate both mrna and protein expression of il-10 in tlr-triggered macrophages. 20410487_2 mir-466l upregulates il-10 expression of both mrna and protein levels in tlr-triggered macrophages. 20410487_3 further experiments confirmed the upregulation of il-10 by mir-466l in serum-starved 3ll cells . in conclusion, we demonstrate that mir-466l can upregulate il-10 expression in tlr-triggered macrophages by antagonizing rbp ttp-mediated il-10 mrna degradation, andtheworking model we proposed is shown in fig. 26482618_1 to verify whether akt3 is a direct target of mir-29a in ptc, a human akt3 3'-utr fragment containing the binding sites of mir-29a or the mutant sites was cloned into the pgl3 vector. 26482618_2 these results indicated that mir-29a can bind directly to akt3 and inhibits its expression. 26590574_1 in addition, mir-10a was found to target bcl6 and regulated its expression in transcription and translation levels. 26590574_2 these findings showed that mir-10a targeted to bcl6 and regulated its expression in transcription and translation levels. 26590574_3 finally, we identified bcl6 to be a target of mir-10a in patients with aml. 26540574_1 the above results demonstrated that jak1 and stat6 were the target genes of mir-23a, while irf4 and ppar-gamma were the target genes of mir-27a in m2 polarization. 26540574_2 mir-23a and mir-27a inhibit m2 polarization by targeting jak1/stat6 and irf4/ppar-gamma,respectively, through a negative feedback loop. 23928694_2 the expression of the stat3 regulator mir-124 was upregulated in deficiency conditions. 20609388_2 4, the levels of brn-3b, but not of brn-3a, are markedly reduced upon the co-transfection of mir-23 and mir-214, thus suggesting a direct effect of the micrornas on the 3'-utr of endogenous brn-3b. 20609388_3 furthermore, while mir-23 alone has no effect, endogenous brn-3b mrna levels are reduced following the transfection of mir 214 on its own. 20609388_4 this is likely due to a cooperative effect of the exogenously transfected mir-214 with endogenous mir-23. 25651400_1 these results suggest that stat5 is an important target gene of mir-204 in the b-cell lymphoma. 21646425_1 we show here that whereas dna methylation at the mct1 promoter is unlikely to be involved in cell-type-specific transcriptional repression, three micrornas , mir-29a, mir-29b, and mir-124, selectively targetboth human and mouse mct1 3' untranslated regions. 21646425_3 to test the combined effect of multiple mirnas on the mouse mct1 3- utr, mir-29a, mir-29b, and mir-124 were tested individually and together by luciferase assay . 21646425_5 overexpression of mir-124 produced a statistically significant decrease in the endogenous mct1 mrna level. 21646425_6 this confirms that mir-124 is able to targetnaturally occurring mct1 mrna and that this results in mrna degradation. 21646425_7 this suggests that mir-29a and mir-29b may targetmct1 at least partially through mrna degradation. 22967897_2 two anti-apoptotic genes, aeg-1 and bcl-2, are identified as targets of mir-136, and restoration of aeg-1 or bcl-2 expression suppresses mir-136-enhanced apoptosis. 22156303_2 the abca1 3'-utr harbors three closely spaced/overlapping predicted mir-33a/b target sites, and fusion of the abca1 3'-utr fragment containing these sites to a luciferase reporter confirmed that mir-33a/b can indeed regulate the abca1 3'utr through the mir-33 binding sites, as shown by site-directed mutagenesis . 22156303_3 taken together, the targeting of abca1 by mir-33a/b and the apparent cooperativity of mir-33 and srebp adds an elegant layer of regulation to the cholesterol homeostasis mechanism, and supports the idea that mir-33a/b may represent attractive therapeutic targets to raise hdl and ameliorate atherosclerosis. 21310851_1 taken together, these results indicated that hsa-mir-613 targeted lxralpha 3'-utr through 613mre. 21310851_2 having demonstrated that hsa-mir-613 targeted lxralpha, we were surprised to find that lxralpha can positively regulate the expression of hsa-mir-613. 21310851_3 fig.2 hsa-mir-613 negatively regulated the expression and activity of endogenous lxralpha. 26255635_1 we showed that mir-223 affected the expression of its target genes nfia and rhob, but also osteoclast marker genes and the akt signalling pathway, which induces osteoclastogenesis. 22387553_1 bcl6, socs1, and dusp10 are direct target of posttranscriptional regulation mediated by mir-30b, mir-155, and mir-21, respectively. 22387553_2 taken together, these data indicate that bcl6, socs1, and dusp10 are direct target of posttranscriptional regulation mediated by mir-30b, mir-155, and mir-21, respectively. 22387553_5 hairpin inhibitors of mir-30b induced upregulation of bcl6 and socs1, whereas inhibitors of mir-155 upregulated only socs1. 22387553_6 kd of mir-21 resulted in upregulation of dusp-10 yet had no effect on bcl6, which lacks the targetsequence for mir-21. 25330074_1 the effects of these mirnas in modulating mm cell apoptosis was also investigated; re-expression of mir-152, -10b-5p and mir-34c-3p mimics induced cleavage of parp- and caspase-9 and -3, compared to normal control-transfected cells.beta-transducin 25330074_2 repeat containing e3 ubiquitin protein ligase and myc binding protein , predicted targets of mir-10b-5p.in 25330074_3 addition, e2f3, btrc and mycbp were significantly increased after mir-10b-5p mimic transfection 26526790_1 it demonstrated that mir-193b directly targeted mcl-13 ' -utr . 26526790_2 hese results indicate that mcl-1 is negatively regulated by mir-193b as its direct target gene in mcf-7/doxr cells. 26112332_1 we found that the expression of bmp7 in mir-22-overexpressing hepg2 cells was significantly decreased, while the expression of bmp7 in mir-22-depleted hepg2 cells was significantly increased, as measured by rt-qpcr , and by elisa on either cellular protein or secreted protein . 26112332_3 these data suggest that mir-22 targets 3'utr of bmp7 mrna to inhibit its expression. 26201446_1 mir-504 can target many transcription factors, including nrf1. 26201446_2 we extracted total rna and the cne2-nc and cne2-mir-504 proteins at different time points and used rt-pcr and western blot to determine the mrna and protein level, respectively, of nrf1 .5c. the data revealed that the mrna expression level of nrf1 was only slightly down-regulated in cne2-mir-504 cells at different time points. 26201446_3 however, the protein expression level of nrf1 was substantially down-regulated in cne2-mir-504 cells. 26201446_4 results indicated that the protein expression level of nrf1 was obviously up-regulated in cne2-ir-anti-mir-504 cells, suggesting that inhibiting the expression of mir-504 can lead to up-regulation of the nrf1 protein level. 26201446_5 , we found that nrf1 has one mir-504 binding site at 506-513 of the 3'-utr, a position that is shared by many species, including humans .5e. we then constructed a nrf1-3'-utr plasmid that contains the putative mir-504 binding site and a nrf1-3'-utr-mut plasmid that has mutant sequences in the mir-504 binding site. 25190487_1 limk1 is a novel target of mir-138 in skov3 and ho-8910 cells 26172537_1 the bioinformatical screening of potential mirna targets identified bcl2 as a putative target for mir-148a-3p, mir-204-5p and mir-375 and dnmt3b for mir-148a-3p and mir-375. 26172537_3 an inverse correlation was observed for both of the predicted dnmt3b-targeting mirnas: mir-375 and mir-148a-3p. 26172537_4 a negative correlation was observed between bcl2 and mir-375, whereas no relationship was found between bcl2 and mir-148a-3p or bcl2 and mir-204-5p. 25683004_1 mir-10a targets the 3'-utr of epha8 transcripts and negatively regulates its expression. 25683004_2 mir-10a targets the 3'-utr of epha8 and down-regulates its expression. 26195221_1 mir-132 is upregulated by adrenergic activation and targets mecp2 for repression. 26770450_1 l1cam is a potential downstream target gene of mir-503 in glioma with a conserved mir-503-binding site in the 3'-utr of l1cam mrna. 26770450_2 these data suggest that l1cam may be a direct functional target of mir-503 in glioma. 26770450_3 the assay showed a negative regulatory effect of mir-503 on l1cam. 26770450_4 up-regulated mir-503 could decrease the expression of l1cam. 18713946_2 importantly, the mutant mir-26a responsive element was able to mitigate repression , therefore suggesting a direct regulation of ezh2 via mir-26a. 18713946_3 based on our hypothesis that mir-26a effects might be in part mediated via the deregulation of ezh2, we used shrnas to knock down the expression of ezh2 in bl cell lines. 18713946_4 in agreement with the mir-26a findings, we observed a significant decrease in cell numbers in transfected raji and namalwa cells with a pronounced effect at 96 hours after shrna induction and ezh2 down-regulation . 26151747_1 lats2 is one of the major targets of both mir-372 and mir-373, and contains two mir-372 and -373 pairing sites in its 3'-utr. 21472990_1 we report here the involvement of mir-146a and mir-146b-5p that bindto the same site in the 3'utr of brca1 and down-regulate its expression as demonstrated using reporter assays. 21472990_2 the expression of these mirnas individually or in combination led to a drastic reduction in the amount of irak1, a known target of mir-146a and mir-146b-5p , and in the amount of brca1 protein , demonstrating that mir-146a and mir-146b-5p are effective on the endogenous brca1 gene. 21472990_3 taken together, these results show that mir-146a and mir-146b-5p down-regulate the expression of the brca1 gene in hela cells. in the three basal-like cell lines with the highest mir-146a/b-5p expression level, the amount of brca1 was particularly low. 21472990_4 these results demonstrate that mir-146a and mir-146b-5p down-regulate the expression of wt and mutant alleles of the brca1 gene in mammary cell lines. 21472990_5 these results show that down-regulation of brca1 by mir-146a and mir-146b-5p impairs two cellular processes controlled by brca1. 26663087_1 in concordance with our in silico data, we found that the agomir to mir-874-3p repressed hdac1 expression, whereas the antagomir increased its expression . 26663087_2 this suggests that the in vivo anabolicaction of mir-874-3p is also mediated through hdac1 repression and runx2 activation. 26663087_3 we likewise propose a pathway in which mir-874-3p down-regulates hdac1 expression to enhance runx2 expression and osteoblast differentiation. 25912033_1 using the target prediction analysis, we found that a conserved sequence in the 3'-utr of klf11 mrna has a perfect match to the seed sequence of mir-30. 25912033_2 our results demonstrated that the mimics of mir-30 family members could significantly attenuate the luciferase activity of the wild type klf11 3'-utr reporter but not that with mutated mir-30-binding site. 25912033_3 as expected, a significant decrease of klf11 was observed in the mir-30 transfected cells, whereas the smad7 expression greatly increased as indicated by qrt-pcr . 25912033_4 the reverse experiment revealed that transfection of mir-30 antagomir resulted in a significant increase of klf11 and markedly suppression of smad7. 25912033_5 western blot also confirmed that mir-30 suppressed klf11 expression in hscs . 26512101_2 the tissue-preferential effect of rcf3 on mirna accumulation and activity was confirmed with rna isolated from 14-daysold vegetative apices, in which reduction in mature mirnas and corresponding overaccumulation of mirna-targeted mrnas was much more evident than in age-matched whole-plant samples . 26074357_1 the expression of slain1, cav2, erbb4, and edn1 was negatively correlated with that of mir-130a. 26074357_3 found that both mrna and protein levels of slain1 and cav2 were down-regulated by anectopic expression of mir-130a in pr20 cells. 26074357_4 we per-formed luciferase reporter assays to investigatewhether mir-130a directly binds to the 3'-utr of slain1 and cav2 mrnas. 26074357_5 these results indicated that mir-130a bound to the two target sites within the 3'-utr of slain1 mrna and negatively regulatedits protein expression in pr20 cells. 12573261_1 antisense transcripts at the emx2 locus in human and mouse conservation of functional human and murineemx2 antisense genes, of overlap between the sense and the antisense transcripts, and of identical cellular expression patterns suggests a biological function for emx2os, presumably to regulate emx2. in situ hybridization of mouseendometrial tissues at other estrous cycle stages produced similar results, with no appreciable difference in the cellular location of emx2 and emx2os . 12573261_2 these studies demonstrate that emx2 and emx2os and their murineorthologs have coincident cellular expression patterns in the endometrium. 19460962_1 conversely, inhibiting mir-92a by antagomir-92a treatment in mice increased the expression of itga5 mrna and protein in the vasculature of skeletal muscle tissue . 26743123_1 psen1 is a direct target of mir-193a-3p in oesophageal cancer cells. 26743123_2 figure 4. psen1 is a direct target of mir-193a-3p in escc cells. 26619802_1 mechanistic investigations defined that nuclear factor ya , a ccaat box-binding transcription factor, was a direct and functional downstream target of mir-140, which was involved in the malat1 knockdown induced regulation of btb function. 26619802_2 luciferase activity was significantly decreased in cells co-transfected with pre-mir-140 and nfya-3'-utr-wt, suggesting that nfya was a direct target of mir-140. 26619802_3 these results suggested that nfya was a direct target of mir-140 with the specific binding site. 26619802_4 mechanistic investigations defined nfya as a direct and functional downstream target of mir-140, which was involved in the malat1 knockdown induced regulation of the integrity and permeability of btb, as well as the expression of zo-1, occludin, and claudin-5. 21643012_1 thus, mir-27a negatively regulates igf-1 expression in ewing sarcoma. 21643012_2 as shown in figure 3f, compared with negative control, mir-100 robustly inhibited reporter expression through its predicted site in the igf-1r 3' utr, but had no effect when the mir seed sequence was mutated. 21643012_3 similarly, mir-125b specifically inhibited reporter activity through its predicted site in the rsk1 3' utr . 21643012_4 surprisingly, we were unable to demonstrate direct regulation of the igf-1 3' utr by mir-27a , suggesting that the regulation of igf-1 protein levels occurs via other mechanisms. 19962668_1 mir-221 and mir-222 directly targetpten and timp3 3'utrs. 19962668_2 conversely, when we performed luciferase assays by using a plasmid harboring the 3'-utr of pten and timp3 mrnas, where the binding sites for mir-221 and mir-222 were inactivated by site-directed mutagenesis, we observed a consistent reduction in mir-221&222 inhibitory effect . 19962668_3 moreover, we found, as assessed by western blot, an inverse correlation between mir-221&222 rna expression and pten and timp3 protein expression in most cell lines analyzed , confirmed also by qrt-pcr . 19962668_4 these data further support the finding that pten is a direct target of mir-221&222 also in vivo. 19962668_5 interestingly, we observed a significant increase on the migratory and invasive capabilities of h460 and sk-hep1 cells after mir-221&222 overexpression as well after pten and timp3 downregulation. 26116834_2 previous results showed that also in our model, mir-21 targets the 3'-utr of pten mrna. 26116834_3 real time pcr analysis demonstrated that the addition of curcumin, to cml cells, for 24 hours, caused a dose-dependent increase in pten mrna . 26116834_5 our data indicate that the curcumin treatment induces an exosomes-mediated decrease of mir-21 that in turn causes the modulation of pten expression in cml cells, confirmed by the study of gain and loss of function for mir-21. 26729197_1 thus, mir-31 could target itga5 mrna and negatively regulate its expression. 23175429_1 overexpression of mir-16-1 attenuated migration and invasion of glioma cells, and u251 cells transfected with mir-16-1 showed significantly lower endogenous mrna levels of zyxin than those transfected with nonspecific control mirna or mock . in summary, we demonstrated that mir-16-1 expression was markedly decreased in human glioma cell lines, and for the first time, described the roles of mir-16-1 in cellular proliferation, migration, and invasion abilities of high-invasive glioma cells, and suggested that zyxin may be one of putative target genes of mir-16-1. 17443681_1 3' untranslated regions of the genes and experimentally established kcnq1 and kcne1 as target for repression by muscle specifeid micrornas mir-133 and mir-1. 17443681_2 our experiments demonstrated that kcne1 is critically regulated by mir-1, but not by mir-133; mir-1 produced some 79% abrogation of the luciferase activity reported by the vectors carrying the 3'-utr of kcne1 and 70% reduction of kcne1 protein level . 17443681_4 the kcne1 mrna was unaffected by mir-1 . 22132820_1 as the binding site of rnd3 is conserved between human and mouse species, we sought to validate the regulation of rnd3 by mir-17 through a luciferase reporter assay that could verify the direct interaction between mir-17 and the rnd3 3'-utr. 22132820_2 overexpression of mir-17 reduced luciferase activity from the reporter vector containing the 3'-utr of rnd3 . 22132820_3 moreover, mutation of the putative binding site on the rnd3 3'-utr abrogated this repression, supporting the direct interaction of mir-17 with rnd3. 22132820_4 this result suggests that mir-17 may directly regulate the expression of endogenous rnd3. 22132820_5 this result confirmed that rnd3 mediated the effect of mir-17 on promoting cell proliferation and cell cycle progression. 26800397_1 ppp2r2a is a known target of mir-222 in hepatocellular cancer cells 4. we observed that mir-222 overexpression significantly down-恟egulated ppp2r2a expression, whereas knock-恉own of endogenous mir-222 up-恟egulated the ppp2r2a level . 26800397_2 data from the dual luciferase assay showed that mir-222 decreased the luciferase activity of wild-恡ype pmir-怭pp2r2a-3'-utr but not that of the mutated pmir-怭pp2r2a-3'-utr . 26800397_3 hese results indicated that ppp2r2a was a direct target of mir-222 in bladder cancer cells in a manner associated with mir-222-恑nduced proliferation. 25876455_1 therefore, we hypothesized that downregulation of mir-27a might play a role in mediating tlr4-mediated secondary inflammatory damage after ir by up-regulating the ticam-2 transcript. 25876455_2 these results are consistent with the hypothesis that the ir-mediated reduction in mir-27a down-regulates ticam-2 expression, which in turn influences tlr4 signaling and the activation of downstream inflammatory cytokines. 24065131_1 in contrast, ryhb pairing to cira mrna promotes changes in rna structure that displace hfq, thereby allowing efficient translation as well as mrna stabilization. 26275944_1 meantime, luciferase reporter assays identified zeb1 as a direct target of mir-205 in eoc cells. 26275944_2 mir-205, acting as an oncogenic mirna, may promote the clinical progression of eoc patients and enhance the cellular motility in vitro by directly and negatively regulating zeb1, providing a potential therapeutic strategy for suppression of eoc metastasis. in addition, we confirmed that mir-205 could directly and negatively regulate zeb1 in eoc cells, the evidence for which were from the following sources: , the endogenous mir-205 level was higher, whereas zeb1 level was lower in eoc cells and tissue samples, indicating the inverse correlation of them; ,the alteration of mir-205 expression in eoc cells resulted intheopposite change of zeb1 expression, highlighting their negatively regulation; and , zeb1 mrna 3'-utr could bear a binding site of mir-205. 25906693_1 we also revealed that jund is a target of mir-494. 25906693_2 western blotting analysis demonstrated that treatment with the lentiviral antigomir-494 vector resulted in increased expression of jund and decreased expression of cytochrome c . 21402938_1 examination of the sequence of the orf56/primase 3'utr with several mirna target prediction programs suggested two likely targets for mir-k5jone in exon 1 of the orf57 gene, and one in exon 2 of the gene. 21402938_2 the sequences of these target sites, and their predicted basepairing with mir-k5, are shown in fig. 22844247_2 let-7b and let-7c directly downregulate ksrp mrna during pituitary development. 21149267_1 here, we show the 3'-utr of cd44 is able to antagonize cytoplasmic mirnas, and result in the increased translation of cd44 and downstream targetmrna, cdc42. 21149267_2 computational algorithms have predicted three mirnas, mir-216a, mir-330 and mir-608, can bindto both the cd44 and cdc42 3'-utrs. 26851511_3 these results suggested that mir-18a/b could target 3 ' utr of igf-1 by complementary base-pairing to its target site, as predicted. 26851511_4 these results further supported the idea that igf-1 was a downstream target of mir-18b during hrecs proliferation. 26818663_1 transfection of intestinal cells with a mir-7 mimic or inhibitor confirmed its negative regulatory effect on rnf183 expression and ubiquitination of i魏balpha. 26818663_2 conversely, the mir-7 inhibitor significantly up-regulated the expression of rnf183, suggesting that mir-7 may be a direct regulator of rnf183 at both the transcriptional and translational levels. 26818663_3 we further determined that mir-7 is a negative regulator of rnf183 through direct interaction with the 3'-utr of rnf183 to inhibit its translation. 20159450_1 we identified nmda receptor subunit nr2a as a target of mir-125b and show that nr2a mrna is specifically associated with fmrp in brain. 20159450_2 together these data indicate that neuronal mir-125 can specifically regulate nr2a reporter expression. 20159450_3 these data extend the findings using ff-luc reporters and demonstrate that mir-125b specifically regulates endogenous nr2a in neurons. 20159450_4 together these data indicate that endogenous mir-125 directly and specifically regulates nr2a expression and affects nmda receptor function accordingly. 20159450_5 together these data indicate that the 3'-utr of nr2a is normally suppressed by fmrp and ago1 as well as by mir-125, and these mechanisms show partial functional interaction. 20219912_1 here, we report that cellular mrnas encoding the cellular cyclin-dependent kinase inhibitor p21, a key inducer of cell cycle arrest, are direct targets for kshv mir-k1. 20219912_2 ectopically expressed kshv mir-k1 specifically inhibited the expression of endogenous p21 in kshv-negative cells and strongly attenuated the cell cycle arrest that normally occurs upon p53 activation. 20698883_1 il6r is a candidate target of mir-23a. 20698883_2 three binding sites of mir-23a were found in the 3'utr of il6r mrna. 20698883_3 these observations suggest that mir-23a bindainly to the first targeting site of the il6r mrna 3- utr and represses gene expression. 20698883_4 these data highlight the prediction that il6r is a direct target of mir-23a. 20698883_5 figure 5b shows that, compared with normal tissue samples, il6r mrna was consistently downregulated in gastric cancer tissue samples. in addition, knockdown or overexpression of mir-23a also enhanced or decreased il6r protein expression, respectively . 20698883_6 this suggests that mir-23a promotes mgc803 cell growth by negatively regulating il6r. 21149577_2 the human tr-beta1 mrna was predicted to have other binding sites for mir-27a, and the luciferase activity of a human tr-beta1 3- utr reporter was decreased significantly by mir-27a . 21149577_3 these findings suggested that the binding sites of mir-27a in the 3- utr of tr-beta1 could mediate translational repression by mir-27a. 21149577_4 these findings indicated that tr-beta1 is a target of mir-27a both in rat and human cells. 21149577_5 because mir-27a could upregulate the -beta-mhc gene under serum-containing conditions, these results indicated that the upregulation of -beta-mhc by mir-27a resulted mainly from the downregulation of tr-beta1 rather than rxralpha. 21149577_6 these findings suggested that the upregulation of mir-27a could increase -beta-mhc mrna levels via tr-beta1 but did not affect cardiac cell differentiation in mousees cells. 21149577_7 as a result, during heart development, mir-27a and tr-beta1 mrna levels increased continuously while -beta-mhc levels decreased . 26707794_1 adamts5 gene 3'-utr carries a putative hsa-mir-15a binding site and is negatively regulated by hsa-mir-15a. 26707794_2 the results revealed that a binding site for hsa-mir-15a was in the adamts5 mrna 3'-utr . 26707794_3 these results suggest that hsa-mir-15a binds directly to the 3'-utr of adamts5 mrna and inhibits gene expression. 26707794_4 these results also indicate that adamts5 is a direct target of hsa-mir-15a. 26370615_1 in addition, as determined by luciferase assays and western blotting, smad2, a crucial mediator of pulmonary fibrosis, was identified to be one of target genes of mir-486-5p. in fibroblasts, smad2, a critical mediator of multiple fibrogenic associated-processes, including cell proliferation, migration, invasion and differentiation into myofibroblasts, was identified to be a target gene of mir-486-5p. 26370615_2 these results support the hypothesis that mir-486-5p exerts its anti-fibrotic effects by suppressing collagen synthesis and targeting smad2 directly. 21593139_1 here, we show that the 3'-utr of sec23a mrna is indeed a targetfor mir-375 and mir-200c and that both mirnas downregulate sec23a protein expression when ectopically expressed in human 293t cells. 21593139_2 taken together, these results show that the sec23a 3'-utr is an independent targetfor both mir-200c and mir-375. 21593139_3 figure 1. sec23a mrna is a targetfor mirnas mir-200c and mir-375. 21593139_4 taken together, our data establish sec23a as a targetfor both mir-200c and mir-375 in vitro. 22024478_1 we validate that mir-124 may suppress the expression of ahr by targeting its 3'-utr. 22024478_3 the mrna and protein expression level of ahr was inhibited by pre and elevated by inh. the results showed that mir-124 indeed regulated expression of ahr by directly targeting its 3'-utr. 22024478_4 the results show that the expressions mir-124 and ahr are complementary in clinic and suggest that mir-124 might negatively regulate the expression of ahr in neuroblastoma cells not only in vitro but also in vivo. 22024478_5 these studies support our findings that inhibition of mir-124 caused increasing in ahr and resulted in cell differentiation. 21520166_3 further studies showed that mir-1 was able to enhance the hbv core promoter transcription activity by augmenting farnesoid x receptor alpha expression. in addition, mir-1 arrested the cell cycle at the g phase and inhibited cell proliferation by targeting histone deacetylase 4 and e2f transcription factor 5. 23824072_1 in lymphocytes, c-myb was a direct target of mir-150. in cardiac myocytes, we found that c-myb was also involved in mir-150-mediated h2o2-induced cardiac cell death. 23824072_2 these results suggested that c-myb may be a target gene of mir-150 in cardiac myocytes. 25277326_2 lin28b and nras were targeted by mir-4500. 26450995_1 cited2 was the target of mir-200b and was downregulated by high glucose. 26450995_2 two mir-200b binding sites in the 3'-untranslated region of the cited2 mrna were required for inhibiting cited2 expression. 26450995_3 these results strongly suggest that mir-200b directly interacts with the cited2 mrna and forms the mir-200b/cited2-mrna complex. 26450995_4 altogether, these results indicate that mir-200b interacts with cited2 mrna via the specific binding sites located in its 3'-utr, and, thus, silencing cited2 expression by degrading mrna and blocking translation. 26619149_2 finally, if phactr4 is a bona fide mir-21 target, its levels should be de-repressed in our crispr/cas-edited isogenic scc line that specifically lacked mir-21 . 26619149_3 by exploiting the tcga database and applying both crispr/cas and rapid lentiviral-based genetics to skin and head and neck epithelia in mice, we verified the mir-21-independent tumorigenic activity of mir-21 and uncovered phactr4 as a key target whose suppression confers much of the oncogenic activity of this hitherto ignored mirna. 26081980_1 the luciferase reporter assay showed that mir-4649-3p directly targeted shp-1 by binding to the 3'-untranslated region of shp-1 mrna. in conclusion, mir-4649-3p inhibits cell proliferation by targeting shp-1 in npc cells. 26081980_2 the luciferase reporter assay indicated that mir-4649-3p suppressed shp-1 expression by binding to shp-1 3'utr and inhibiting shp-1 mrna translation. 24681041_1 further, we showed that mir-216b could directly target a specific fragment in the 3' untranslated region of beclin 1 as demonstrated by luciferase assay, and consequently decreased the expression of beclin 1. consistently, knocking down beclin 1 significantly decreased hcpt-triggered autophagy and apoptosis, and increased the viability of htfs treated with hcpt, 22431396_3 from in silico analysis and validation experiments, foxo1 was identified as the target of mir-182, and restoration of foxo1 expression in mir-182-overexpressing osteoblasts rescued them from the inhibitory effects of mir-182. 22431396_4 here, we identified one additional crucial mirna, mir-182, which regulates osteoblastogenesis by repressing foxo1 and thereby negatively affecting osteogenesis. 22431396_5 fig. 5. mir-182 target the foxo1 3'utr. 22431396_6 schematic of the mir-182 putative targetsite in the mouse foxo1 3' untranslated region and alignment of mir-182 with the foxo1 3'utr showing complementary pairing.sequences 22431396_8 foxo1 expression in c3h10t1/2 mesenchymal stem cells and mc3t3e1 preosteoblasts after transfection with mir-182. 26877261_1 within the notch and wnt clusters specifically, four genes were found to contain predicted mir-375 binding sites. 26877261_2 mir-375 overexpression in variant cell lines resulted in decreased protein expression of both notch2 and rbpj . 26877261_3 furthermore, knockdown of mir-375 in the classic cell line mkl-1 resulted in increased rbpj expression. 26877261_4 the proximal notch2 3' utr contains a highly conserved mir-375 binding site, whereas the 3' utr of rbpj features a poorly conserved binding site. 26877261_5 taken together, our data suggest that mir-375 negatively regulates the notch pathway via direct interactions with the 3' utrs of rbpj and notch2. 20548334_1 jak2 is a mir-375 target overexpression of mir-375 in ags and mgc-803 cells greatly reduced the protein level of jak2, whereas the level of jak2 mrna was not significantly affected , suggesting that mir-375 may suppress jak2 gene expression through translational repression. 20548334_2 these data suggest that mir-375 may inhibit jak2 protein expression through 3'-utr at the posttranscriptional level. 20548334_3 taken together, these results are consistent with our hypothesis that mir-375 may inhibit gastric cancer cell proliferation potentially by regulating jak2 expression. 23180826_1 three mirnas, mir-133a, mir-431, and mir-199a*, could bind to fibronectin. 21435193_1 over-expression of mir-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting brn2 translation. 21435193_2 this increase was not observed upon transfection of a scrambled control lna , suggesting that endogenous mir-211 represses brn2 levels in melanocytic cells. 21435193_3 together, this set of experiments suggest thatthe decrease in brn2 protein levels with mir-211 overexpression is because of direct targeting of brn2 translation by mir-211. 21435193_4 figure 3. the brn2 3'utr is a direct target of mir-211. 24252910_1 hsa-let-7g mirna targets caspase-3 and inhibits the apoptosis induced by ox-ldl in endothelial cells. 25301739_1 taken together, data indicate mir-200b directly repressing vegf-a protein expression via binding to 3'-utr of human vegf-a gene 25486906_1 here, we show that in repeatedly activated murine th1 cells, twist1 and t-bet induce expression of microrna-148a . 25486906_2 mir-148a regulates expression of the proapoptotic gene bim, resulting in a decreased bim/bcl2 ratio. 25486906_4 knockdown of bim expression by sirna in mir-148a antagomir-treated cells restores viability of the th1 cells, demonstrating that mir-148a controls survival by regulating bim expression. 22249254_1 levels of microrna -210 and mir-155 transcripts, which targetship-1, were increased in cd34 mds cells compared with their normal counterparts. 22249254_2 mir-155 has recently been shown to suppress ship-1 expression by binding to its 3' untranslated region . 22249254_3 these studies demonstrate that mir-155 and mir-210 are overexpressed in late-stage mds and that, similar to the effects recently shown for mir-155 , mir-210 downregulates ship-1 expression in myeloid cells. 22249254_4 figure 4 mir-210 controls ship-1 expression. 22249254_5 mir-210 binds the 3' utr of ship-1 mrna. 22249254_6 figure 3 absence of ship-1 is associated with mir-210 and mir-155. 26561465_1 interestingly, a putative conserved binding site for mir-150 was found in the 3'-utr of igf2bp1 at 3321- 3328 bp . 26561465_2 luciferase reporter assay further confirmed that the mir-150 had an obvious inhibitory effect on the wild-type but not the mutant 3'-utr of igf2bp1 luciferase activity. 26561465_3 we consistently found that overexpression of mir-150 could obviously decrease the expression of endogenous igf2bp1 at the mrna and protein levels in mg63 cells. 26561465_4 these results indicate that mir-150 directly binds to the 3'-utr of igf2bp1 to regulate its expression. 21813606_1 subsequent quantitative pcr analyses of these splenic b cells revealed that c/ebpbeta, a transcriptional regulator of interleukin-6 that is linked to b-cell lymphoproliferative disorders, is downregulated when either mir-k12-11 or mir-155 is ectopically expressed. 23188671_1 these data demonstrate that mir-153 is a novel regulator of emt by targeting snai1 and zeb2 and indicate its potential therapeutic value for reducing cancer metastasis. 23188671_2 these data indicate that mir-153 regulates snai1 and zeb2 expression through targeting their 3'-utrs that are complementary to the seed region of mir-153. 23188671_3 collectively, the present study revealed a critical inhibitory effect of mir-153 on metastasis via regulation of emt by way of targeting zeb2 and snai1. 23188671_4 fig.4.mir-153 targeted snai1 and zeb2. 25485521_1 our data demonstrate that mir-20a reduce autophagy by targeting 3'-utr of atg16l1 and osteoclast differentiation.mir-20a 21221794_1 epigenetic silencing of mir-137 induced an up-regulation of its target, cdc42. 21221794_2 the relative luciferase activity of the wt construct of cdc42 3'utr in both the gastric cancer cells was significantly reduced in the presence of mir-137 , whereas such a suppressive effect of mir-137 on luciferase activity was not observed in both cells with the mut construct of cdc42 3' utr , highlighting a direct and specific interaction of mir-137 on cdc42 3' utr. 21221794_3 together, these data indicate that cdc42 is a targetfor mir-137 in ags cells. 21221794_4 these findings also suggest that inactivation of cdc42 is involved in mir-137-induced apoptosis. 26052033_2 since the four mir-196a target genes were significantly upregulated in silenced mir-196a net cells, we explored the potential downstream genes of the four direct target genes hoxa9, hoxb7, lrp4 and rspo3. 21820330_1 mir-29-mediated repression of ifn-gamma involves regulation of both t-bet and eomes. 21820330_2 these results demonstrate that both the tbx21 and eomes 3'-utrs are directly responsive to mir-29 and that physiological expression of mir-29 in wild-type helper t cells is sufficient to mediate these effects. 21820330_3 although we must acknowledge that additional mir-29 targets may also contribute, we conclude that mir-29 regulates ifn-gamma production by simultaneously targeting t-bet and eomes, two proteins with overlapping transcriptional activity. 26252186_1 suggesting that the fzd7 mrna, rather than fzd1 and fzd8 mrnas, is a potential target of mir-222. 26252186_2 these results indicate that mir-222 interacts with the fzd7 mrna via its cr, thus repressing fzd7 translation. 25980823_1 by targeting of the smad2-3 ' -utr, mir-148a blocked the expression/activation of smad2, and in turn, restored the epithelial characteristics, adhesive abilities, and csc-like properties. 25980823_2 these results suggested that upregulation of mir-148a by gla contributed to suppression of endogenous smad2 in breast cancer cells. in our present study, gla attenuated the endogenous smad2 via upregulation of mir-148a expression. 19221490_1 the mir-34 family regulates cell cycle progression, cellular senescence and apoptosis, but the targets of mir-34 are not completely defined. 19221490_3 sirt1 also regulates p53 dependent apoptosis through deacetylating and stabilizing p53. 19221490_4 we also discovered that sirt1 mediates mir-34a activation of apoptosis by regulating p53 activity. 19221490_5 based on this observation, we propose a positive feedback loop, in which p53 induces expression of mir-34a which suppresses sirt1, increasing p53 activity. 26695693_1 mir-1914* and -1915 interacted with the 3- -untranslated region of nfix and reduced nfix its level in chemoresistant crc cells. 26695693_2 plasma mir-1914* and -1915 interact with nfix rna and reduce its level in chemoresistant crc cells to first-line chemotherapy. 26695693_3 we showed that mir-1914*+mir-1915 suppress crc cell chemoresistance by targeting nfix expression. 21175813_1 among them, mir-29a showed a positive therapeutic effect in liver cancer cells by inhibiting cell growth and inducing cell apoptosis, and ppm1d was confirmed to be the target gene of mir-29a. 21310411_1 ets-1 mrna was downregulated markedly when siets-1 was introduced into huvecs but remained stable in mir-155 or mir-221/222 overexpressed huvecs. in summary, the present study demonstrated that endothelial cells highly express mirnas, including mir-155 and mir-221/222. 21310411_3 fig. 2. ets-1 is a target of both mir-155 and mir-221/222. 25678279_1 furthermore, over-expression of mir-29c effectively reduced birc2 mrna and protein levels, increased infarct volume and apoptosis, and deteriorated neurological outcomes, whereas down-regulation played a neuroprotective role. 15722536_1 in the study reported here, nef-derived mirnas in hiv-1-infected and nef transduced cells were identified, and showed that hiv-1 transcription was suppressed by nef-expressing mirna, mir-n367, in human t cells. 17911266_1 ebv-encoded bart mirnas target the 3 utr of the lmp1 gene and negatively regulate lmp1 protein expression. 17911266_2 four mirnas were examined that lmp1 gene was a target of bart mirnas. 21118818_1 in addition, we found that the sr-family splicing factor sfrs1 is a target for mir-10a -and -10b in hela and sh-sy5y neuroblastoma cells. 21118818_2 the discovery of sfrs1 as direct target of mir-10a and -10b supports the emerging functional interaction between two post-transcriptional mechanisms, micrornas and splicing, in the neuronal differentiation context. in addition we could determine that the sr-family splicing factor sfrs1 is a target for mir-10a and -10b action, and we show that changes in mir-10a and -10b expression levels may influence cellular processes in which sfrs1 is involved. 20843712_2 lasp1 might have an oncogenical function in bc, and mir-1, mir-133a, and mir-218 might function as tumor suppressors through repression of lasp1 in bc. 20843712_3 we have demonstrated a strategy to address the mechanisms of cancer development through functional mirnas in bc. the expression levels of lasp1 mrna were significantly decreased in mir-1, mir-218, mir-133a, and mir-145 transfectants compared with the control transfectant , and the protein expression was markedly decreased in the transfectants . 20843712_4 this data suggests that mir-1, mir-218, and mir-133a reduce lasp1 expression through cleavage or translational inhibition. 18201269_1 we demonstrated that overexpression of mir-138 induced a reduction in htert protein expression, and confirmed targetspecificity between mir-138 and the htert 3-untranslated region by luciferase reporter assay. 18201269_2 we then examined whether mir-138 induction was able to repress htert protein expression. 18201269_3 hek-293 cells were transfected with mir-138 precursor molecules, which were designed to directly enter the mirna-processing pathway and mimic endogenous mir-138 in the cells. 18201269_4 overexpression of mir-138 induced a reduction in the htert protein level , but did not affect htert mrna expression . 18201269_5 to further confirm targetspecificity between mir-138 and htert, we carried out a luciferase reporter assay using a vector containing the putative htert utr targetsite downstream of a luciferase reporter gene. 18201269_6 base pairing between mir-138 and the wild-type or mutant putative targetsite is shown in figure 3c. the luciferase activity of hek-293 cells transfected with wild-type htert was significantly lower than that of cells transfected with mutant htert . 18201269_7 these data suggest that the htert gene is one of the target of mir-138, and that mir-138 can downregulate htert protein expression by post-transcriptional repression. 20020497_1 as seen on reporter assaying, mir-212 repressed the construct with the mecp2 3'-utr. 20020497_2 thus, we confirmed that 2 gc and 293t cell lines contained the binding site for mir-212 in the 3'-utr of mecp2 by end-point rt-pcr . 20020497_3 statistically significant repression of luciferase activity was observed in 293t cells cotransfected with pre-mir-212 precursor molecule and a reporter vector containing the mecp2 3'-utr targetsite . 20020497_4 these results demonstrated that mir-212 did not affect mrna stability, but downregulated mecp2 expression by blocking mrna translation. 10049768_4 semiquantitative pcr suggests that the stoichiometry between smad5 and dams transcripts ranges between 15 and 120 in normal and malignant hematopoietic cells. 10049768_5 the findings raise the possibility that dams may be a fail-safe mechanism for precise regulation of smad5 transcript levels that may be critical in maintaining normal homeostasis. 21874119_1 full-length anril was shown to repress p15ink4b expression. 21874119_2 induction of p15ink4b and p16ink4a by oncogenic ras was found to repress anril expression. 24583285_1 the results showed that mir-17-92 mirna expression was significantly increased and bim was decreased in tgctwh3-infected cells. 22396777_1 western blot and luciferase assay identified bdnf as a direct target of mir-376b-5p. 22396777_2 these results suggest that bdnf is a target gene of mir-376b-5p. 22396777_3 taken together, these data prove that mir-376b-5p directly inhibits bdnf expression. 22396777_4 our western blot analysis and luciferase assay experiments demonstrated that mir-376b-5p could directly bind to bdnf gene and inhibit its expression, providing support for our hypothesis that mir-376b-5p promotes myocardial ischemia injury possibly via the downregulation of bdnf. 25477374_1 primary transcripts and mature mir-143 and mir-145 were quantified by real-time pcr, putative targets were measured by western blotting.putative 25477374_2 targets of these mirnas were assessed following transfection with mir-143 or mir-145. in agreement with increased expression of mir-143 and mir-145 in proximal colon, predicted targets of these mirnas, apoptosis inhibitor 5 , erk5, k-ras, and insulin receptor substrate 1 , which are cell cycle and survival regulators, were expressed at a lower level in proximal than distal colon. 25477374_3 transfection of hca-7 colon cancer cells with mir-145 downregulated irs-1, and transfection of ht-29 colon cancer cells with mir-143 decreased k-ras and erk5 expression. in conclusion, mir-143 and mir-145 and the predicted target proteins api5, erk5, k-ras, and irs-1 display regional differences in expression in the colon. 25472588_1 finally, we identified ezh2 as the functional downstream target of mir-32 by directly targeting the 3'-utr of ezh2. 25472588_3 these data indicate that ezh2 is a direct target of mir-32 in oscc. 24345332_1 a reporter gene assay demonstrated that the binding sequences of mir-30d in the beclin 1-3' utr was the region required for the inhibition of beclin 1 expression by this mirna. 26885689_1 in the mechanistic study, we identified grb2 as a direct target of mir-329 in pancreatic cancer cells, and expression of grb2 was inversely correlated with mir-329 expression in pancreatic cancer patients. 26885689_2 figure 6: mir-329 directly targeted the 3'-utr of grb2 and inhibited grb2/ perk pathway. 26885689_3 these results suggest that grb2 is a major molecule targeted by mir-329, but additional mechanism is also involved. 25545366_1 taken together, our results demonstrated that mir-1470 directly recognized and bound to the 3'-utr of the c-jun mrna transcript to inhibit its expression. 22854828_1 we confirmed that predicted mir-30e and -181d target sites in htra1-3- utr are critical for repression of htra1 expression by introducing point mutations that disrupt the base-pairing of both predicted target sites into rluc-htra1-3'-utr construct . 22854828_2 mir-30e and mir-181d were identified as posttranscriptional negative regulators of htra1 by binding to its 3' untranslated region. 22854828_3 in vivo overexpression of mir-30e and mir-181d in dicer forebrain rescued rg proliferation defects. 25471065_1 indeed, we demonstrated that the ?p110α is a direct target of ?mir-378 in the liver, which would explain why the mice with hepatic ?mir-378 overexpression exhibited all of the hallmarks of impaired hepatic insulin signalling. 19897480_1 mir-155 could no longer decrease the luciferase activity of only the psicheck/155mut1,2-transfected cells , suggesting that mir-155 can interfere with luciferase expression via direct interaction with both mir-155 recognition sites harbored within the mecp2 3'-utr. 19897480_2 collectively, these results strongly support the hypothesis that mecp2 mrna is a target of both mir-155 and -802 and suggest that these mirnas markedly decrease mecp2 expression by targeting mecp2 mrnas for degradation. 19897480_3 taken together, these results further support the premise that mecp2 mrna is a targetfor mir-155 and -802 and underexpression of mecp2 may be involved, in part, in mediating ds. as mir-155 and -802 were overexpressed in the ts65dn and human ds brain specimens, we hypothesized that mecp2 and creb1 would be underexpressed and mef2c would be overexpressed in these mice, similar to what was observed in human brain samples. 22610076_1 we further demonstrated that mir-181a and mir-181b inhibiting bcl-2, mcl-1 and x-linked inhibitor of apoptosis protein by direct binding to 3'utr. 22610076_2 mir-181 acts directly at the bcl-2/mcl-1/xiap-3'utr. 22610076_3 thus, mir-181a and mir-181b directly inhibit the expression of bcl-2, mcl-1 and xiap by binding to the target sequence. 20610637_1 furthermore, in mcf7 cells, overexpression of mir-214 markedly decreased lactoferrin expression , and inhibition of endogenous mir-214 expression increased lactoferrin expression and cellular apoptotic activities 26158200_1 these results indicated that mir-214 bound to the sequence present in the 3'-utr of rat mpd in order to suppress the expression of mpd. 26158200_2 these results suggested that mpd mrna levels in the livers of shrsp were partially reduced by an increase in mir-214 levels. 17234972_2 overexpression experiments showed that mir-1 inhibited its in silico-predicted, growth-related targets, including ras gtpase-activating protein , cyclin-dependent kinase 9 , fibronectin, and ras homolog enriched in brain , in addition to protein synthesis and cell size. 26581909_1 we searched several databases to seek the possible downstream target genes of mir-15a-5p, including miranda and targetscan. in order to confirm the direct targeting of mir-15a-5p on bdnf gene, we carried out a dual-luciferase reporter assay. 26581909_2 it showed that mir-15a-5p significantly decreased the luciferase activity of wild type bdnf. 26581909_3 the result of western blot showed that mir-15a-5p overexpression also suppressed bdnf protein production in hepg2 and snu-182 cells. 25374061_1 the expression of endogenous ret was found to be upregulated by mir-218, and sirna-induced ret downregulation resulted in phosphatase and tensin homolog deleted on chromosome 10 upregulation and reversal of the inhibitory effect of mir-218 upregulation on hcc proliferation. 25374061_2 ret is targeted by mir-218 in hcc. 25374061_3 we also showed that ret was directly involved in the regulation of mir-218 on hcc development, possibly through pten signaling pathway. 18602365_1 mir-126 alters lung cancer cell phenotype by inhibiting adhesion, migration, and invasion and the effects on invasion may be partially mediated through crk regulation. 18602365_2 herein, we identify that crk may be a functional targetfor mir-126 in nsclc. 18602365_3 we did not observe a direct inverse correlation between mir-126 and crk in most cell lines or tissue. 2130430_1 tagln2 as a direct targetfor both mir-1 and mir-133a in rcc. 24861464_1 mir-302a and mir-4448 were markedly upregulated by treatment with saha and dznep, respectively. 24861464_2 dyrk1a, cdk2, bmi-1 and girdin, which are targets of mir-1246, mir-302a and mir-4448, were suppressed by treatment with saha and dznep, leading to apoptosis, cell cycle arrest and reduced migration of ags and hepg2 cells. 20869435_1 the 3- utr sequences of bothraldh2 and rxrab contain 9- and 7-mer sites, respectively, that are complementary to 5- nucleotides of mir-143 . 20869435_2 when assayed in cos7 cells, mir-143 repressed the luciferase activities of reporters containing these utr sequences . 19839716_1 these findings establish the tumor suppressive role of mir-205, which is probably through direct targeting of oncogenes such as erbb3 and zeb1. 19839716_2 through luciferase reporter assay, western blot and immunofluorescent staining, we identified that erbb3 and vegfa are direct target of mir-205 in breast cancer cell lines. 26707142_1 taken together, our results suggest that mir-148a can suppress the migration and invasion of breast cancer cells by targeting wnt-1 and inhibiting wnt/-beta-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis. 26417068_1 using both in vitro and in vivo analyses, we identified fzd4 and lrp6 as targets of mir-19a/b. 26417068_3 we demonstrate that mir-19a negatively regulates fzd4, its coreceptor lrp6, and wnt signaling, and that antagonism of mir-19a/b in aged mice improves blood flow recovery after ischemia and reduces repression of these targets. 26417068_4 given that loss of the cluster increased lrp6 protein levels and that mir-19a reduced luciferase activity of the 3- utr construct in a sequence-specific manner but did not directly reduce lrp6 mrna levels, it is likely that mir-19 regulates the translational efficiency of lrp6. 26417068_5 thus, suppression of mir- 19a/b activity regulates arteriogenesis and blood flow recovery, in part through enhanced fzd4 and lrp6 levels. 20010955_1 decreased mir-132 expression correlates with increased mecp2 protein, but no change in mecp2 mrna, in preconditioned mousecortex. 20010955_2 these studies validate that mir-132, an mirna known to regulate mecp2 protein expression, is decreased in preconditioned mousecortex. 26840408_1 to our knowledge, our study is the first to show that the level of nur77 is regulated by mir-124 and that nur77 has roles in proliferation of pediatric cancer cells such as daoy medulloblastoma cells. 26840408_2 we found that mir-124 was one of the 3 mirnas that substantially downregulated nur77 . 26840408_3 when we mutated the binding sites within the 3'utr corresponding to seed regions for mir-124, mir-15a, and mir-224, the mutated 3'utr became resistant to the corresponding mirna , demonstrating that these mirnas directly target nur77 by binding to a seed region within the nur77 3'utr. in this study, we found that mir-124 directly targets nur77 and that nur77 is upregulated in multiple pediatric cancer cell lines, including rhabdomyosarcoma, neuroblastoma, and medulloblastoma cell lines. 21112327_1 here, we show that microrna-124, a small non-coding rna down-regulated in oscc, is able to downregulate expression of integrin beta-1 by interacting with its 3' untranslated region. 21112327_2 having established that mir-124 is able to directly inhibit itgb1, we next sought to identify the sites of interaction in the itgb1 3' utr. 21112327_3 fig. 2. mir-124 downregulates itgb1 protein and mrna expression in oscc in culture. 21112327_4 over-expression of mir-124 in h357 significantly inhibited adhesion to fibronectin and reduced itgb1 expression suggesting this is a result of mir-124-mediated down-regulation of itgb1. in conclusion we have demonstrated, for the first time, the ability of mir-124 to suppress oscc invasion and migration by downregulating itgb1 expression. 21823019_1 moreover, bak1 was a direct target of mir-125b, and down-regulation of bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin. 21823019_2 our study indicates that mir-125b has a significantly promoting effect on chemoresistance of c13* cells and up-regulation of mir-125b expression contributes to cisplatin resistance through suppression of bak1 expression. 21823019_3 however, no inhibitory effect of mir-125b on the activity of the reporter with the mutant 3'-utr of bak1 was detected , indicating that bak1 mrna is a direct target of mir-125b. 21823019_4 fig. 3 bak1 as a direct target of mir-125b. 22439757_1 hoxa10 is a targetgene for mir-135a in breast cancer cells and overexpression of hoxa10 can partially reverse the mir-135a invasive phenotype. 22439757_2 mirna-135a promotes breast cancer cell migration and invasion by targeting hoxa10. 22439757_4 our results also suggested that mir-135a post-transcriptional down-regulation of the hoxa10 targetgene was not restricted to translation repression but also occurred by inducing mrna degradation ,4c, which agrees with previous reports on the action of mirnas and highly homologous target . 23097457_1 we found that erk-dependent latent viral gene expression, the induction of promigratory factors, and cell invasiveness followingde novoinfection of primary human endothelial cells are in part dependent on kshv suppression of dusp1 expression duringde novoinfection.kshv-encoded 23097457_2 mir-k12-11 upregulates the expression of xct , and existing data indicate a role for xct in the regulation of 14-3-3 , a transcriptional repressor of dusp1. 23826261_1 for evaluating the interaction between mir-29a and cav2 in both species, we screened the 3'-utr of porcine as well as human cav2 for potential mir-29a target sites. 23826261_2 this experiment proved the interaction between human as well as porcine cav2 target sites and mir-29a to be specific. 23826261_3 furthermore, it showed that mir-29a regulation of cav2 is conserved among both species. 26202983_2 these data suggest that rnf125 is a direct target of mir-15b, and its expression is regulated by mir-15b. 26202983_3 the repressive activity of mir-15b on its target, rnf125, becomes physiologically relevant if it is able to sustain the expression of rig-i that is negatively modulated by rnf125. 26159827_1 sox2 is a putative target for mir-146a. 26159827_2 these results were confirmed by western blotting for sox 2 as well as the known mir-146a target traf6. 26159827_3 sox2 is an effective target of mir-146a. 25449696_1 we also found that fas could reverse the apoptosis-inhibition effect induced by mir-181a. 25449696_2 moreover, hbv could inhibit cell apoptosis by down-regulating fas expression, which could be reversed by mir-181a inhibitor. 25449696_3 our data demonstrated that hbv suppressed apoptosis of hepatoma cells by up-regulating mir-181a expression and down-regulating fas expression, which may provide a new understanding of the mechanism in hbv-related hcc pathogenesis. 21338882_1 here we demonstrate that the repression of olig2 in p2 domain is controlled by mir-17-3p microrna-mediated silencing of olig2 mrna. 21338882_2 thus, both strands of mir-17 might contribute to olig2 silencing through binding to mir-17-3p and mir-302b targetsites within olig2 3'-utr . 21338882_3 we conclude that mir-17-3p binding sites alone are critical for mir-17 mediated silencing of olig2 3'-utr. 21338882_4 together, these results provide evidence that mir-17-3p alone is sufficient to silence olig2 expression. 23591709_1 furthermore, mir-210 suppressed cell apoptosis by inhibiting caspase activity and by regulating the balance between bcl-2 and bax levels. 23591709_3 western blot analysis demonstrated that bax, caspase-3 and caspase-9 protein levels decreased in cells that overexpressed mir-210 compared with controls. 26203762_1 as we have shown that scs are more radio-resistant than cb cells , the observed efficient dna repair after mir-542-5p inhibition in cb cells could either be due to the direct effects of pole1, fancl and maml1 overexpression, or the result of dedifferentiation of cb into scs . 26295043_1 figure 1: the potential target gene of mmu-mir-27a-5p, mcpip1, is upregulated in macrophage stimulated with lps. in summary, based on our previous study results, qrt-pcr was performed to validate the mrna levels of 18 inflammation-related candidate target genes, including mcpip1. 26295043_2 we, for the first time, identify mcpip1 as a target of mmu-mir-27a-5p by experimental validation and demonstrate that mmu-mir-27a-5p regulates the lps-induced upregulation of mcpip1. 22178568_1 these findings suggest that mir-124 may work as a basilic regulating factor to alleviate cell death in the process of ad by targeting bace1, play an essential role in the control of bace1 gene expression, and might be considered as a novel therapeutic targetin treating ad. 22178568_2 this finding suggested that down-regulation of mir-124 may promote the production of endogenous a through up-regulating the bace1 expression, and then further induce similar cytotoxic effects as the exogenous a insult. 22178568_3 we have predicted bace1 is one of mir-124 potential targetgenes. 21357421_1 end-point rt-pcr revealed the expression of l- and s-has2-as1 splice variants that differ only in their length of sequence complementarity with has2 and provided evidence of has2-as1 rna/has2 mrna duplex formation. 21357421_3 the calculations therefore support the existence of a dimer of has2 mrna and has2-as1 rna in the absence of sequestration of the rnas in kinetic or thermodynamic traps, which were not considered by this analysis. 21357421_5 8b depict the detection of a ribonuclease- and deoxyribonuclease-resistant has2-as1/has2 heteroduplex in ptc cytoplasmic rna. 26538296_1 further study revealed that mir-221 and mir-26b promoted msc migration by targeting pten, and downstream activation of akt and fak. 26538296_2 pten is downregulated by mir-221 and mir-26b. 26538296_3 taken together, our results indicate a role for mir-221 and mir-26b in the regulation of hgf-induced msc migration through the regulation of pten and its downstream signaling molecules akt and fak . 21750348_1 such a downregulation is occurred through direct interaction of the mir-190 with the 3'-utr region of the phlpp mrna, leading to a diminished phlpp protein expression and consequently, an enhanced akt activation and expression of vascular endothelial growth factor, an akt-regulated protein. 21750348_2 accordingly, it is very likely that as3+-induced akt activation is achieved through the downregulation of phlpp by mir-190, leading to a sustained akt activation and an increase in cell growth and proliferation, resulting in cell transformation. 21750348_3 in contrast, the mir-190in did not show inhibition on the phlpp 3'-utr reporter activity. 21750348_4 moreover, deletion of the mir-190-binding site within the phlpp 3'-utr abrogated the repressive ability of the mir-190 on the reporter gene activity , demonstrating specificity of the targetsequence for phlpp. 21750348_5 thus, these data provide strong evidence suggesting that as3+-induced mir-190 is crucial for the downregulation of the phlpp protein. 23710745_1 microrna-21 reduced tnf-alpha induced cardiomyocytes apoptosis . 23710745_2 tnf-alpha downregulated the expression of microrna-21 and upregulated the mrna and protein expressions of pten. 23710745_3 phosphorylation of pten, akt and foxo3a was enhanced in cardiomyocytes transfected with lenti-microrna-21 . 23710745_5 compared with cardiomyocytes treated with tnf-alpha , the phosphorylation of pten, akt and foxo3a as well as expression of ppten, paktser473, pfoxo3a and fasl were significantly suppressed in cardiomyocytes treated with lenti-microrna-21 and tnf-alpha . 23383207_1 we identified foxf2, reck and mtss1 as potential target genes of mir-182-5p using several algorithms which was confirmed by 3'-utr luciferase assay and western analysis. 23383207_3 this result suggests that the foxf2, reck and mtss1 mrnas are direct targets of mir-182-5p. 26759259_1 in addition, rna-immunoprecipitation and luciferase reporter assays showed that igf1 3'utr was a direct target of mir-29s. 26759259_2 our data also demonstrated that there existed a competition of mir-29s between igf1-3'utr and vegf mrna, and igf1-3'utr promoted angiogenesis at least in part via sponging mir-29s. 26759259_3 taken together, our study suggests that igf1-3'utr functions as a cerna in promoting angiogenesis by sponging mir-29s in osteosarcoma. 26759259_5 because igf-3'-utr shares regulatory mir-29s with vegf, we suspected that igf-3'-utr could modulate vegf. 26759259_6 taken together, all these results suggest an important role of igf1-3'-utr in modulating vegf by competitively binding mir-29s. 20852130_1 qrt-pcr revealed that mir-155* inhibited the expression of irakm mrna , whereas as-mir-155* enhanced it . 20852130_2 further study demonstrated that mir-155* inhibited irakm protein expression . 20852130_3 the results indicated that mir-155* suppressed renilla luciferase activity in a dose-dependent manner, and that the mutation in the seed sequence of the irakm 3'-utr, where mir-155* is predicted to bind bolished the suppression of renilla luciferase activity by mir-155* . 20852130_4 these results suggest that mir-155* and mir-155 function through irakm and tab2, respectively, in pdcs during tlr7 stimulation. 20173049_2 thus these results confirm the bioinformatics prediction that the 3'-utr of nfatc4 is targeted by mir-133a. 20173049_3 the results showed that the cells treated with the mir-133a mimic decreased nfatc4 mrna levels 65% compared with cells treated with the control mimic . 20173049_4 this result indicates that the expression level of nfatc4 can be negatively modulated by mir-133a, and that mir-133a may be a silencer of nfactc4. 20173049_5 collectively, these data demonstrat that nfatc4 is the target of mir-133a, and that silencing of nfatc4 by mir-133a may contribute to mir-133a-mediated anti-hypertrophy. 26836061_1 moreover, the microrna-124 expression level positively correlated with dlx3, negatively with osteoclastogenesis-related gene nfatc1. 26836061_2 our results indicate that dlx3 negatively regulates osteoclastic differentiation through microrna-124, which is partially responsible for the increased bone density in tdo patient. 26367773_1 therefore, we focused on evaluating foxp1, tp53inp1, tnfaip3, and tusc2 genes as mir-19a targets. 26367773_2 taken together, foxp1, tp53inp1, tnfaip3, and tusc2 were confirmed to be mir-19a target genes. 20797623_1 in accord with a previous study identifying the pten tumor suppressor gene as a direct target of mir-21, expression levels of mir-21 and pten mrna expression levels are inversely correlated during er-src transformation. 20797623_2 in addition, inhibition of mir-21 expression results in up-regulation of pten mrna expression. 25333257_1 altogether, our results showed fas signaling could promote chemoresistance in gi cancer through modulation of p-gp expression by -beta-catenin and mir-145. 25173609_1 mir-125b also inhibited the mrna and protein levels of scnn1a. 21693595_1 h2ax 3'utr is a direct target of mir-138. 21693595_2 furthermore, in u2os cells expressing flag-tagged h2ax cdna lacking its native 3'-utr, overexpression of mir-138 could not reduce the expression of exogenous flag-h2ax , while it downregulated endogenous h2ax expression . 21693595_3 taken together, these data suggest that h2ax 3'-utr is a direct target of mir-138. 21693595_4 figure 3. h2ax is a direct target of mir-138. 21693595_5 these findings suggest that mir-138 sensitizes cells to cisplatin and camptothecin mostly by downregulating h2ax. 26302266_1 all of the data indicated that rab11a was a direct target of mir-21. 26302266_2 mir-21 did not influence the mrna level of rab11a . 26302266_3 however, mir-21 mimics did inhibit the protein level of rab11a , indicating that rab11a expression may be regulated by mir-21 at the post-transcriptional level 23632416_1 the transcription factor v-ets erythroblastosis virus e26 oncogene homolog-1 was identified as a potential target of mir-222 using targetscan, and fivefold increased ets-1 protein expression in females was confirmed by western blot. 23632416_2 we demonstrated that mrna and protein levels of the enos transcription factor and putative mir-222 target, v-ets erythroblastosis virus e26 oncogene homolog 1 , were significantly increased in females compared with males, and we confirmed mir-222 targeting of ets-1 in vitro. 23632416_3 mir-222 regulates ets-1 and enos. 23632416_4 additionally, we found that mir-222 exerts its effects on enos in the cardiomyocyte through direct inhibition of the transcription factor ets-1. 26830228_1 to further confirm the direct targeting of hmga2 by mir-33b, we obtained a luciferase reporter 335 construct for the entire 3'-utr of hmga2 22113133_1 mir-34b has been showed to inhibit cell growth by targeting cyclin d1 and jag1, both of which are crucial genes covering various types of breast cancer. 22113133_2 our results show that the luciferase activity of the wild-type jag1 and cyclin d1 3'utr construct was significantly inhibited after the introduction of mir-34b into 293t cells, but not by the negative control. 22113133_3 these results demonstrate that jag1 and cyclin d1 are potential target of mir-34b. 22113133_4 furthermore, these data suggest that mir-34b may suppress tumor growth through the suppression of cyclin d1 and jag1 expression. 25407044_1 dsra is required for the downregulation of mreb cellular concentration during environmentally induced slow growth-rates, mainly growth at low temperature and during stationary phase. 25407044_2 dsra interacts in an hfq-dependent manner with the 5'region of mreb mrna, which contains signals for translation initiation and thereby affects mreb translation and stability. 18378902_1 hcmv ie1 protein synthesis is suppressed by by mir-ul-112-1. 21880893_1 osterix was a direct target of mir-637 in hmscs. 21880893_2 furthermore, as shown in figure 5, c and d, ectopic expression of mir-637 led to a decrease in osx in mrna and proteins. 21880893_3 moreover, suppression of endogenous mir-637 resulted in the up-regulation of osx in hmscs. 21880893_4 figure 5: osx was a direct target of mir-637. 21880893_5 our data confirmed that osx knockdown suppressed osteoblasts in hmscs, which was similar to the phenotypes induced by mir-637 restoration. 21880893_6 these results suggested that mir-637-induced differentiation was at least partly mediated by direct suppression of osx expression. 26151663_1 downstream target genes of mir-1181 were searched, and it was identified that mir-1181 degraded hoxa10 by targeting its 3' untranslated region in ovarian cancer cells. 26151663_2 figure 5. mir-1181 degrades hoxa10 by targeting its 3'utr in ovarian cancer cells. 20071580_1 however, bac36 mir consistently expressed elevated levels of viral lytic genes, including the immediate-early transcriptional activator rta . 20071580_2 at least one kshv microrna was capable of suppressing orf50 mrna, but poor seed sequence alignments suggest that these targets may be indirect. 20071580_3 we conclude that kshv mirna targets multiple pathways to maintain the latent state of the kshv genome, including repression of the viral immediate-early protein rta and a cellular factor, rbl2, that regulates global epigenetic reprogramming. 10972807_1 the gcvb deletion mutant has high constitutive synthesis of oppa and dppa, the periplasmic-binding protein components of the two major peptide transport systems normally repressed in cells growing in rich medium. 10972807_3 although the mechanism involving gcvb in the repression of these two genes is not known, oppa regulation appears to be at the translational level, whereas dppa regulation occurs at the mrna level. 19656885_1 here we demonstrate that mir-ul112 also targets the ul114 gene, and we present evidence that the reduction of ul114 by mir-ul112 reduces its activity as uracil dna glycosylase but only minimally affects virus growth. 20851997_1 taken together with previous reports that mir-17-92 inhibits apoptosis by suppressing pten via the mir-19 components, our results indicate that this mirna cluster promotes tumorigenesis by antagonizing both tumor-suppressing mechanisms, apoptosis, and senescence, through the activities of different mirna components encoded in this cluster. 25333573_1 furthermore, ldha was shown to be a direct target of mir-34a. 25333573_3 the current study demonstrated that ldha is a direct target of mir-34a in colon cancer cells. 25333573_4 these results demonstrate that ldha is a direct target of mir-34a in colon cancer cells. 18679415_1 transfection of melanoma cells with let-7a pre-mir molecules resulted in the downregulation of integrin beta mrna and protein expression. in addition, we cloned the 3'-utr of the integrin beta mrna containing the let-7a target sequence into a reporter plasmid and revealed that let-7a negatively regulates reporter gene expression. 18679415_2 the repressed expression of integrin beta accompanies with reduced invasive potential of melanoma cells transfected with synthetic let-7a molecules observed in boyden chamber assays. 18679415_3 on the other hand, the induction of integrin beta expression was achieved in melanocytes by transfection with let-7a anti-mirs, resulting in invasive behavior of transfected melanocytes. 18679415_4 in summary, we determined mirna let-7a to be an important regulator of integrin beta expression and showed that the loss of let-7a expression is involved in development and progression of malignant melanoma. 21813472_1 further study showed that mir-375 could interact with the 3'-untranslated region of igf1r and downregulate its expression. 21813472_2 the result showed that mir-375 could downregulate igf1r expression in both the mrna level and protein level . 21813472_3 interestingly, mrna expression of igf1r was negatively correlated with mir-375 in escc cell lines . 21813472_4 to validate whether igf1r is the direct downstream target of mir-375, a fragment of the 3'-utr of igf1r containing the potential mir-375 binding site was cloned into a vector with the firefly luciferase reporter gene. 22761336_1 mir-96 downregulates rev1 and rad51 to promote cellular sensitivity to cisplatin and parp inhibition. 22761336_2 mir-96 directly targeted the coding region of rad51 and the 3'-untranslated region of rev1. 22761336_3 these results suggest that endogenous levels of mir-96 downregulate rev1 and rad51 very mildly and that mir-96-mediated regulation is only one of the mechanisms that regulate rev1 and rad51 expression. 22761336_4 mir-96 is broadly conserved across many species as are the mir-96 binding sites in rad51 and rev1 transcripts , suggesting conservation of the trans-regulatory interactions between mir-96 and its target, rad51 and rev1. 26679164_1 using a luciferase-based reporter assay we found that mir-592 directly targeted the lhcgr. 26679164_2 these data demonstrated that mir-592 recognized and regulated lhcgr mrna through specific binding to its 3 ' utr. 26679164_3 using a lhcgr-3 ' utr luciferase-reporter assay, we confirmed that mir-592 recognizes and regulates lhcgr mrna through binding to its 3 ' utr. 21573166_1 the deletion of the mir-29a-binding site was able to abolish the role of mir-29a in suppression of luciferase activity of the pten 3'utr reporter. 21573166_2 furthermore, the overexpression of mir-29a was able to markedly downregulate the expression of endogenous pten at the levels of mrna and protein in hepg2 or mhcc-97l cells. 21573166_3 meanwhile, the mir-29a inhibitor was able to upregulate the expression of pten at the levels of mrna and protein . 21573166_4 the data showed that the expression level of mir-29a was inversely correlated with the expression level of pten , suggesting that mir-29a negatively regulates the expression of pten by directly targeting the 3'-utr of mrna. 21573166_5 as expected, we showed that the levels of pten were negatively correlated with the metastasis potential in a model of mhcc-97h cells/mhcc-97l cells , suggesting that pten is negatively associated with the expression of mir-29a. it supports that pten is a target gene of mir-29a. 21573166_6 therefore, our finding suggests mir-29a increases the migration of hepatoma cells through pten target gene. 18538733_5 re-expression of mir-203 reduces abl1 and bcr-abl1 fusion protein levels and inhibits tumor cell proliferation in an abl1-dependent manner. 22917588_1 further investigation revealed that fibroblast growth factor 9 and neurotrimin were two direct target of mir-182 in scs, with mir-182 binding to the 3'-untranslated region of fgf9 and ntm. 22917588_2 our data indicate that nerve injury inhibits sc proliferaton and migraton through rapid regulation of mir-182 by targeting fgf9 and ntm, providing novel insights into the roles of mirnas in nerve injury and repair. 22917588_3 post-transcriptional down-regulation of both fgf9 and ntm expressions by mir-182 through targeting their 3'-utr. 22105316_1 we also observed that cyclin g expression was up-regulated in hbv-infected patients, and cyclin g levels were inversely associated with mir-122 expression in liver tissues. 21806957_1 expression analysis revealed the osteoblast transcription factor sp7 as a target of mir-125b. 21806957_2 interestingly, long-term inhibition of mir-125b significantly up-regulated the sp7 mrna level by 1.9-fold compared with the negative control . 18987208_1 we also analyzed the downregulation of pmp22 after transfection of mir-9 in schwann cells. 18987208_2 the northern blot analysis shows the absence of mir-9 in schwann cells although the mir-9 precursor form is detected, in agreement with the specific expression of mir-9 in the brain . 18987208_3 the schwann cells were transfected with the mir-9 expression plasmid and showed weaker pmp22-like pattern of immunoreactivity, compared with the cells transfected with the mir-neg plasmid . 18987208_4 altogether, these results show that mir-9 downregulates pmp22 in vitro by binding to its 3'-utr. 26078353_1 furthermore, knockdown of tug1 also down-regulated heat shock transcription factor 2 , a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of mir-144. 26078353_2 microrna-144 inhibited the expression of hsf2 by binding 3'-utr of hsf2. 26078353_3 knockdown of tug1 also down-regulated heat shock transcription factor 2 , a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of mir-144. 26639035_1 up-regulated il-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of mir-365, suggesting that mir-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via il-6. 26639035_2 mir-365 regulates the expression of il-6 by binding with its 3'-utr the result indicates that mir-365 regulates the expression of il-6 by binding with its 3'-utr. 26192324_1 more importantly, the mirnas analyzed in this study not only included the mirnas like let-7a, mir-15b, mir24, mir-100 and mir-125 which may suppress the expression of cyclins a and b, and mirnas such as let-7a, mir24 and mir-125 which may regulate activity of cdk1, but also mirnas such as mir-181a, mir-221 and mir-222 which can target cdk inhibitors . 20618998_1 using bioinformatics analysis, we found that mir-221 and mir-222 contained specific binding sequences for the 3'utr region of the pten gene. 20618998_2 to confirm that pten is a target of mir-221 and mir-222, we cloned the pten 3'utr fragment containing the putative mir-221/222 target site into pgl3-control vector with a luciferase reporter gene . 20618998_4 furthermore, western blot analysis showed that pten was significantly upregulated in as-mir-221/222 transfected cells. in contrast, pten expression was downregulated in pmscv-mir-221/222 infected cells . 20618998_5 together, these data demonstrated that pten is a target gene of the mir-221/222 cluster. 20618998_6 these results define an important role for pten as a mediator of the biological effects of mir-221/222 in sgc7901 gastric cancer cells. 20618998_7 these data suggest that mir-221 and mir-222 impact the phenotype of sgc7901 cell by modulating the expression of pten and akt phosphorylation. 26376677_1 collectively, our findings suggest mir675 targets for hp1 isoforms including hp1alpha, hp1-beta, hp1gamma and inhibits their expression in liver cancer cells. 26376677_2 collectively, these observations strongly suggest that mir675 promotes h19 expression through upregulating and activating egr1 by targeting for hp1 isoforms. 18850008_1 to understand if the pdcd4 and pten downregulation was mediated by mir-21, we inhibited mir-21 expression, by using a chemically modified mir-21 inhibitor . 18850008_2 differing from pdcd4, pten expression was only partially inhibited by ras induction. 18850008_3 nevertheless, the partial downregulation of pten was abrogated by the antagomir-lna, thus showing that also pten is targeted by mir-21, in the ras-inducible thyroid system . 19380116_1 both kshv and ebv encode a mirna that downregulates micb, the two viral mirnas, mir-k12-7 and mir-bart2-5p, specifically downregulate micb expression to avoid attack by immune cells. 26189214_1 as predicted, the 3'-utr of the mrna encoding lhx2 harbors two mir-1238 binding sites , suggesting that lhx2 could be a potential target of mir-1238. 26189214_2 as illustrated in figure 3b, mir-1238 significantly attenuated the luciferase activities in a549 and ltep-alpha-2 cells transfected with the lhx2 3'-utr wildtype or mutant-1 but did not inhibit the luciferase activities in a549 and ltep-alpha-2 cells with the mutant-2 and mutant-1&2 constructs, suggesting that mir-1238 can selectively bind to the sequence of lhx2 3'-utr. 26189214_3 overexpression of mir-1238 3c significantly diminished lhx2 mrna and protein levels in a549 and ltep-alpha-2 cells,taken together, the results suggested that mir-1238 can directly target the 3'-utr of lhx2. 23845851_2 furthermore, we find that mir-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest mir-302b can activate caspase-3 and regulate the akt/pakt, bcl-2, bim expression to increase the cell apoptosis. 23845851_3 meanwhile, mir-302b also attenuates cyclin d1 and cdks expression to induce cell cycle arrest. 17892514_1 expression levels of mir-143 and -145 were significantly decreased in b-cell malignancies.transfection of raji cells with precursor or mature mir-143 or -145, respectively, causes growth inhibition. 25522282_1 mir-150 is an important suppressor of pancreatic ductal carcinoma and acts as a regulator of c-myb and muc4 in aggressive progress.the in vitro and in vivo assays of pancreatic cancer cells showed that mir-150 overexpression leads to reduced cell growth, clonogenicity, migration, invasion, modular cell cycles, and induced apoptosis. 25522282_2 moreover, mir-150 expression was inversely correlated with c-myb and muc4 activities in pancreatic tissue, cell lines, and nude mouse model. 26035691_1 cd44 is a direct and functional target of mir-34a as cd44 knockdown phenocopies mir-34a overexpression in inhibiting the metastasis of prostate cancer cells . 26035691_2 figure 4. cd44 is regulated by mir-34a in gastric cancer cells. 19955368_1 we then assessed the targeting of notch-1 and notch-2 by mir-326, given the seed matches noted in both 3'-utrs . 19955368_2 pre-mir-326 transfection caused substantial decreases in both notch-1 and notch-2 protein by immunoblot . 19955368_3 since mir-326 decreased protein levels of notch-1 and -2, we predicted that this mirna would be cytotoxic to gtscs. 23430263_2 screening was carried out using two different algorithms , and the results were confirmed using rna22 . in the present study, we found that both of mir-143 and mir-145 were decreased with odontoblast differentiation in vitro and in vivo. it is possible that klf4 and osx expression is relevant to expression of the mir-143 and mir-145 during odontoblast differentiation. 23430263_3 these data demonstrate that mir-145 binds to the 3'-utr of the klf4 and osx genes, resulting in inhibition of both the two gene expression. 23430263_4 this indicates that mir-143 and mir-145 regulate the cell differentiation via klf4 and osx pathways. 23430263_5 these results indicate that mir-145 and mir-143 arrest odontoblast differentiation by down-regulating klf4 and osx expression directly and that the down-regulation of mir-145 and mir-143 during odontoblast differentiation tunes down the repression of klf4 and osx, which in turn promotes the odontoblast differentiation. 23338610_1 all these findings together support the notion that mir-23b/27b directly targets nischarin and represses its expression. 23338610_2 overexpression of nischarin inhibited migration , supporting our hypothesis that the effects of mir-23b/27b are at least in part due to the suppression of nischarin. 26507500_1 as the results, ectopic expression of mir-141 resulted in a reduction expression of gh and ghrb to 12.8% and 17.6% at 24 hpf, 11.2% and 66.4% at 48 hpf , while mir-429a reduced the expression of gh, ghra, ghrb and igf2a to 62.3%, 37.1%, 59%, 72% at 24 hpf and 20%, 14%, 6.5%, 52.5% at 48 hpf compared to the control microrna mimic. 26507500_2 moreover, igf1, a major downstream mediator of the growth hormone pathway, was also significantly reduced by both mir-141 and mir-429a . 26507500_3 for the following experiments, mir-141 and mir-429a mimics or inhibitors were 1:1 mixed to give working solutions. 26507500_4 further, whole-mount in situ hybridization at 48 hpf demonstrated a dramatic reduction of gh mrna in pituitary following mir-141/429a injection . 26507500_6 these results demonstrate that gh, ghra, ghrb and igf2a are direct target genes of zebrafish mir-200s. 21147878_1 on checking using quantitative real time rt-pcr, the results showed that levels of the mirnas mir-155, mir-183, and mir-872 were significantly down-regulated . 21147878_2 results showed that cobalt-protoporphyrin-搃nduced ho-1 expression was significantly suppressed in cells overexpressed mir-155, mir-183, and mir-872 . 21189327_1 either mir-199a-5p or mir-199a-3p target brm mrna. 21189327_2 overall, therefore, the results of these experiments indicated that either mir-199a-5p or -3p negatively regulates brm production. 21189327_3 overall, these results support the contention that brm is a specific target of both mir-199a-5p and -3p in these cell lines. 23868977_1 fig. 6. e2f1 and hipk1 are direct targets of mir-17-92 mirnas. 23868977_2 the cells infected with pre-mir-19b and pre-mir-92a showed reduced hipk1 levels compared with nc-infected cells, which suggests that the mir-17-92 mirnas regulate e2f1 and hipk1 expression in vivo at the post-transcriptional level. 26055874_1 mafb, a transcription factor of maf family members, was identified as a target gene of mir-223. 26055874_2 combined bioinformatics results with the dual luciferase reporter assay , we identified mafb as one of mir-223 target genes for further investigation. 26055874_3 these findings demonstrated that mir-223 regulates the npc development by targeting mafb expression, and implicates mir-223 as a candidate target for npc diagnosis and treatment. 22991189_2 however, overexpression of tbk1 partially rescued mir-200c mediated apoptosis induced by ionizing radiation. 25405338_1 to explore the mechanism of mir-34a in the hepatoprotective effects of h2s, the expression of nrf-2, nqo1, gst and ho-1 was measured in the young and old rats after injection of mir-34a mimic or inhibitor. 25405338_2 as shown in figure 6a and 6b, mir-34a mimic could reduce the expressions of nrf-2, nqo1, gst and ho-1 in the young rats after hepatic i/r pretreated with nahs, suggesting that the promotion of nrf-2-mediated signaling pathway by nahs might act through down-regulation of the mir-34a level. 25405338_3 mir-34a inhibitor significantly increased the expressions of nrf-2, nqo1, gst and ho-1 in the old rats after hepatic i/r injury with nahs treatment , suggesting that mir-34a-mediated nrf-2 signaling pathway is involved in hepatoprotective effects of h2s. 26725319_1 luciferase reporter assays, however, showed that bovine pck1 expression is repressed by bta-mir-26a in hepg2 hepatocyte cells. 21501518_1 we demonstrate that restoration of mir-200c causes a 36% reduction in luciferase activity when the 3' utr of lepr is placed downstream of luciferase . 25253996_1 we identified pten as a functional target for mir-492. 25253996_2 we also investigated the mechanism which underlies the regulation of tumor cells by mir-492 and showed that mir-492 activated the pi3k/akt pathway through targeting phosphatase and tensin homolog . 25253996_4 pten is a functional target of mir-492 25399950_1 these findings indicated that mir-148a bound and negatively regulated the transcription of scrn1 and that this regulation was more negatively influenced by the variant a allele in vitro. 25399950_4 a significant reverse correlation between mir-148a and scrn1 mrna expression was identified in 32 gc tissues. 25399950_5 our results from the luciferase assay indicated that mir-148a mediated scrn1 translational regulation. 26032086_1 acvr1, msk1, tgif2, and rock1 are reported target genes of mir-148a , and we confirmed that mir-148a mimics can repress their expression in hk-1 cells. 25450356_1 ccnd1 is identified as a direct target of mir-383 in glioma cells. 25450356_2 targetscan showed that the 3' -utr of ccnd1 has a predicted binding site of mir-383. 25450356_3 to investigate whether ccnd1 was directly targeted by mir-383, a luciferase activity assay was performed to validate interaction between mir-383 and the predicted binding site. 21893020_1 overexpression of mir-193b in melanoma cells represses mcl-1 expression. 21893020_2 this result suggests that mir-193b has multiple binding sites in the mcl-1 3'-utr, one of which seems to be a seedless target figure 3 mir-193b directly target the 3'-utr of mcl-1. in summary, this study demonstrates that mir-193b is down-regulated in primary melanoma and suggests that mcl-1 is directly regulated by mir-193b in melanoma cells. 21893020_3 reduced mir-193b expression could contribute directly to elevated expression of mcl-1 in melanoma cells. 26296645_1 transfection of let-7b mimics significantly decreased the expression of caspase-3 and the luciferase activity of cells transfected with luciferase vector containing the 3- utr of human caspase-3 indicating that let-7b directly targeted caspase-3. 23285158_1 we also analysed the interaction of mir-133b with the pitx3 and pitx3 target genes drd2a and drd2b, tyrosine hydroxylase and dopamine transporter by microinjection of the pitx3-3'utr sequence. 23285158_2 pitx3 activates the expression of different genes such as th, dat and drd2 in dopaminergic neurons and it also induces mir-133b transcription by rna polymerase ii and mirna binding to 3'utr-pitx3 , inducing mrna degradation and blocking the translation of pitx3. 23285158_3 considering the importance of mir-133b and pitx3 in the differentiation of dopaminergic neurons, we studied the cocaine-induced changes in the expression of mir-133b and pitx3 at 24 and 48 hpf by qpcr. 24987958_1 overall, our data suggest that raw264.7 cells subjected to h/r exhibited decreased mir-146a expression, elevated levels of traf6 and irak1, and the release of proinflammatory cytokines. 24987958_2 in contrast, a decrease in mir-146a by the mir-146a inhibitor elevated traf6 and irak1 expression . 24987958_3 these results imply that mir-146 is able to directly bind to traf6 or irak1 regulatory sequences in their 3'-utrs, decreasing their expression in h/r-induced macrophages. 18155131_1 dnd1 alleviates mir-430 repression of nanos1 and tdrd7 in primordial germ cells of zebrafish next, we examined whether the reduction in nanos1 and tdrd7 following loss of dnd1 depends on the ability of mir-430 to interact with these genes. 26549227_1 collectively, we conclude that mir-506 can attenuate the expression of sphk1 through directly targeting 3'utr of sphk1 mrna in hepatoma cells. 26549227_2 mir-506 is able to down-regulate sphk1 in hepatoma cells 20435889_1 these results suggested that mir-221 target tnfalpha mrna for rapid decay in tolerant cells but does not regulate translation per se. 20435889_2 together, these results support that the mir-221 binding site in the tnfalpha 3'-utr mediates mrna decay, whereas mir-579 and mir-125b binding sites mediate translation arrest. 21461636_1 luciferase assay showed that mir221and mir222 specifically bindto the p27kip1 and p57kip2 mrna 3'-untranslated regions, implicating p27kip1 and p57kip2 as mir221/mir222 target. 21461636_2 these data indicate that, as the result of mir221 and mir222 downregulation, posttranscriptional regulation of p27kip1 and p57kip2 controls high-glucose- and age-induced inhibition of both ec and epc cell-cycle progression. 23300478_1 gcvb is a direct regulator of phopq. 24166509_2 collectively, our findings show the critical roles of mir-106b-5p and its targets, rbl1, rbl2 and casp8, in glioma tumorigenesis and provide potential candidates for malignant glioma therapy.oncogene 23160513_2 these observations confirm that mir-494 binds atf3 3' utr and inhibits atf3 transcription in vitro. 23160513_3 these observations indicate that the ischemic-responsive gene mir-494 is expressed earlier than the atf3 gene and that mir-494 may function as a transcriptional regulator to atf3 after renal i/r injury. in addition, as mir-494 increased, translocation levels of atf3, which reflected transcriptional activity, were decreased in the kidneys after i/r . 23160513_4 together, our data suggest that mir-494 and atf3 play important pathophysiological roles in the kidneys after i/r. 26404754_1 these results demonstrated that zbtb7a was a direct target of mir-100 . 26404754_2 as expect, when mir-100 was knocked down, the upregulated luciferase activity of the zbtb7a pmirglo-3'-utr vector was observed 25200485_1 pcgem1 and mir-145 exhibited reciprocal regulation;downregulation of pcgem1 expression in lncap cells increased expression of mir-145, while overexpression of mir-145 decreased pcgem1 expression.transfection of the mir-145 expression vector and sirna pcgem1 inhibited tumor cell proliferation, migration, and invasion, and induced early apoptosis both in vitro. 26125274_1 to determine whether cx43 is a direct target of hsa-mir-206, luciferase reporters containing the cx43 3'-utr or a cx43 mut 3'-utr were constructed and co-transfected with mirna mimics or the negative control into mda-mb-231/436 cells,indicating that cx43 is a direct target of hsa-mir-206. 19850741_1 a marked reduction in the luciferase/renilla ratio was seen for mcl-1, cxxc6, and cdk6 constructs transfected with synthetic mir-29b but not with the control. 19850741_2 as shown in figure 4g, cxxc6, cdk6, and mcl-1 mrna levels were lower in mir-29b-transfected samples with respect to the controls at 24 hours . 19850741_3 furthermore, the observed luciferase/renilla reduction was abrogated when we cotransfected a mutated luciferase reporter vector containing the 3'-utr of mcl-1, cxxc6, and cdk6 with 4 deleted nucleotides at the site of interactions with mir-29 . 19501585_2 this result indicated that mir-373 targetsite 2 of lats2-3'-utr plays a more important role than mir-373 targetsite 1 in mir-373 mediating lats2 protein expression. 19501585_3 these data suggest that mir-373 specifically down-regulates lats2 at the posttranscriptional level. 25613580_2 luciferase reporter assays showed that mir-26a significantly decreased the luciferase activity of the epha2 wt 3- utr but not that of the mutant, indicating that epha2 is a direct target of mir-26a. 22307873_1 these findings suggest that an inherited polymorphism of a let-7 mirna binding site in kras leads to abnormal endometrial growth and endometriosis. in summary, the kras variant that prevents let- 7 mirna inhibition of kras was significantly increased in women with endometriosis. 19464056_2 on the contrary, an extracellular signal-regulated protein kinase 5 , which was determined to be a target of mir-143 in colon cancer dld-1 cells, was time-dependently down-regulated at the translational level after the treatment. 26879016_1 cx43 mrna and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in mda-mb-231 cells after reducing mir-206 expression but decreased in mcf-7 cells after elevating mir-206 expression, which demonstrated a significantly negative correlation between mir-206 and cx43 expression . 26879016_2 mir-206 can regulate cx43 by binding to specific sites of cx43 3'-utr . 23541921_2 considering the facts that core tfs also directly regulate linc-ror transcription, we therefore suggested that linc-ror and core tfs formed a regulatory feedback loop in hescs. 23541921_3 these results indicate that linc-ror does not regulate oct4 at the transcriptional level but may regulate them at the posttranscriptional level. 23541921_4 these data suggest that linc-ror shares regulatory mirnas with the core tfs oct4, sox2, and nanog and that mir-145 may be one of the critical regulatory mirnas for these genes. 23541921_5 taken together, these data suggest that linc-ror functions as an mirna sponge to reduce the efficient concentration of mir-145. 23541921_6 these results indicate that linc-ror functions as an endogenous mir-145 sponge to avoid mir-145 increases in self-renewing hescs. 23541921_7 these results indicated that linc-ror deficiency results in obvious changes in the expression of mir-145 and core tfs in self-renewing hescs only after long-term culture. 23541921_8 these data are consistent with the hypothesis that linc-ror does not directly regulate mir-145 and core tf transcription but instead regulates them through posttranscriptional finetuning. 23384942_1 mir-7 is downregulated in metastatic cscs, mir-7 suppresses the expression of klf4 gene, klf4 promotes self-renewal of cscs. 23384942_2 these clinical data are consistent with our notion that mir-7 suppresses brain metastasis through inhibition of klf4 expression. 23384942_4 3a and strongly support the notion that mir-7-2 specifically suppresses brain metastasis by down-regulating klf4. 21841775_1 on the basis of these observations, we determined the functional relationship between mir-128b and the 3- utr of these putative mir-128b target genes by luciferase assay. 21841775_2 overexpression of mir-128b led to decreased activity of the firefly luciferase gene fused to the 3- utr of creb1, sp1, reln, ppp1cc and rcs , with no effect on ppp1ca. 21841775_4 of the six mir-128b targets, only rcs showed a specific extinction learning-induced decrease in mrna expression, which was reflected by a time-dependent, transient decrease in rcs protein expression . 21841775_5 these observations, together with our data demonstrating a specific effect of extinction training on rcs mrna and protein expression in the ilpfc , as opposed to the general effect of learning on ppp1cc, prompted us to focus on the interaction between mir-128b and rcs, and its contribution to the formation of fear extinction memory. 26397753_1 rnase l is a target of mir- 146b. 26397753_2 rnase l is a target of mir-146b by directly binding to its 3'-utr. 26434590_1 ap2alpha transcription factor is directly regulated by mir-221&222. 26434590_2 to verify the hypothesis of ap2alpha as a direct target of mir-221&222, we analyzed its expression level in nhem and some differently staged melanoma cell lines. 26434590_3 all together these experiments demonstrated that mir-221&222 directly interact with and repress ap2alpha. 26434590_4 accordingly, mir-221 or mir-222 enforced expression in me1007 and me1402/r primary melanoma cells strongly suppressed ap2alpha. 25649327_1 ectopic expression of mir-362-3p increased proliferation and anchorage-independent soft agar growth and its expression inhibition had opposing effects that were associated with regulation of its direct target-tob2 in hcc cells. 25649327_2 inhibition of tob2 recapitulated the effects of mir-362-3p overexpression, whereas enforced tob2 expression reversed the promoting effects of mir-362-3p. 25649327_4 these data indicate that hsa-mir-362-3p can target tob2 mrna and inhibit its protein expression. 26731986_1 the luciferase reporter assay revealed that hur was a target for mir-31. 26731986_2 furthermore, western blot analysis also showed the strong inhibitory effect of mir-31 on hur expression . in contrast, inhibition of mir- 31 increased the protein level of hur . 19141645_1 mir-210 and mir-373 regulate the dna repair genes rad52 and rad23b. 19141645_2 we find that mir-210 target rad52, a member of the hdr pathway, whereas mir-373 can targetboth rad52 and rad23b. 19141645_3 we did not detect changes in the accumulation of either rad52 or rad23b mrna levels. 19141645_4 taken together, these findings further suggest that mir-210 and mir-373 forced expression each can cause the down-regulation of rad52 and rad23b expression, respectively, via a mechanism that target the 3'-utr of these genes. 23754151_2 furthermore, the overexpression of mir-708 reduced the expression of akt1, ccnd1, mmp2, ezh2, parp-1 and bcl2 in a172 and t98g cells. 19524505_1 mir-26a directly represses expression of cyclin d2 and cyclin e2. 19524505_3 although infection with mscv-mir-26a did not affect the abundance of cyclin e1 and cdk6 , significantly reduced levels of cyclin d2 and cyclin e2 were observed in cells with enforced mir-26a expression . 19524505_4 when introduced into hepg2 cells, constructs with intact mir-26a binding sites were expressed at significantly lower levels than the mutant constructs, consistent with direct functional interaction of endogenously expressed mir-26a with these sites . 19524505_5 these data document that mir-26a directly represses expression of cyclin d2 and cyclin e2, providing one mechanism through which this mirna arrests cell-cycle progression. 26830849_1 these results identify phlpp2 as a bona fide direct target of mir-181b. 26830849_2 collectively, these results identify phlpp2 as a direct target of mir-181b that may mediate mir-181b's effects on the insulin signaling pathway. 26820911_2 co-transfection of the mir-194 mimic and the luciferase construct reduced luciferase activity, indicating that mir-194 directly targets on the bmp1 3'-utr. 26820911_3 we performed qpcr to evaluate bmp1 mrna levels after mir-194 mimic/inhibitor or peitc treatment. 26820911_4 we found that both mir-194 mimic and peitc treatments decreased bmp1 expression. 26506517_1 these results demonstrated the mechanistic role of mir-92a on rbm4 reduction in crc tissues and cells. 21343296_1 in addition, we found that mir-520b could indirectly regulate il-8 transcription by targeting hbxip. 21343296_2 we found that the mir-520b mimics were able to markedly decrease the expression of endogenous hbxip in lm-mcf-7 and mda-mb-231 cells, whereas hbxip expression was significantly up-regulated in mcf-7 cells with anti-mir-520b . 21343296_3 taken together, these data suggest that mir-520b is able to regulate breast cancer cell migration by directly targeting hbxip. 21343296_4 overall, these data strongly suggest that the il-8 gene is a direct target of mir-520b and is involved in breast cancer cell migration. 21343296_6 these data suggest that mir-520b regulates il-8 indirectly. 19888323_1 recently it was reported that the expression of the nearby genes cdkn2a andcdkn2b as well as the non-coding anril was linked with the risk genotype , . the positive correlation between cdkn2a, cdkn2b and anril that has previously been reported , was also found in the data sets under investigation here. 22356413_1 rpra interferes with translation and reduces csgd mrna levels by direct interaction. 20498642_1 similar to let-7, mir-30 is reduced in bt-ics, and the protein level of ubc9 and itgb3 , the target genes of mir-30, is markedly upregulated. 20498642_2 similar to let-7, the expression of mir-30 is reduced in bt-ics, and its target genes, ubc9 , an e2-conjugating enzyme essential for sumoylation, and integrin b3 , are upregulated at protein level. 20498642_3 therefore, mir-30 regulates itgb3 and ubc9 expression by directly targeting their 3' utr and inducing translational repression. in addition to ubc9, we found that itgb3 is also a direct target of mir-30, as mir-30 suppresses the luciferase activity of a reporter carrying the sequence of the itgb3 3' utr, whereas mutation at this target sequence abolishes the suppression effect. 23301034_1 the mature transcripts of the 4 members of the mir-181 family were all found to be significantly increased in differentiated hescs, and mir-181c had the highest expression level . 23301034_2 we also found that the expression levels of the mir-181c/d primary transcripts were notably elevated after differentiation in comparison to the primary transcripts of mir-181a and mir-181b . 23301034_3 taken together, these results show that mir-181 directly regulates carm1 by targeting its 3'-utr and that mir-181c may play a prominent role among the 4 members during hesc differentiation. 22379033_2 the mir-15/16 family is highly expressed in nk cells, decreases upon cytokine activation, and directly represses the murine ifn-gamma 3'-utr. 18304967_1 the most commonly cloned mature sequences derived from the previously annotated mir-128a and mir-128b were shown by landgraf et al to be identical . 18304967_2 the sequences are therefore renamed mir-128-1 and mir-128-2.loh of microrna-128b, which resides on the 3p22 locus, would be equivalent to losing a tumor suppressor gene because microrna-128b downregulates the expression of egfr. 18304967_3 microrna-binding predictions were confirmed by manually analyzing the egfr 3'-utr for binding sites of microrna-128b. 26882816_1 luciferase reporter assay revealed that cyclin e was the target of mir-503. 26882816_2 figure 4. mir-503 suppresses cyclin e protein levels. 26882816_3 target scan was used to predict mirna target genes and cyclin e was suggested to be a direct target gene of mir-503. 26882816_4 we found that the cyclin e protein level was markedly decreased in rmcs transfected with mir-503 mimics. 26882816_5 the results of the dual-luciferase assay indicated that cyclin e is a direct target gene of mir-503. 26882816_7 other studies have confirmed that mir-503 may directly suppress cyclin e and control the expression of cell cycle proteins. 19920351_3 relative to the control, overexpression of mir-2861 downregulated endogenous hdac5 protein . 19920351_4 this showed that mir-2861 regulates runx2 protein levels by targeting hdac5 in osteoblast differentiation. 19920351_6 northern blotting showed that bmp2 induced the expression of mir-2861 in bmscs . 19920351_7 alp activity and osteocalcin secretion were increased by transfection of pre-mir-2861 . 19920351_8 the level of runx2 protein was enhanced, whereas hdac5 protein level was reduced after transfection of pre-mir-2861. 20603000_3 collectively, these data indicate that mir-103/107 target the dicer 3' utr. 26446789_1 we identified gas5 as a target of microrna-222 and showed that mir-222 could inhibit the expression of gas5. 26446789_2 interestingly, gas5 could also repress mir-222 expression. 26446789_3 a pulldown assay further validated that gas5 could directly bind to mir-222. to summarize, mir-222 decreases the expression of gas5 through the mir-222 binding site. 26446789_4 taken together, our data indicated that mir-222 is able to directly bind to gas5. 26446789_5 these findings indicated that p27 is a target of mir-222, confirming the previous reports . 26446789_6 these data indicated the existence of specific crosstalk between gas5 and p27 through competition for mir-222 binding. in summary, these data indicated that gas5, by binding to mir-222, influences the level of p27 protein. 26446789_7 thus, we concluded that gas5 inhibits the activation and proliferation of primary hscs through regulation of mir-222 and p27. 18756266_1 mir-125b, mir-324-5p and mir-326 targetand functionally suppress smo. 18756266_2 consistent with these findings, we observed a significant reduction in mrna levels of endogenous hh targetgenes in response to mir-125b, mir-326 and mir-324-5p overexpression in mb cells . 18756266_3 notably, a synergistic effect between mirnas was observed, as indicated by the strong reduction of gli1 mrna levels when mir-324-5p and mir-326 were co-overexpressed . 22871495_1 using bioinformatics and biological approaches, we found that jagged-1 and hes-1, two key components of notchpathway, were direct target of mir-524-5p. 22871495_2 thus, we have identified that mir-524-5p behaves as a tumor suppressor by negatively targeting jagged-1 and hes-1 and provides an additional option to inhibit this oncogene in gliomas. in sum, these data indicated that mir-524-5p directly regulated by jagged-1 and hes-1 in glioma. 22871495_3 these data indicated that mir-524-5p directly modulated jagged-1 and hes-1 expression by binding to the respective 3'-utr. 22871495_4 taken together, our data suggested that hes-1 and jagged-1 were important target of mir-524-5p in glioma. 23604034_1 the mir-150-揹ependent suppression of luciferase activity was completely abrogated by mutations of the putative mre , confirming that cbl and egr2 are new mir-150 direct targets. 23604034_2 inaddition totheknown mir-150 target myb, we also identified cbl and egr2 as bona fide targets and shrna-mediated suppression of these genes recapitulated the pro-apoptotic effects observed in leukemic cells with mir-150 ectopic expression. 23604034_3 after screening more than 30 predicted mir-150 predicted targets using qrt-pcr and luciferase reporter assays, we confirmed that myb is a mir-150 direct target and also identified 2 new mir-150 direct targets that are often highly expressed in mll-associated leukemias; namely cbl and egr2 . 20008935_1 to determine whether pten down-regulation by mir-19 had any functional impact, we examined their functional interaction using an in vivo apoptosis assay in xenopus embryos. 20008935_2 consistent with pten being a key target of mir-19, injection of mir-19 and pten individually gave rise to opposite phenotypes, with mir-19 promoting cell survival and pten inducing apoptosis . 20008935_3 altogether, our findings indicate that the repression of pten by mir-19 occurs not only at the expression level, but also at the functional level, both of which are dependent on the intact mir-19-binding sites within the pten mrna. 21351256_1 mir-34c was found to negatively regulate the oncogenes e2f3 and bcl-2, which stimulates proliferation and suppress apoptosis in pca cells, 12679032_3 we identify the pro-apoptotic gene hid as a target for regulation by bantam mirna, providing an explanation for bantam's anti-apoptotic activity. 24967963_1 in this study, we found that hypoxia induces mir-424 expression and that mir-424 in turn suppresses the level of pdcd4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3' untranslated region. 25187057_1 mir181c promotes apoptosis and suppresses proliferation of metanephric mesenchyme cells by targeting six2 in vitro. 25187057_3 these results revealed the ability of a single mirna-mir181c to downregulate the expression of six2, restrain the proliferation and promote the apoptosis that even makes the nephron progenitor phenotype lose mm cells, suggesting a potential role of mir181c during the kidney development. 26841045_2 ,indicating mir- 21 enhanced hif- 1alpha activity by targeting the 3'- utr of chip in ucbmscs. 26841045_3 western blot results after over-expression of mir- 21 mimics or treated with the mir- 21 inhibitors were consistent with the results from the luciferase experiments,providing further confirmation that the 3'- utr of chip is the direct target of mir- 21. 21935352_1 mir-125b binds the 3' utr of human and zebrafish p53 mrnas. 21935352_2 ectopic expression of mir-125b by transfection of mir-125b duplex into hek-293t cells suppresses by ;60% the activity of a renilla luciferase construct containing the mir-125b mres of human or zebrafish p53 at its 3' end. 21935352_3 finally, we checked mir-125b regulation of protein expression in a subset of p53 network target for which reliable western blotting was possible. 21935352_4 mir-125b significantly downregulated the protein levels of human bak1, ppp1ca, tp53inp1, ppp2ca, cdc25c, and tp53 in sh-sy5y neuroblastoma cells . in mouse n2a neuroblastoma cells, mir-125b significantly downregulated mouse bak1, ppp1ca, puma, and itch protein . 21935352_5 we identified 20 direct target of mir-125b in the p53 network, including 15 novel target like zac1, puma, itch and cdc25c, and also target like bak1 and tp53 that were identified in previous studies .// 21935352_6 by using a gain- and loss-of-function screen for mir-125b target in humans, mice, and zebrafishand by validating these target with the luciferase assay and a novel mirna pull-down assay, we demonstrate that mir-125b directly represses 20 novel target in the p53 network. 18593903_1 the cgi spanning exon 1 and intron 1 of mir-1-1 was methylated in hcc cell lines and in primary human hccs but not in matching liver tissues. 18593903_2 the mir-1-1 gene was hypomethylated and activated in dnmt1-/- hct 116 cells but not in dnmt3b null cells, indicating a key role for dnmt1 in its methylation. 18593903_5 the expression of foxp1 and met harboring three and two mir-1 cognate sites, respectively, in their respective 3'-untranslated regions, was markedly reduced by ectopic mir-1. 18593903_6 up-regulation of several mir-1 targets including foxp1, met, and hdac4 in primary human hccs and down-regulation of their expression in 5-azac-treated hcc cells suggest their role in hepatocarcinogenesis. the inhibition of cell cycle progression and induction of apoptosis after re-expression of mir-1 are some of the mechanisms by which dna hypomethylating agents suppress hepatocarcinoma cell growth. 26678889_1 bioinformatic analyses using pictar and targetscan software indicated that mir-9, mir-96, mir-130a,mir-182, mir-301a/b, mir-454, mir-507, mir-721, mir-1271, mir-4295, and mir-3666 may target hes1. 26678889_2 a negative correlation between the expression levels of mir-9 and hes1 was observed. 26678889_3 the conserved sequences of mir-9 binding sites in the 3'- utr of hes1 were shown in fig. 26678889_4 3a.to evaluate the direct interaction between the 3'-utr of hes1 and mir-9, the hes1-psicheck2 construct was cotransfected into 293t cells with mir-9 mimics or a mir-9 scrambled negative control. 26455548_1 protein expression of mir-126 target genes, bcl-2, p53, and kras, were analysed in sw480 mir-126, sw480control and sw480 mir-scrambled cells . 26455548_2 sw480 cells showed increased levels of p53 protein and reduced protein expression for bcl-2. 26408293_1 the introduction of mir-216b suppressed gc cell proliferation and cell cycle progression by targeting hdac8, an oncogene shown to promote malignant tumor development with a potential mir-216b binding site in its 3' untranslated region. 26408293_3 these results further suggested that mir-216b might suppress hdac8 expression by targeting the 3'-utr of hdac8 mrna. 26408293_4 our findings suggest that mir-216b inhibits gc cell proliferation and cell cycle progression by inhibiting hdac8 expression. 22465663_3 erk1 knockdown can block cell proliferation induced by mir-483-5p inhibition. 22465663_6 taken together, these results demonstrate that erk1 is directly regulated by mir-483- 5p at the post-transcriptional level. 26622375_1 western blot analysis was performed to examine the expression of emt-related markers. in the sw620-si20a cells, knockdown of mir-20a upregulated the timp-2 and downregulated the mmp-2 and mmp-9 protein levels. 26622375_2 overexpression of mir-20a inhibited the expression of timp-2 and induced the expression of mmp-2 and mmp-9 . 26622375_3 these data indicate that mir-20a enhances emt by regulating the expression of timp-2, mmp-2 and mmp-9. 21276447_1 cd36, lox-1, and sra expression were regulated after incubation with mir-29a mimic and inhibitors. 21276447_4 the levels of lox-1, cd36 and sra were detected by western blot. 21276447_5 these results indicate that mir-29a regulates sra and cd36 expression at the transcriptional and translational levels and affects lox1 expression at the posttranscriptional level. 22452878_2 pita and miranda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3' untranslated region of viral gene m1 crna, but not to pb2 and pa. as detected by a luciferase reporter system, let-7c directly targeted the 3'-utr of m1 crna, but not pb2 and pa. 26254095_1 taken together, these results suggest that mir-302b suppresses hcc cell invasion by targeting akt2. 26254095_2 these results further suggest that mir-302b suppresses tumor invasion by directly targeting akt2. 26472185_1 these data indicated that mir-320a downregulates vdac1 expression through directly binding to the 3- utr of vdac1 in hela cells 22910415_1 also, expression levels of dicer and ccnd1 , which are known targetgenes of the let-7 family were upregulated. 22910415_2 we examined expression levels of dicer and ccnd1 , which are known targetgenes of the let-7 family. 22910415_3 to address whether let-7g affects its targetgenes in the ewing sarcoma cell line, we examined expression levels of dicer and ccnd1 , which are known targetgenes of the let-7 family. 17243163_5 second, given that ulms are benign and rarely progress to malignancy, a high level of let-7 mirnas in ulms may be the/r/nprotective factors preventing overexpression of their targeting oncogenes, such as ras and myc. 20533548_2 these results suggested that pdcd4 might be the potential targetgene of mir-21 in tgf--beta1-stimulated myofibroblast differentiation. 20533548_3 to further investigate whether mir-21 directly bound to 3'-utr of pdcd4 and inhibited pdcd4 expression in fibroblasts, the fragment of 3'-utr of pdcd4 mrna with the putative mir-21 binding sequence was cloned into a pgl3 vector at the downstream of the luciferase gene and cotransfected the pgl3 construct with either mir-21 mimic or mir-21 inhibitor into mrc-5 fibroblasts using lipofectamine 2000. 20533548_4 these results implied that mir-21 could bindto 3'-utr of pdcd4 and inhibit its expression in fibroblasts. 21118128_1 both decreased expression of mir-15a and mir-16-1 and increased nucleolin have been shown to be associated with increased bcl2 expression and resistance to apoptosis in the common human disease, chronic lymphocytic leukaemia. 21289483_1 our results demonstrated mir-145 in the negative regulation of egfr and nudt1 expressions at both mrna and protein levels. 21289483_2 this predictive participation of hsa-mir-145 in the regulation of egfr and nudt1 prompted us to further investigate their roles in the tumorigenesis process. 21289483_3 effects of mir-145 transfection on the expressions of epidermal growth factor receptor and nucleoside diphosphate linked moiety x-type motif 1 in human lung adenocarcinoma cells transfected with pep-mir-null or pep-mir-145. 21289483_4 overexpression of mir-145 led to significant downregulation of egfr and nudt1 mrna expressions. 21289483_5 as demonstrated by western blotting, the enforced expression of mir-145 in the three cell lines led to a decrease of egfr protein and a corresponding sharp decrease of nudt1 protein . 21289483_7 our report demonstrates that egfr and nudt1 are potential target of mir-145 in lung adenocarcinoma. 21289483_8 by suppressing egfr and nudt1, mir-145 inhibits cell proliferation. 26883911_3 bcpap cells express high levels of mir-146-5p, which reduces smad4 basal expression . 26883911_5 smad4, a crucial protein in the canonical tgf--beta signaling pathway, was validated as a target of mir-146b-5p in bcpap, tpc-1 and pccl3 cells . 26883911_6 the authors showed that mir-146b-5p targets the 3'utr of smad4. 26164457_1 mir-27a targets sfrp1 in glioma. 26164457_2 mir-27a binds to 3'-utr of sfrp1 and activates wnt/ beta-catenin signaling. 23682839_1 we investigated in detail one mirna, mir-24, and found that it is a novel regulator of oxt and controls both transcript and peptide levels of oxt. 23682839_2 furthermore, we found that an mirna, mir-24, that in silico analysis suggested would interact with the oxt mrna, does indeed reduce transcript and peptide levels of oxt in vitro. 23682839_3 these findings show that mir-24 can interact with the oxt mrna and inhibit translation from the chimeric transcript. 23682839_4 our data showed that mir-24 could target the boundary region between the coding sequence and 3- utr and inhibit oxt production. 20346171_1 as knockdown of mir-21 increased timp3 protein expression and luciferase reporter activity, our data suggests that mir-21 could promote invasion in breast cancer cells via its regulation of timp3. 20346171_2 the timp3 3'-utr is a targetfor mir-21. 20346171_3 our study suggests that the effect of mirna-21 expression on cell invasion may be due to the regulation of timp3 expression. 20346171_4 these data demonstrate that mir-21 regulates timp3 expression at the transcriptional level. 26201448_1 mir-221 showed an inverse correlation with vegfr2 expression . 26201448_2 also, vegfr2 was positively associated with better survival whereas mir-221 negatively correlated with survival . 22328513_1 we report that mir-195, mir-24-2 and mir-365-2 act as negative regulators of bcl2 through direct binding to their respective binding sites in the 3'-utr of the human bcl2 gene. 22328513_2 taken together, these results demonstrate that mir-195, mir-24-2 and mir-365-2 could negatively regulate bcl2 at both the transcriptional as well as post-transcriptional levels. 22328513_4 taken together, these results confirmed that mir-195, mir-24-2 and mir-365-2 directly regulate expression of the anti-apoptotic protein bcl2 and induce apoptosis. 22151897_1 for this, we constructed a reporter plasmid bearing potential mir-494 binding sequences derived from the 3'-untranslated region of igf2bp1 mrna in the 3'-utr of the luciferase gene. 22151897_2 taken together, our present experiments suggest that the igf2bp1-igf2 axis could be a pivotal downstream targetfor mir-494, and this regulation could partly account for observed phenotypes of mir-494 stably expressing, a549 cells. 22151897_3 figure 2.downregulation of igf2bp1 in a549 cells expressing mir-494. in addition, we present evidence that igf2bp1 could be a target of mir-494. 22151897_4 notably, decreased igf2bp1 mrna levels in mir-494 stably expressing a549 cells accompanied stabilization of igf2 mrna, a downstream target of igf2bp1. 15522088_1 these data are consistent with a role for hfq in stabilization of sgrs, and also in facilitating the sgrs-ptsg interaction that mediates ptsg post-transcriptional regulation.the 15522088_2 region of complementarity occurred near the 3'end of sgrs and near the ribosome binding site of the ptsg mrna. 25423566_2 there were statistically significant differences in the expression of mir-219-5p with regard to sex, tumor size, and lymph node metastasis in patients with ptc. 25423566_4 further study showed that estrogen receptor alpha was the direct target of mir-219-5p and mediated the effect of mir-219-5p on ptc occurrence. 25423566_5 expression of mir-219-5p was inversely correlated with that of eralpha. 25423566_6 importantly, eralpha overexpression in ptc cells rescued the inhibitory effect of mir-219-5p on ptc cell proliferation and migration. 26498360_2 further investigation revealed that huwe1 was a direct target of mir-542-5p, and that reduced expression of this protein played an important role in the tumor-promoting effect of mir-542-5p overexpression. 18676839_1 in cell culture, e2f1 and p21/waf1 were identified as target of mir-106b, bim of mir-32, and exportin-6 and protein tyrosine kinase 9 of mir-1. 18676839_2 the protein expression of e2f1 and p21/waf1 was not influenced by mir-32 nor was the protein expression of bim influenced by mir-106b in these cell lines . 18676839_3 e2f1 and bim are direct target of mir-32 and mir-106b. 22723956_1 by combining in vitro and in silico approaches, we identified stat3 and rap1a as direct target that mediate the effect of mir-337-3p on paclitaxel sensitivity. 22723956_3 these results suggest that mir-337-3p has a general regulatory effect on stat3 and rap1a expression in lung cancer cells. 22723956_4 as shown in figure 3b, mir-337-3p over-expression significantly decreased luciferase activity in cells expressing the wildtype 3'-utrs as compared with no 3'-utr or mutated 3'-utrs, demonstrating that mir-337-3p interacts directly with specific sites in the 3'-utrs of stat3 and rap1a. 26041820_1 he tumor suppressor rassf1a is a direct target of the mir-181a/b cluster. 26041820_2 to validate our finding that rassf1a is a direct target of mir-181a/b, we analyzed rassf1a protein after mir-181a and mir-181b mimic transfection in u937 cells and observed repression of rassf1a protein 24 hours and much stronger 49 hours after transfection. 26323677_1 our findings demonstrate that mir-181a expression in lung adenocarcinoma is associated with emt progression, potentially through targeting of pten. 26323677_2 we determined that mir-181a responds to chemotherapy by changing the levels of its target pten. 26323677_3 overall, these results suggest that mir-181a inhibits the protein expression of pten by directly targeting 3'utr of pten. in this study, we found that mir-181a negatively regulates pten expression in lung adenocarcinoma cell lines. 20566844_1 expression of mir-29a or mir-29b significantly decreased luciferase expression of the construct containing the 3 ' utr of pxdn , whereas no significant effect was observed for bcl7a and itih5 . 20566844_2 thus, we concluded that pxdn expression could be targeted by mir-29. 20566844_3 these experiments revealed that coexpression of pxdn with mir-29a or mir-29b almost completely inhibited pxdn expression . 20566844_4 we therefore concluded that mir-29a and mir-29b targetpxdn expression at mrna and protein levels. 21787766_1 we conclude that mir-196 can fine-tune the anterior expression border of hoxb5a, hoxb5b, hoxb6b, and hoxc6a either as direct targets or because they are downstream of a mir-196 target. 18794369_2 using a previously described allele-specific quantitative rt-pcr technique , we demonstrated that downregulation of the 91h rna by sirna leads to a decrease of igf2 expression exclusively on the paternal apai allele . 20657826_1 in addition, it was found that mir-202-3p functionally decreases ppargc1a mrna in vitro. in any event, the microrna mir-202-3p experiment functionally confirmed a decrease ppargc1a mrna levels in cultured cells. 23711961_1 these data suggest that lpa1 is a target of mir-23a and that mir-23a mediates lpa-induced hypertrophy, in part through lpa1 suppression. 21541331_1 both jmjd1a and bach1 were the direct target of mir-155. 21541331_2 this shows that mir-155 directly target the jmjd1a and bach1 3'-utr leading to decreased expression . 21541331_3 densitometry analysis showed that both jmjd1a and bach1 expression were decreased by mir155 mimic in np69 cells . 21541331_4 densitometry analysis showed that jmjd1a expression was decreased by mir155 overexpression in cne1 and tw03 cells, while jmjd1a expression was increased by inhibition of mir155 . 26359097_3 mir-199a-5p inhibits the proliferation of rat airway smooth muscle cells and the expression of hypoxia inducible factor 1 alpha under hypoxia conditions. 26530100_1 luciferase assay revealed that cox-2 was a direct target for mir-101-3p and overexpression of mir-101-3p decreased cellular cox-2 protein expression. 26530100_2 furthermore, the level of cox-2 protein in eca109 cells significantly increased under the stimulus of 0.25% cse for 48 h, and attenuated by mir-101-3p overexpression , indicating cox-2 is a direct target of mir-101-3p under low concentration of cse. in the present study, we confirmed that the proliferation of eca109 cells when exposed to low concentration of cse was dependent on suppression of mir-101-3p and upregulation of its target cox-2 , yet this effect was not found in het-1a cells, indicating mir-101-3p may function as a tumor suppressor in the escc development but not in the initiation stage. 25547151_1 based on a computational search identifying znrf3 as a potential target of mir-146b-5p, we examined its levels of expression in the same ptc tissue samples by real time pcr and found significantly lower levels of znrf3 mrna in tumors with lnm than in those without . 25547151_2 a scatter diagram confirmed that mir-146b-5p expression and znrf3 expression are negatively correlated . 25547151_3 znrf3 is a target of mir-146b-5p in ptc. 25547151_4 these results indicated that mir-146b-5p promotes the migration and invasion of ptc cells by downregulating the expression of znrf3. 25547151_5 these results indicated that mir-146b promotes emt in ptc cells by downregulating the expression of znrf3. 26158900_2 these combined results strongly suggest that mir-17 directly targets etv1 by translational repression. 26158900_3 mir-17 is a direct translational repressor of etv1. 26715733_1 specifically, we have found that rock1 is a direct and functionally relevant target of mir-584- 3p in glioma cells. 26715733_2 further investigation using glioma cell lines and orthotopic implantation of tumors into a nude mouse model revealed that mir-584- 3p reduced the migratory and invasive abilities of glioma cells by targeting the hypoxia-induced kinase rock1. 26715733_3 these results demonstrate that rock-1 is a direct target of mir-584- 3p. 26868958_2 ano1 as possible target of mir-132. 25356754_1 mir-29b inhibited its downstream effectors of pik3r1 and akt3 through direct targeting their 3'-utr regions. in particular, we demonstrated by a variety of in vitro and in vivo approaches that phosphoinositide-3-kinase regulatory subunit 1 and protein kinase b are direct targets of mir-29b in hscs responsible for signaling onset of hscs activation and liver fibrosis. 25356754_2 whist mir-133a had no inhibition effect on the reporter activity of the mutant 3'-utr of pik3r1 and akt3 ,6b, indicating the direct regulation of mir-29b at the 3'-utr of pik3r1 and akt3 transcripts. 25356754_3 ectopic expression of mir-29b remarkably reduced protein expression of pik3r1, akt3 and phosphorylated akt in both cell lines ,6c, suggesting that pik3r1 and akt3 are bona fide targets of mir-29b. 22545247_1 mir-146a-mediated regulation was cell-intrinsic and depended on relb, a member of the noncanonical nf-kb/rel family, which we identified as a direct mir-146a target. 22545247_2 experimental evidence also indicates that relb is a mir-146a target. 22545247_3 these data indicate that mir-146a can control ly-6c hi monocyte fate in response to acute inflammatory challenge via relb targeting. 22545247_4 mir-146a in monocytes targets relb, which expression levels tune the amplitude of ly-6c hi monocyte responses. 22249219_1 microarray and reporter gene assays revealed that a2ar expression is controlled by mirna-214,mirna-15, and mirna-16. 22249219_2 these results indicate that mirna-214, mirna-15, and mirna-16 are regulators of a2ar expression, whereas mirna-342-3p is not. 22249219_3 these data demonstrate that these mirnas regulate a2ar expression by directly targeting the specific binding sites within the gene's 3'-utr. in pmns, the increase in a2ar mrna expression upon stimulation was inversely correlated with the expression levels of mirna-214, mirna-15, and mirna-16 . 18381414_2 the statistically significant reduction of luciferase activity was observed in na cells cotransfected with mir-137 and a reporter vector containing the cdk6 3'-utr targetsite and those cotransfected with mir-193a and a vector containing the e2f6 3'-utr targetsite compared with control transfectants. 18381414_3 no notable alteration of luciferase activity was detected between mir-137 or mir-193a transfectant and control counterpart in other genes. 21698760_2 the results showed that mir-200a blocking could enhance egfp expression, and ectopic expression of mir-200a could reduce the intensity of egfp fluorescence . 21698760_4 these results suggested that mir-200a could directly bindto the 3'-utr of thbs1 mrna and specifically suppress targetgene expression. in contrast to the controls, knockdown of mir-200a in huvecs resulted in a significant increase of thbs1 mrna and protein levels , whereas overexpression of mir-200a reduced thbs1 mrna and protein level . 21698760_5 these results indicated that mir-200a could reduce thbs1 expression through both translation inhibition and rna degradation. 23747307_2 small interfering rna and mir-us25-2-3p mediated eif4a1 knockdown experiments revealed that high level of mir-us25-2-3p in mrc-5 cells decreased hcmv and host genomic dna synthesis, and inhibited cap-dependent translation and host cell proliferation. 23747307_3 however, eif4a1 up-regulation induced by mir-us25-2-3p inhibitor increased hcmv copy number. 26487539_1 we found that mir-129 overexpression reduced cp110 expression at both the mrna and protein level, whereas transfection of the mir-129-3p inhibitor increased cp110 expression in breast cancer cells . 26487539_2 taken together, these results strongly suggested that cp110 is a direct mir-129-3p target in the breast cancer cells 20459811_2 finally, transcriptome analysis of mir-146a overexpression in t cells identified fas associated factor 1 as a mir-146a-regulated gene, which was critically involved in modulating t cell apoptosis. 26096707_1 accordingly, mir-21 inhibition resulted in the reduction of mir-21 target genes expression and also in a significant decrease of acta4. 25213330_1 mir-193b targets fasn and kills breast cancer cells, but not normal cells 26901347_1 mir-221 regulated il-4 levels in the supernatants of p815 cells. 23201690_1 full tincr binding to the pglyrp3 differentiation gene mrna occurred with or without stau1 protein, but was dependent on the 3'pglyrp3 tincr box . 23201690_2 stau1 protein displayed the strongest tincr rna binding . 23201690_3 gene set enrichment analysis 26 of sistau1 as well as sitincr gene sets showed marked overlap with the keratinocyte differentiation signature published previously indicating that tincr together with stau1 is required for epidermal differentiation. 23201690_4 binding of tincr to interacting mrnas occurs through the tincr box motif. 23201690_5 loss of the tincr-associated cytoplasmic protein stau1 resembles tincr loss and demonstrates a new upf1/2-independent role for stau1 in differentiation. 26349993_1 mir-214 mimic down-regulated expression of -beta-synuclein and its 3'-utr activity, while the levels were up-regulated by mir-214 inhibitor. 26349993_2 in addition, the cell viability, elevated by resveratrol, was also decreased by mir-214 inhibitor or overexpressed -beta-synuclein. in vivo, mir-214 inhibitor down-regulated th+ cells of ipsilateral and up-regulated -beta-synuclein expression compared with the group treated with resveratrol. 26160036_1 taken together, the results show that mir-495 regulates the gfi1 levels by translational suppression rather than by mrna degradation. 26160036_2 our study provides the first demonstration that mir-495 directly interacts with the gfi1 3'-utr to regulate gfi1 at a post-transcriptional level and that the expression level of mir-495 is inversely correlated with the gfi1 protein level in medulloblastoma specimens. 22662276_2 thus, mir-34a up-regulation in tumors has an anti-angiogenic effect potentially mediated through direct inhibition of mycn. 21799909_1 co-transfection of pre-mir over-expression constructs for mir-494 and mir-142-3p in hek293 cells had significant effects in repressing luciferase-reported bmal1 3' utr activity by as much as 60%, suggesting that these mirnas may function as post-transcriptional modulators of bmal1. 21799909_2 transfection with a non-targeting mirna had no significant effect on luciferase-mediated bioluminescence in bmal1 3- utr-expressing cells relative to that found in cells transfected with the control vector, suggesting that basal reporter activity is similar between the bmal1 3- utr and control vectors and that the observed repression of the bmal1 3- utr is specific for mir-494 and mir-142-3p. 21799909_3 based on the independent and combinatorial effects of mir-494 on bmal1 3- utr activity, our results support the possibility that oscillations in serum levels of this mirna may contribute to local rhythms in the post-transcriptional repression of endogenous bmal1 in the periphery. 21854740_1 luciferase reporter assays assessed functional binding of mir-666 and mir-708 to the untranslated region of aqp1 ; consistent with the pcr studies, mir-666 showed a larger and statistically significant effect size. 21854740_2 figure 7 mir-666 and mir-708 functionally bind the utr of aqp1. 26790956_1 an inverse correlation was observed between spag9 and mir-141 expression in hcc tissues and cell lines. 26790956_2 dual-luciferase reporter assay further showed that spag9 was a direct target gene of mir-141. 26790956_3 the ectopic expression of mir-141 could markedly suppress spag9 expression in hcc cells. 26790956_4 mir-141 overexpression also resulted in significantly reduced cell proliferation, invasion, and migration, and imitation of the spag9 knockdown effects on hcc cells. 26790956_5 furthermore, spag9 restoration in mir-141-expressing cells sufficiently attenuated the tumor-suppressive effects of mir-141. 26790956_6 finally, jnk activity was found to be reduced by mir-141 overexpression the same way as by spag9 silencing. 26790956_7 the overexpression of spag9 lacking its 3'-utr significantly restored jnk activity and its downstream genes in mir-141-transfected hcc cells. 22059741_1 mir-1 directly target ptma gene. 22059741_2 all data indicate that mir-1 impairs ptma mrna expression by directly binding to the ptma mrna 3'-utr in npc-tw01 cells. 22059741_3 figure 4 luciferase assay demonstrates that mir-1 directly target ptma 3' utr. 22059741_4 ptma is one of mir-1 targetgenes that involve in apoptosis. 22570426_1 mir-181d: a predictive glioblastoma biomarker that downregulates mgmt expression. 22570426_3 luciferase reporter assays and coprecipitation studies showed a direct interaction between mir-181d and mgmt 3'utr. in the remaining 11 specimens, the mgmt transcript level was inversely correlated with mir-181d expression. 22570426_4 given the results suggesting that mir-181d post-transcriptionally regulates mgmt, we anticipated an inverse correlation between mir-181d expression level and mgmt transcript level in glioblastoma specimens. 22570426_5 together, these results provide evidence that mir-181d directly interacts with mgmt transcript to downregulate its expression. 23553486_1 suggesting a posttranscriptional regulation of p27 by mir-24. 23553486_2 these results demonstrate that mir-24 is able to directly targetboth p27 and p16, and thus to regulate the expression of the main cdkis. 23553486_3 we demonstrated that mir-24 negatively regulates p27 and p16 protein levels either in normal keratinocytes and in tumor derived cell lines. 23553486_4 our results demonstrate that the concomitant downregulation of p27 and p16 in mir-24-overexpressing heka cells leads to an increase of the proliferation rate, by inducing a g1 to s shift in the cell cycle. 26542138_1 the luciferase expression levels of samd4b, cadm4, rtp3, and tmem54 were lower than the controls a-d , except for that of sp5 . 20624000_1 we observed that the micrornas mir-221/222 are associated with apoptosis regulation under er stress in human hepatocellular carcinoma cells. in these cells, er stress-induced apoptosis is enhanced by mir-221/222 mimics and attenuated by mir-221/222 inhibitors. 20624000_2 mir-221/222 promoted-apoptosis under er stress is associated with p27 - and mek/erk-mediated cell cycle regulation. 23019365_1 the luciferase assay was used to test the interactions between these mirnas and creb 3- utr, and we found that mir-124 and mir-128 but not mir-181b repressed the activity of creb 3'-utr luciferase reporter . 25978641_1 to demonstrate efficacy of tiny lnas, hek293 cells, transfected with pfgf9 utr and mir-140 or mir-328 mimics, were co-transfected with tiny lna antagomers. 25978641_2 at a concentration of 10 nm, tiny lnas effectively blocked mir-140 or mir-328 ability to suppress fgf9 3- utr activity in vitro . 26554847_1 altogether, these results suggest that abcb5 is one of the targets for mir-340-5p which is down-regulated in melanoma cells grown in hypoxic conditions 22824797_1 microrna-125b promotes apoptosis by regulating the expression of mcl-1, bcl-w and il-6r. 22095944_2 conversely, where the mir-29 binding sites were mutated in the collagen i and iv 3'-utrs so that mir-29a/b/c could no longer binduciferase activity was unaltered by mir-29a/b/c . 22095944_3 these data confirm that the mir-29 family is a specific and potent translational repressor of collagen i, iva1, and iva3 by targeting the 3'-utr of these genes and thus can override the profibrotic effect of tgf--beta1 on these genes. 21385848_1 these results indicate that silencing of c-fos expression by mir155 is a conserved process that is required for dc maturation and function. 21385848_2 among the target mrnas that were up-regulated in mir155 / bm-dcs , only c-fos mrna was reduced in dc2114 cells overexpressing mir155 . 21385848_3 the fact that c-fos protein was increased to a greater extent than c-fos mrna suggested that mir155 represses c-fos expression mainly at the level of translation. 21385848_4 these results confirmed that the predicted mir155-binding sites in the 3'-utr of c-fos mrna were indeed targeted directly by mir155. 26318860_1 interestingly, tug1 decreased the expression of mir-145 and there was a reciprocal repression between tug1 and mir-145 in an argonaute2-dependent manner. 26318860_2 taken together, these data suggested that mir-145 could directly bind to tug1 and negatively regulated tug1 expression. 26318860_3 these data indicated that both tug1 and mir-145 are probably in the same risc complex, consistent with our bioinformatic analysis and luciferase assays. 26318860_4 luciferase assay indicated that mir-145 could bind to tug1 directly by the putative mirna response element. 26318860_5 finally, we found that tug1 and mir-145 were in the same risc complex by rip assays, suggesting that there was a physical interaction in bladder cancer cells. in addition, we demonstrated that tug1 negatively regulated mir-145 expression by acting as a mirna sponge. 24804790_1 upregulation of mir-101 expression could inhibit trophoblast htr-8/svneo cell apoptosis and repress er stress-induced apoptotic proteins by targeting erp44 in vitro, whereas inhibition of mir-101 could induce htr-8/svneo cell apoptosis. 22469780_1 in addition, overexpression of mir-125b protected pre-bi and leukemic b-cell lines from apoptosis by blockade of caspase activation by a mechanism that was independent of p53 and bak1.mir-125b 19916867_1 overexpression of mir-513 through transfection of mir-513 precursor inhibited c. parvum-induced b7-h1 protein expression. 19916867_3 the apoptosis of activated t cells was partially blocked by a neutralizing antibody to b7-h1 or transfection of cholangiocytes with mir-513 precursor. 19916867_4 these data suggest a role of mir-513 in regulating b7-h1 expression by cholangiocytes in response to c. parvum infection. 23104321_1 our data verified that mir-143 directly targeted akt in t24 cells and that mir-145 indirectly regulated akt expression. 23104321_2 we newly elucidated that mir-143 targeted akt and that mir-145 targeted integrin-linked kinase in t24 cells based on the results of a luciferase activity assay. 20525681_1 these data provided a strong rationale to test our hypothesis of whether gsk-3-beta is functionally a downstream target of mir-26a in the hypertrophic pathway of hasmcs. 20525681_2 overall, these data provided experimental evidences demonstrating that gsk-3-beta is a targetgene of mir-26a. 20525681_3 overall, our data support a model in which mir-26a participates in hasmc hypertrophy by suppressing gsk-3-beta protein expression, which in turn triggers the expression of smooth muscle-specific markers and hypertrophy . 18593897_2 moreover, we observe that mir-206 expression is inversely correlated with eralpha but not erbeta mrna expression in breast cancer tissues. 18593897_4 our results suggest that mir-206 could be a novel candidate for endocrine therapy that targets only eralpha in breast cancer. 24814047_1 tumor suppressor p53 induces mir-1915 processing to inhibit bcl-2 in the apoptotic response to dna damage. 26546816_1 identification of the conservation mir-134 target site with the 3'utr of angptl4. 26546816_2 taken together, these data suggested that angptl4 was a specific target of mir-134. 26546816_3 angptl4 is a functional target of mir-134 and participates in the regulation of lpl protein and activity. 22003227_1 to assess mir-137-mediated modulation of ezh2 and mitf mrna levels, we monitored transcript levels in lcl of our patients and healthy controls by qrt-pcr. 22003227_2 this investigation revealed significantly increased mitf and ezh2 levels in the patients as compared to two healthy controls . 22003227_3 figure 4 validated mir-137 targets mitf and ezh2 mrna levels are increased in the patients. 20634564_2 overexpression of mir-181a and b, mir-9, mir-204, mir-135a, and mir-199b decreased sirt1 protein levels in mescs . 20634564_3 these data confirm that mir-181a and b, mir-9, mir-204, mir-135a, and mir-199b target endogenous sirt1 and downregulate its expression. 20634564_4 thus, of the 17 mirnas upregulated during mesc differentiation that potentially target sirt1, mir-9 acts early during differentiation to downregulate sirt1 expression. 20634564_5 these observations confirmed that mir-9 inhibition increased sirt1 protein levels. 26482776_1 furthermore, we found that there was reciprocal repression between malat1 and mir-1, and slug was identified as a downstream target of mir-1. 26482776_2 these data suggested that the mir-1 binding sites within malat1 were functional. 26482776_3 these data suggested that both malat1 and mir-1 are probably in the same risc complex. 26482776_4 taken together, these data indicated that by binding with mir-1, malat1 acted as a cerna for the target slug mrna, thereby modulating the de-repression of slug. 19098914_1 the functional consequence of this downregulation for kshv latency can be assessed by examining the effects of bclaf1 modulation on viral replication. 19098914_2 when latently infected cells are chemically induced to lytic kshv growth, antagonism of mirs k5,9, 10a and 10b is associated with decreased virion production and increased bclaf1 expression . 19098914_3 this suggests that bclaf1 action acts to impair lytic viral replication. 22470493_2 we finally confirmed that stmn1 is a putative downstream target of mir-223 in gastric cancer. 22470493_3 tumors with higher stmn1 immunoreactivity showed a non-significant trend towards a lower mir-223 expression level. 22470493_4 the negative modulation effect by mir-223 was further substantiated by a significantly reduced stmn1 protein level in gastric cancer cell lines after mir-223 re-expression. . in this study, we observed a low mir-223 expression level in gastric cancer cell lines and an inverse relationship between mir-223 and stmn1 protein expression. 19786632_3 furthermore, we used a sirt1 3'-utr luciferase reporter vector to explore the effect of mir-217 on expression of sirt1 mrna. 19786632_4 cotransfection of pre-mir-217 , which mimics mature mir-217, with sirt1 3'-utr reporter in hek293 cells resulted in 40% inhibition of luciferase activity compared with samples transfected with the control oligonucleotide . 19786632_5 gene-expression studies revealed that mir217 was also able to downregulate sirt1 and foxo1 target in hcaecs . 26463627_2 luciferase reporter assay showed the decreased smad7 3'-utr activity in rgc-5mir-187mimic and the increased smad7 3'-utr activity in rgc-5mir-187inhibitor 22698995_1 let-7 mirna directly down-regulates bach1 gene expression at a post-transcriptional level in huh-7 and hepg2 cells. 22698995_2 the let-7 microrna enhances heme oxygenase-1 by suppressing bach1 and attenuates oxidant injury in human hepatocytes. 22698995_3 in conclusion, let-7 mirna directly acts on the 3'-utr of bach1 and negatively regulates expression of this protein, and thereby up-regulates hmox1 gene expression. 22698995_4 the effects of let-7 mirna on bach1 and hmox1 gene expression in huh-7 and hepg2 cells were determined by real-time qrt-pcr, western blot, and luciferase reporter assays. 22698995_5 table 1 computational analysis of bindsg sites for let-7a, let-7b, let-7c, let-7e and mir-98 in the 3'-utr of bach1 mrna. 22698995_6 these results demonstrated that let-7b, let-7c and mir-98 directly targetbach1 3'-utr. 22698995_7 as expected, mutant let-7b resulted in a significant reduction in let-7b, let-7c mutant reporter luciferase activity, whereas let-7b did not affect mutant reporter luciferase activity , further indicating the direct interaction between let-7 mirna and the 3'-utr of bach1 mrna. 22698995_8 let-7a, let-7c and let-7e inhibitors significantly up-regulated bach1 protein levels in comparison to negative controls in huh-7 cells without affecting bach1 mrna levels . 20153722_1 western analysis demonstrated that pten, a known target of mir-21, was downregulated in huvecs exposed to uss or transfected with pre-mir-21. 20153722_2 importantly, huvecs overexpressing mir-21 had decreased apoptosis and increased enos phosphorylation and nitric oxide production. 26722242_2 it was found that mir-133b suppressed gbm cell migration and invasion, and matrix metalloproteinase 14 was identified as a direct target gene. 26722242_4 these findings demonstrated that the 3'-utr of mmp14 was the directed target of mir-133b. 22217655_2 2b, mir-195 significantly suppressed the expression of the renilla luciferase reporter carrying the wild-type putative target sites of ccnd1 , ccnd3 , and e2f3 , compared with controls , suggesting that all 3 genes contain effective mir-195 binding sites in their 3'-utrs. 22217655_4 these data suggest that ccnd3 and e2f3 may be functional targets of mir-195 in glioblastoma cells. 22217655_5 these data indicate that e2f3 is likely to be the dominant target of mir-195 in regulating glioblastoma cell cycle progression , whereas ccnd3 may be involved in regulating different aspects of glioblastoma cell behavior. 26539909_1 real-time pcr analysis and northern blotting assay showed that the expression of nlc1-c was significantly inhibited by mir-320a/mir-383 mimics and was promoted by mir-320a/mir-383 inhibitors . 26539909_2 while, as shown in supplementary figure s5a and b, the expression of nucleolin mrna and protein level was not affected by mir-320a/mir-383 mimics and inhibitors. 26539909_3 taken together, these results demonstrate that nlc1-c is a direct target of mir-320a and mir-383. 26539909_4 these results demonstrate that nucleolin binding to nlc1-c co-regulates mir-320a and mir-383 transcription mediating the increase of nlc1-c expression induced by nucleolin. 21807947_1 there appears to be a possible link between mir-199a-3p, caveolin-2 and cdc42, which is that mir-199a-3p might be involved in regulation of cell proliferation, survival and cell migration by directly targeting caveolin-2, which then upregulates cdc42 expression to exert the biological functions of mir-199a-3p. 21807947_2 this reversed co-relationship suggests that mir-199a-3p has roles in repressing caveolin-2 expression in these cell lines. 21807947_3 these results suggest that caveolin-2 has an important role in mediating the effect of mir-199a-3p on cell activities. 26124189_2 mir-181a-5p down-regulates kras expression by directly targeting its 3'-utr. 23394580_1 these findings demonstrated that mir-200c is a repressor of tubb3 expression in a2780 cells through an interaction in the 3'-utr of the gene, as described previously by cochrane and colleagues in hey cells. 23394580_2 suggesting that mir-200c was capable to inhibit the overexpression of tubb3 gene under stressing conditions. 23394580_3 overall, these results suggested that a2780 and ovcar-3 cell lines represent two different models, and prompted us to investigate the mechanism of mir-200c in regulation of tubb3 expression, analyzing the involvement of additional factors. 25689721_1 ursolic acid inhibits the glucose-induced up-regulation of mesangial cell mirna-21 expression, up-regulates pten expression, inhibits the activation of pi3k/akt/mtor signaling pathway, and enhances autophagy to reduce the accumulation of the extracellular matrix and ameliorate cell hypertrophy and proliferation. 26159098_1 our results identify rabgef1 as an additional candidate target of mir-124 in the signaling pathway 26589846_1 collectively, these data provide evidence that mir-181a regulates autophagy through targeting of atg5. 26589846_2 fig. 2. mir-181a affected atg5 expression in sgc7901/cddp cells. 19584290_1 mir-29a directly target b7-h3 3'utr and down-regulates b7-h3 protein expression. 19584290_2 over-expression of mir-29a in nb1691 substantially reduced b7-h3 protein expression with a reduction of ~60% when compared with negative control . 19584290_3 b7-h3 mrna level was not affected , suggesting that modulation of b7-h3 protein levels by mir-29a was primarily due to repressed translation, and not mrna degradation. 19584290_4 all these data suggest an inverse correlation between b7-h3 protein and mir-29 expression level. 19584290_5 these results suggest that complementary site in the b7-h3 3'-utr is a direct target of mir-29a mediated posttranscriptional gene silencing. 19584290_6 these data provide direct evidence that mir-29a targeted b7-h3 mrna and was able to modulate b7-h3 protein expression. 26479438_2 mir-185 repressed the 3'-utr activity of agpat3, ldlr, scd1 and srebp2. 26479438_3 this inhibition was alleviated through mutation of the predicted mir-185 binding sites , confirming the direct interaction of mir-185 with the 3'-utr of these genes. 26479438_4 scarb1 was also previously validated as being directly regulated by mir-185 . 26479438_5 similarly, mir-130b was also found to directly regulate ldlr and was previously validated as a direct regulator of ppar纬33 . 24400442_1 modulation of let-7c altered the sensitivity of a549/ddp cells to ddp through regulating ddp-induced apopotis. 24400442_2 furthermore, abcc2 and bcl-xl were identified as targets of let-7c. 22089643_1 furthermore, transient transfection of mir-133a, repressed arpc5 and gstp1 mrna and protein levels. 22089643_2 we performed gain-of-function studies using mir-133a transfectants, and the arpc5 and gstp1 mrna and protein expression levels were markedly downregulated in comparison with the controls . 26395400_1 mir-144 interacted with the oncogene zeb1 at 2 sites in its 3- untranslated region, and a decrease in mir-144 resulted in increased zeb1 expression and an epithelial mesenchymal transition phenotype. 26395400_2 ectopic expression of mir-144 suppressed nsclcs in vitro and in vivo by targeting zeb1. in contrast, transfection of anti-mir-144 into the cells resulted in up-regulation of the zeb1 protein , suggesting that zeb1 could be a target gene of mir-144. 26395400_3 we showed that zeb1, a tran- scriptional repressor 42 that inhibits e-cadherin and promotes emt and metastasis 12,43 , is a target of mir-144. 23549102_1 serum mir-134, mir-320c and mir-483-5p were significantly upregulated during hcv infection. 23549102_2 mir-320c and mir-483-5p were also upregulated in hcv- jfh1 infected cells and cell culture supernatant. in case of mir-483-5p, validated targets included srf a modulator of vegf signaling and erk1 a member of the ras-erk intracellular signaling pathway that is modulated by hcv proteins such as ns5a. 26432591_1 previously mir-31-5p has been studied in the regulation of the expression of human mutl homologue-1 . 26432591_3 to further understand the radioprotective effect of the mir-31-5p inhibitor, cellular expression levels of the human mutl homolog 1 was assessed by western blot analysis.hmlh1 26432591_4 is one of the core dna mismatch repair genes,defective in a subset of colon cancer patients and is a direct target of mir-31-5p. 26432591_5 while mrna levels of hmlh1 was decreased with the mir-31-5p mimic , there was no significant decrease in protein levels of hmlh1 in hcec ct7 and dld1 colon cancer cell. 26432591_6 these data further support that hmlh1 is a critical downstream effector protein that is involved in modulation of radiosensitivity by mir-31-5p after ir. 25159729_1 overexpression of mir-223 decreased fbxw7 expression and the sensitivity of gc cells to trastuzumab, while suppression of mir-223 restored fbxw7 expression and the sensitivity of gc cells to trastuzumab. 26800097_1 mechanistically, it was revealed that mir-146a modulated macrophage polarization by targeting notch1. 26800097_3 thus, the data demonstrated that in addition to inhibiting notch1, mir-146a may drivethetransitionofmacrophage polarization towardm2 phenotype by activating ppargamma. 26800097_4 clearly,the hypothesis was verified by our results that mir-146a repressed the m1 macrophage switch and promoted m2 macrophage polarization via inhibiting notch1. 26848028_1 it was also demonstrated that wingless-related mmtv integration site 4 was a target of mir-29c, determined using bioinformatic analysis combined with luciferase assays. 26848028_2 these results indicated that the 3'-utr of wnt4 either contains mir-29c binding sites or that wnt4 is a target of mir-29c. 26848028_3 furthermore, wnt4 mrna was revealed as a target of mir-29c, thereby regulating the wnt/ -beta -catenin signaling pathway and modulating cardiac development. 22153071_1 our approach resulted in the identification of two micrornas, mir-24 and mir-629 as direct regulators of hnf4alpha expression. 22153071_2 several lines of evidence indicate that mir-24 and mir-629 targethnf4alpha directly, binding to its 3'utr. 22153071_3 sequence complementarity analysis revealed that hnf4alpha is a gene target of mir-24 and mir-629, and upon overexpression of mir-24 or mir-629, hnf4alpha mrna levels are reduced 5-fold and 2-fold, respectively . in addition, hnf4alpha protein levels drop , and the direct downstream target are down-regulated by mir-24 and mir-629 . in addition, combined expression of these two mirnas resembles the effects of hnf4alpha knockdown . 18523662_1 mir-320 played an important role for the down-regulation of its target gene, cd71 during reticulocyte terminal differentiation. 18523662_2 further investigation revealed that poor expression of mir-320 in hbss cells was associated with their defective downregulation cd71 during terminal differentiation. 21934092_1 we identified foxo4 and pdcd4 as direct and functional target of mir-499-5p. 21934092_3 these findings suggest that the prometastatic function of mir-499-5p in crc may be attributed to a suppressive effect on foxo4 and pdcd4 expression. 21934092_4 this finding supported the hypothesis that foxo4 and pdcd4 expression were inversely associated with mir-499-5p expression in crc cells. 21934092_5 these data confirmed that the prometastasis effect of mir-499-5p was mediated by inhibiting targetgenes foxo4 and pdcd4. 21934092_6 additionally, we identified foxo4 and pdcd4 mrna as direct and functional target of mir-499-5p. 19336275_1 to determine the potential roles of mirnas in h o -mediated gene regulation and cellular injury, mir-21 expression was downregulated by mir-21 inhibitor and upregulated by pre-mir-21. 19336275_2 h o -induced cardiac cell death and apoptosis were increased by mir-21 inhibitor and was decreased by pre-mir-21. 19336275_3 programmed cell death 4 that was regulated by mir-21 and was a direct target of mir-21 in cardiac myocytes. 26854484_1 our data further support foxp1 as a target of mir-34a, suggesting that downregulation of foxp1 may sensitize dlbcl cells to doxorubicin. 26637059_1 to further elucidate the mechanism of mir-26b-5p participation in the regulation of elf-emfs, we identified the potential target genes of mir-26b-5p. 26637059_2 these results suggest that mir-26b-5p can regulate the expression of ccnd2 by directly targeting its 3'-utr. 26637059_3 mir-26b-5p overexpression were strongly attributed to the mrna expression of ccnd2. 21479367_1 we, therefore, confirmed that mir-145 can impair the proliferation of human lung adenocarcinoma-initiating cells by targeting oct4 and leads to inhibition of lung cancer development. 21479367_2 figure 6. mir-145 directly target oct4 mrna. 21479367_3 our data indicated that mir-145 regulates the expression of oct4 which may be one of the modulators of the cell growth and invasion. 25790935_1 we present novel evidence of the contribution of mir-301a to il-6-induced insulin resistance by direct regulation of pten expression. 25790935_2 our data demonstrate that mir-301a could regulate pten expression by directly binding to its 3'-utr. 25790935_3 in conclusion, we present novel evidence suggesting that mir-301a contributes to il-6-induced insulin resistance by directly regulating pten expression. 21359530_1 moreover, pten was shown to be a direct target of mir-29b and was also shown to contribute to the mir-29b-mediated effects on cell invasion. 21359530_3 6 expression of pten affected by mir-29b. 21359530_4 as a result, we speculate that other mrnas that may be targeted by mir-29b may serve to modulate the effect on pten. 20923760_1 we showed that mir-28 and mir-505 modulate asf/sf2 by directly binding asf/sf2 3'-utr. 20923760_2 inactivation of either mir-28 or mir-505 binding sites in the asf-utr significantly increases gfp expression, indicating a direct binding of these mirnas on asf/sf2 3'-utr . 20923760_3 mir-28 and mir-505 down-regulate asf/sf2 by directly binding its 3'-utr. 20923760_4 as expected, the overexpression of lrf increased asf/sf2 protein but not mrna and down-regulated the expression of mir-505 and mir-28 . 20923760_5 all these findings indicate that mir-28, mir-505, and asf/sf2 might be part of the lrf regulatory network. 22854067_1 furthermore, mir-31 target the 3'utr of rhoa and is able to down-regulate rhoa expression. 22854067_2 mir-31 target rhoa inhibiting the growth and migration of oscc cells. 22854067_3 the analysis showed that there was targeting by mir-31*, but not by mir-31, against the 3'utr of rhoa in this reporter construct . 22854067_4 western blot analysis exhibited a significant decrease in rhoa expression following up-regulation of either mir-31 or mir-31* . 22253433_1 these data indicate that mir-30a, -30b, -30c, and -30d appear to be involved in the preosteoblast differentiation of mc3t3-e1 cells induced by bmp-2. 22253433_2 furthermore, dual-luciferase reporter assays confirmed that smad1 is a direct target of mir-30 family members. 22253433_3 these results provide evidence that the mir-30 family negatively regulates smad1 and runx2 expression. 22253433_4 furthermore, quantitative rt-pcr assays demonstrated that smad1 mrna did not change in mir-30-overexpressing cells , indicating that mir-30 family members regulate smad1 gene expression on the basis of translational repression rather than mrna degradation. 22253433_5 these data provide strong evidence that mir-30 family members inhibit smad1 gene expression by directly binding to the two distinct seed sites within its 3- utr. 22253433_6 these results suggest that the early down-regulation of mir-30 expression, immediately after bmp-2 treatment, may facilitate releasing their suppression of smad1 and runx2 expression. 22253433_7 all of these data provide evidence that mir-30 members mediate the inhibition of osteogenesis by targeting smad1 and runx2. 26088024_1 we have previously shown that mir-22 binds to the 3'-utr of icam-1 mrna and that knockdown of mir-22 in hmec-1 causes de-repression of icam-1 gene expression. 26088024_2 as expected,the up-regulation of mir-22 at 3 h after treatment was followed by a reciprocal decrease in icam-1 expression at 24 h. 26088024_4 as shown in figure 3 c, overexpression of mir-22 caused a 20% reduction in cell surface-bound icam-1 , thus confirming our previous results and indicating that mir-22 plays a role in regulating endothelial icam-1 expression. 21085192_1 stimulation of sézary cells or healthy cd4+ t cells with the common--gamma chain cytokine il-21 results in a strong activation of stat3, and subsequent upregulation of mir-21 expression. 21085192_2 both pri- and mature mir-21 expression are increased in sézary cells when compared with cd4+ t cells from healthy donors. 21085192_3 silencing of mir-21 in sézary cells results in increased apoptosis, suggesting a functional role for mir-21 in the leukomogenic process. 23435373_1 taken together, these findings indicate that smad7 is a direct, downstream target for mir-25 in hct116 cells. 26806308_1 hmga1 was confirmed as a direct target of mir-625. 26806308_2 the expressions of hmga1 mrna and protein were induced by mir-625 mimics, but reduced by mir-625 inhibitor. 26806308_3 re-introduction of hmga1 in cells expressing mir-625 distinctly abrogated mir-625-mediated inhibition of cell growth. 26806308_4 taken together, our data demonstrate that mir-625 suppresses cell proliferation and migration by targeting hmga1 and suggest mir-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer. 26806308_5 these results demonstrated mir-625 directly binded to the 3'-utr of hmga1 and suppressed its expression in breast cancer. 26806308_6 collectively, our data suggest that mir-625 suppresses cell proliferation and migration by targeting hmga1. 25132116_2 to address this issue, we inserted microrna response elements of mir-133a, mir-137 and mir-449a, which are all underexpressed in lung cancer cells, into an adenoviral vector to regulate trail expression. 22205749_1 mir-27b inhibits viral replication via the direct targeting of cyclin t1 mrna and, along with mir-29b, mediates the targeting of cyclin t1 mrna to the risc. 22205749_2 this finding indicated that the four residues mutated within the cyclin t1 3'-utr are necessary for mir-27b binding, as the disruption of this site abrogates the mir-27b-mediated inhibition of luciferase expression. 26160841_1 we firstly confirmed that ectopic expression of mir-21 mimics effectively downregulated pias3 in hs-5 cells and next, we evaluated the effects of mir-21 inhibition. 26160841_2 indeed, pias3 expression was increased at both mrna and protein levels in cells transduced with mir-21 inhibitors in all co-culture systems. 21763111_1 the respective targets of mirna-21 and -106a, the tumor suppressors pten, pdcd4 and rb with their pivotal role in cell cycle regulation, apoptosis and proliferation were found to be downregulated. 25053820_1 mir34a is a tumor-suppressor mirna that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. 25477702_1 functional analyses showed that upregulation of mir-127 significantly inhibited growth, enhanced apoptosis, and reduced migration and invasion in bc cells by targeting the protooncogene bcl-6. 25477702_2 therefore, mir-127 may be a potential biomarker for predicting the survival of bc patients and might be a molecular target for treatment of human bcs. 15504739_3 in addition, protein levels of the proposed mir-143 target erk5 were higher in aso-treated adipocytes. 24832599_1 in this study, we validate and report that mir-374a and mir-548b modulated by axl have essential roles in cell cycle arrest, gefitinib-induced apoptosis, epithelial-to-mesenchymal transition, migration and tumorigenesis of gefitinib-resistant lung cancer cells in vitro and in vivo by targeting wnt5a and ccnb1 genes, respectively. 25831148_1 in contrast, mir-95 has been reported to induce proliferation and chemo- or radioresistance through directly targeting sorting nexin1 and sphingolipid phosphatase 1 in nsclc . 25831148_2 mir-21 expression has been demonstrated to promote tumor growth, metastasis, and chemo- or radioresistance in nsclc cells by targeting pten . 25831148_3 results showed that mir-21 and mir-95 mrna levels were significantly decreased in tumors in the groups treated with cpnp-anti-mirna injection alone and combination of radiation and cpnp-anti-mirna injection . 25831148_5 targeting inhibition of mir-21 and mir-95 can inhibit tumor growth through elevating pten, snx1, and sgpp1 expression and inhibiting pi3k-akt signaling. 22072622_2 western blot analysis revealed that the levels of tgf-betar2, pdcd4 and pten, the target of mir-21 , were decreased in mir-21 overexpressing clone 1 as well as in pooled clone as compared with vector-transfected controls . 22072622_3 fig. 4.the putative mir-21 binding to tgf-betar2-3'-utr is responsible for mir-21-mediated downregulation of luciferase activity. 22072622_4 the results from the current investigation show that mir-21 overexpression is associated with induction of stemness through downregulation of tgf-betar2, a direct target of mir-21 and augmentation of -beta-catenin tcf/lef signaling pathway. 22855601_2 the identification of akt as a target of mir-378-3p led us to assess the potential influence of akt-inhibition on alternative activation by using a specific akt inhibitor, triciribine30 . 22855601_3 most likely this reflects the fact that mir-378-3p will target other, as yet-undefined target genes besides akt1 and thus have a much broader effect on the cellular phenotype, than discussed here. 25481410_1 overexpression of mir-206 decreased luciferase activity in hek 293a cells by 50% . 25481410_2 we did not observe any significant differences in luciferase activities following the overexpression of mir-28, mir-367, mir-493, mir-409, mir-185 and mir-34b 22723308_1 ews/fli1 regulates eya3 in ewing's sarcoma via modulation of microrna-708, resulting in increased cell survival and chemoresistance. 22723308_2 we further show that ews/fli1 mediates upregulation of eya3 via repression of mir-708, a mirna that target the eya3 3'-untranslated region, rather than by binding the eya3 promoter directly. 22723308_3 together, these data suggested that the major mechanism by which eya3 is overexpressed in ewing sarcoma is via ews/fli1 repression of mir-708, which target the eya3 3'-utr. 25197371_1 the molecular target of mir-137, cdc42 was down-regulated by ketamine in hippocampus. 20351093_1 notch1 and jagged1 are functional target of mir-34a. 20351093_2 besides, we have knockdown mir-34a in siha cells which has the highest endogenous mir-34a expression. 20351093_4 by using functional assays, mir-34a was demonstrated to bindto the 3'utrs of notch1 and jagged1. 20351093_5 western blot analysis using specific antibody against notch1 showed that the expression level of notch1 protein was decreased by 24 and 31% in the pre-mir-34a-transfected hela and jar cells, respectively . 21711453_1 the control, cotransfection of ets-1 3'-utr with a non-targeting sequence as well as of ets-1-mutated 3'-utr with mir-221/-222, did not show any repression in luciferase activity, confirming the specificity of such interactions . 21711453_2 ets-1 downregulation was confirmed at both mrna and protein levels in mir-222-transduced me1007 and me1402/r primary melanoma cell lines . in agreement with the luciferase results, overexpression of mir-221 did not show significant effects on ets-1 . 21711453_3 these results indicate that mir-222 is a true regulator of ets-1 expression. 21711453_4 surprisingly, the effect induced by cotransfection of mir-221 was negligible, suggesting that the coordinated function reported for mir-221/-222 in the regulation of p27kip, c-kit and other target genes can be uncoupled. 21711453_5 as expected, tm4-derived metastases displayed a significant increase of mir-222 and a correlated decrease of p27kip compared with controls . 22768238_1 next, we demonstrated that a snp , located within the microrna-7 binding site in the 3'-utr of hoxb5, could affect hoxb5 expression in bladder cancer mainly by differential binding activity of microrna-7 and snp-related mrna stability. 22768238_3 a mirna-binding snp located within 3'-utr of hoxb5 is associated with gene expression and may be a promising prognostic factor for bladder cancer. 22768238_4 these results indicated that mir-7 may regulate hoxb5 expression at both the post-transcription and mrna levels. 22768238_5 we found that the hoxb5 mrna and protein levels were down-regulated in the mir-7 transfected groups compared with the nc groups . 15618228_1 rydc binds hfq with high affinity and specificity, and the apparent binding constant of complex formation between the rna and the protein is compatible with its presence in vivo. 15618228_4 we conclude that rydc regulates the yejabef-encoded abc permease at the mrna level. 15618228_6 rydc doesn't directly ding to yejab mrna. 22078298_1 we also established that pak1 is a primary targetfor mirna222, and that increased levels of mirna222 following traumatic stress are accompanied by downregulation of pak1 expression. 22078298_2 as shown in figure figure2a2a and and2b,2b, the mirna222 mimetic decreased mrna levels for pak1; conversely, the mirna222 inhibitor increased the levels of pak1 mrna. 22078298_3 similar effects were observed at the protein level: expression of pak1 polypeptide was decreased by the mirna222 mimetic whereas the mirna222 inhibitor increased pak1 protein levels. 22078298_4 we conclude that pak1 is negatively regulated by mirna222. 22078298_5 figure 2 pak1 is a mirna222 target in summary, we report that c-src activation following traumatic stress leads to a robust increase in levels of mirna222 and a corresponding decrease in expression of the neuromodulator pak1, a confirmed targetfor mirna222. 18406353_1 mir-34 seed regions, and several individual genes, including cdk4, cdk6, cyclin e2 and e2f3 have been experimentally validated as mir-34 target by western blotting. 18406353_2 taken together, our data suggest that the effects of mir-34a on g1 cell cycle arrest are through the down-regulation of ccnd1 and cdk6, which is associated with other target of mir-34a either additively or synergistically. 20558617_1 here we demonstrate that mir-181a binds the 3' untranslated region of prox1, resulting in translational inhibition and transcript degradation. in this study, we demonstrate that the microrna mir-181a is in endothelial cells and binds to the prox1 3'-untranslated region , resulting in rapid and efficient transcript degradation and translational inhibition. 20558617_2 taken together, these data provide compelling evidence that mir-181a directly binds to and negatively regulates prox1 expression. 24875127_1 moreover, it was down-regulated in the cisplatin-resistant gastric cancer cell line sgc7901/cisplatin and the down-regulation of mir-1271 in sgc7901/dpp cells was accompanied by the up-regulation of insulin-like growth factor 1 receptor /insulin receptor substrate 1 pathway-related proteins, i.e., igf1r, irs1, serine/threonine-protein kinase mtor , and the apoptosis regulator bcl-2 , compared with the parental sgc7901 cells. 24875127_3 changes in the luciferase activity of reporter constructs harboring the 3'-untranslated region of the above proteins in sgc7901/ddp cells suggested that igf1r, irs1, mtor, and bcl2 were target genes of mir-1271. 26357588_1 promoter-reporter experiments supported the idea that mir-155, mir-186, mir-24, mir-27b, or mir-375 bind to the 3 ' utr of gabra4 and thereby inhibit protein production. 26357588_2 luciferase assay suggested that mir-155, mir-186, mir-24, mir-27b, and mir-375 can all bind to the 3 ' utr of gabra4. 25593579_1 transfection of mir-214 mimic showed protective effects on ogd-induced injury to h9c2 cells by reducing apoptosis, decreasing ldh and ck activities, rescuing the ogd-induced ca and down-regulating elevated protein levels of ncx1, bim, camkiiepsilon and cypd. 26213858_3 the results showed that sirt1 expression in the mir-204m-treated group was lower than the nc and mir-204i treated groups. 26257392_1 as confirmed by the luciferase activity assay, dnmt1 was a direct target of mir-152. 26257392_2 further study showed that mir-152 was involved in sal b treatment and targeted dnmt1, as confirmed by luciferase activity assays. 22123611_1 mir-195 promotes apoptosis of podocytes under high-glucose conditions via enhanced caspase cascades for bcl2 insufficiency. 24468065_1 mir-33a is up-regulated in chemoresistant osteosarcoma and promotes osteosarcoma cell resistance to cisplatin by down-regulating twist. 26473604_1 furthermore, 11 nutriregulated mirna were found to potentially target deg in which three predicted mirna chr3_3319-5p, chr9_13534-5p and chr12_18027-5p. of the 11 nutriregulated mirna that could target deg, let-7c-5p, mir-223-3p and mir-204-5pmay target seven, five and four deg, respectively . 26473604_2 notably, mir-204-5p and mir-223-3p are nutriregulated mirna with the highest fold change in high throughput sequencing. in addition, mir-223-3p may target five deg, three of which encode for zinc finger proteins that bind dna, suggesting that this mirna may indirectly regulate gene transcription. 26473604_3 consequently, the deregulation of mir-204-5p and mir-223-3p by food deprivation may have a significant impact in the mammary gland through the regulation of deg. 22761738_1 luciferase and western blot assays revealed that cyp2j2 was regulated by let-7b. 22761738_2 let-7b inhibits human cancer phenotype by targeting cytochrome p450 epoxygenase 2j2. 22761738_4 these results suggest that let-7b can inhibit the expression and tumor-promoting functions of cyp2j2. 22761738_5 these results indicated that the enhancing effect of cyp2j2 on tumor formation could be attenuated by let-7b. 22761738_6 these data showed that human cyp2j2 is directly downregulated by let-7b. 22761738_7 these data indicate that cyp2j2 is one of the target of let-7b. 26073885_1 identification of tnf-alpha and il-12p40 as targets of mir-17. 25675046_1 therefore, this assay confirmed that e2f3 was a direct downstream target of mir-34a. 19850724_1 in the current study, we have validated that the rhob mrna is a bona fide mir-223 target in order to validate rhob as a true mir-223 target we used reporter assays to validate the mir-223/rhob 3'-utr interactions at the two targetsites. 19850724_4 these data provide further validation that rhob is a mir-223 target 26501435_1 mir-30d directly targeted snail in ovarian cancer cells. 26501435_2 these data verified that mir-30d directly bound to the 3' utr of snail to suppress its expression and consequently inhibited the emt process. 26116538_1 in our study, we identified pak5 as the direct targets of mir-129 as well. 26116538_2 to confirm the direct binding between mir-129 and pak5 3 ' utr, we constructed 3'utr sequence of pak5 and inserted into luciferase reporter vector. 26116538_3 taken together, our findings indicated that mir-129 played a critical role in regulating pak5 expression. 19665978_1 to prove functional relevance of bmi1 regulation by mir-200c, we constructed a bmi1 expressing lentivirus in which bmi1 cdna does not contain the 3'-utr sequence that is targeted by mir-200c. 19665978_2 co-expression of this bmi1 transgene substantially rescued the defect in colony formation of breast cancer cells infected with the mir-200c lentivirus . 19665978_3 these results suggest that bmi1 is one of the key functional target of mir-200c, at least with respect to the ability of mir-200c to suppress colony formation of breast cancer cells in vitro. 24854555_3 mir-192 binded to bim 3'-utr and negatively regulated bim expression at the post-transcriptional level in lung adenocarcinoma cells. 21750649_1 as a result, overexpression of mir-7 significantly reduced the expression of bcl-2 at mrna level . 21750649_3 compared with control groups, bcl-2 expression was remarkably reduced in response to mir-7 transfection for 48h . 21750649_4 taken together, these results suggested that mir-7 could decrease expression of bcl-2 through direct 3'utr interactions. 21750649_5 these results indicate that mir-7 may suppress bcl-2 expression by targeting the 3'-utr of bcl-2 mrna. in summary, this study further extends the biological role of mir-7 in nsclc a549 cells and for the first time identifies bcl-2 as a novel targetpossibly involved in mir-7-mediated growth suppression and apoptosis induction of a549 cells. 19900756_4 further comparisons of formalin-fixed paraffin-embedded human choriocarcinoma, mole, and non-cancer trophoblast tissues confirmed the initial findings of low mir-199b expression and set upregulation in choriocarcinomas, suggesting that microrna-dysregulated set protein may account for the rapid growth seen with choriocarcinomas. 25413124_1 thus, our results suggest that mir-155 might be involved in the pathogenesis of itp by regulating cytokine profiles, which may be mediated by mir-155 targeting socs1. 25251394_2 these findings indicate that hypoxia-responsive microrna-377 directly targets vegf in mscs, and knockdown of endogenous microrna-377 promotes msc-induced angiogenesis in the infarcted myocardium. 25251394_3 furthermore, both dual-luciferase reporter assay and western-blotting verified that mir-377 can directly bind with vegf 3'-utr leading to negatively regulation of its expression. 20233879_1 to confirm the binding of mir-519c to the 3'-utr region of hif-1alpha, we generated a mutant form of mir-519c harboring corresponding mutations to the mutant hif-1alpha 3'-utr. in contrast, hif-1alpha mrna levels were unchanged in all cell lines , indicating that mir-519c regulates hif-1alpha in a posttranscriptional manner. 20233879_2 all these effects could be reversed by coexpressing a dominant-negative hif-1alpha construct, emphasizing the regulatory role of mir-519c in hif-1alpha-dependent angiogenic induction. 20233879_3 to test the involvement of mir-519c in hif-1alpha-dependent angiogenesis in vivo, mice were s.c. 20233879_5 we concluded that mir-519c downregulates angiogenesis both in vitro and in vivo through the inhibition of hif-1alpha. 23870455_1 mir-26a directly targeted prohibitin whose expression levels were downregulated in glioma specimens. 23870455_2 these results reveal that mir-26a regulates phb and promotes glioma progression both in vitro and in vivo and that mir-26a and its target phb are associated with glioma development, which can be helpful in developing microrna-based treatment for glioma in the future. 23870455_3 we validated phb as a novel target gene of mir-26a and found the inverse correlation between mir-26a and phb in glioma specimens. 23870455_4 this result suggested that mir-26a regulates phb transcriptional activity by binding the seed sequence at its 3'-utr. 23870455_5 these results indicated that mir-26a directly targets phb by binding to its seed sequence at 3'-utr. 25824045_1 findings of this study demonstrated that total mir-107 or mir-25 expression might be overexpressed in gastric cancer patients and they can simultaneously and synchronically regulate lats2 expression, thereby affecting gastric cancer cell growth and invasion. 25824045_2 in the current study, we explored the expression pattern of these two mirnas in gac patients and firstly reported that mir-107 and mir-25 can simultaneously targeting large tumor suppressor 2 and synchronically modulate its expression, thereby promoting proliferation and invasion of gac cells. 25824045_3 these results suggest that both mir-107 and mir-25 can directly target lats2 and modulate its expression. 26735582_1 moreover, for sgc-7901 cells, mir- 711 was found to downregulate cdk4 expression, and to arrest the cell cycle in the g1 phase. 26735582_2 these results suggested that mir-711 could downregulate cdk4 expression to inhibit the viability of sgc-7901 cells. in summary, this study showed that rassf1a could suppress the viability of sgc-7901 cells by mir-711-mediated downregulation of cdk4 expression. 17940140_1 wt1-as transcripts are exported into the cytoplasm and form heteroduplexes with wt1 mrna in the overlapping region in wt1 exon 1.these results show that wt1 encodes conserved antisense rnas that may have an important regulatory role in wt1 expression via rna:rna interactions, and which can become deregulated by a variety of mechanisms in cancer. 26875838_1 overexpression of mir-130b or mir-181d was able to significantly reduce the luciferase activity of 211 hela cells transfected with the pig gr 3'-utr reporter plasmid, as compared with the 212 scramble control . 26577528_1 thus confirming that mir-34a, mir-34b, and mir-34c interact directly with the pdl1 3'utr 23856992_2 the ectopic expression of mir-503 reduced the bcl-2 protein level and sensitized the a549/cddp cells to cisplatin-induced apoptosis. 25531908_1 further investigation revealed that mir-124 bound directly to the 3' utr region of stat3, thereby inhibiting stat3 expression. in addition, mir-124 levels detected in nsclc tissues were lower than those in adjacent normal lung tissues, while the opposite was observed for stat3. in nsclc, the expression levels of mir-124 and stat3 correlated significantly with the tumor node metastases stage, differentiation grade and lymph node metastasis, while the levels of these molecules did not differ significantly by gender, age, location, smoking index, pleural invasion or pathological type. 25531908_2 to further prove that stat3 is a target of mir-124, we evaluated the expression levels of stat3 in the three cell lines 48 h after transfection using real-time pcr and western blotting. 25531908_3 the results from these assays show that stat3 was significantly downregulated in a549-mir-124 cells compared to a549-mir-nc or untransfected cells . 21852381_1 3'utr of zeb2 and bmi1 are functional target of mir-708 in renal cancer. 21852381_2 we investigated whether the 3'-utr of zeb2 and bmi1 are functional target of mir-708 in renal cancer. 21852381_3 transient transfection of human a498 cancer cells with the respective 3'-utr plasmids along with different concentrations of mir-708 precursor led to a significant decrease in promoter activity when compared with the control vector suggesting that mir-708 directly represses these genes. 26371058_1 additionally, cox-2 is a direct target of mir-101b and mir-26b in the macrophages. 26371058_2 significant upregulation of mir-101b and mir-26b effectively prevented lps-induced excessive expression of cox-2 in the young mice. 26371058_3 tsa-induced increased expression of mir-101b and mir-26b could further suppress cox-2 expression. 26371058_4 mir-101b and mir-26b target cox-2 and repress the translation of cox-2 mrna in mouse macrophage. 26371058_6 5e, f, transfection of mir-101b or mir-26b mimics caused a decrease in cox-2 protein expression, but not its mrna levels, while transfection of mir-101b or mir-26b inhibitors notably elevated cox-2 protein expression, but not mrna levels, indicating that both mir-101b and mir-26b negatively regulated cox-2 expression by suppressing the translation of cox-2 rather than mrna stability. 24667580_1 upregulation of mir-497 in bxpc-3 and aspc-1 pancreatic cancer cell lines inhibited proliferation, enhanced apoptosis, re-sensitized cells to gemcitabine and suppressed igf-1r and p-akt expression through direct downregulation of igf-1r protein expression. 26324048_1 figure 3. western blot revealed that the expression level of foxo3 in cells transfected with mir-155 mimics decreased. 26324048_2 alignment between the predicted mir-155 target site of the foxo3 3'-utr region and mir-155 21804529_8 moreover, these experiments indicate that the regulation of cav1.2-ltc by mir-103 is bidirectional since knocking-down or over-expressing mir-103, respectively, up- or down- regulate the level of cav1.2-ltc 26159460_1 taken together, the data suggested that mir-378 could target e2f2 and ranbp10 mrna directly by binding the mre within the 3'-utr. 26159460_2 to further investigate the mechanism by which mir-378 targets and regulates e2f2 and ranbp10, the effect of mir-378 overexpression on the mrna and protein expression levels of endogenous e2f2 and ranbp10 was examined. 1372677_1 the 53-nucleotide rna molecule encoded by gene dicf blocks cell division in escherichia coli by inhibiting the translation of ftsz mrna. 1372677_2 such a role for dicf had been predicted on the basis of the complementarity of dicf rna with the ribosome-binding region of the ftsz mrna. 26209011_1 interestingly, the putative mir-192-5p target binding sequences at the 3'-utr of human scn5a are not evolutionarily conserved. 26209011_2 the data suggests that mir-192-5p negatively regulates the activity of pmir-scn5a-3- utr luciferase reporters by targeting the mir-192-5p target binding sequence . 19574223_5 silencing of the microrna processing enzymes, drosha and dicer, led to an increase in foxo1 expression. 19574223_6 we also identified functional and specific microrna target sites in the foxo1 3'-untranslated region for mir-27a, mir-96, and mir-182, micrornas that have previously been linked to oncogenic transformation. 19574223_7 the three micrornas, mir-27a, mir-96 and mir-182, were observed to be highly expressed in mcf-7 breast cancer cells, in which the level of foxo1 protein is very low. 19574223_8 antisense inhibitors to each of these micrornas led to a significant increase in endogenous foxo1 expression and to a decrease in cell number in a manner that was blocked by foxo1 sirna. 19574223_10 we have identified a novel mechanism of foxo1 regulation, and targeting of foxo1 by micrornas may contribute to transformation or maintenance of an oncogenic state in breast cancer cells. 24609901_1 however, possibly as a compensatory effect, mir-22 was also upregulatedduring the chemotherapy, and the overexpressed mir-22 targeted the 3' utr of hmgb1 and inhibits the hmgb1-promoted autophagy. 22240480_1 the interaction between mir-28-5p and hoxb3 occurs through a direct binding as demonstrated by the luciferase assay results. 25622783_1 furthermore, notch3 and mapk3, the members of notch signaling and erk-mapk pathway, were demonstrated to be regulated by mir-483-5p based on negative expression correlation validation and detection of notch3/mapk3 expression after mir-483-5p mimics transfection. 25622783_2 dual luciferase activity assay suggested that notch3 and mapk3 were directly targeted by mir-483-5p. 26917013_1 taken together the mitrap studies revealed that the long igf2bp1 transcripts are subjected to regulation by multiple mirnas with the let-7 family presenting the most potent class of regulators. 26917013_2 the igf2bp1 mrna is a key target of the let-7 mirna family. 22366319_3 thus, the mir-125b targetlin28a is an important regulator of hematopoiesis and a primary target of mir-125b in the hematopoietic system. 22366319_4 searching for a mechanism by which mir-125b exerts its effects on the hematopoietic system, we found that the direct target of mir-125b, lin28a, is also a regulator of hematopoiesis. the mir-125b seed sequence within 3- utr of lin28a has been previously identified and shown to be functionally important for mir-125b repression . in our study, manipulating lin28a expression levels in mice mimicked the hematopoietic phenotypes of those mice with modulated mir-125b levels. 22850539_1 in silico target prediction analysis revealed complementarity of mir-29c to the 3'-untranslated region of bcl2l2 mrna. 22850539_2 targeting of bcl2l2 3' utr by mir-29c was determined by luciferase assay. 21354697_1 we further demonstrated that the tumor suppressive role of mir-203 was mediated by negatively regulating akt2 protein expression through mrna degradation. 21354697_2 there are no obvious changes being observed in p53, pten, and phospho-pten levels in mir-203-transfected cells, suggesting that the decreases in akt2 mrna and protein levels may be caused by targetedegradation of mir-203 mrna. 21354697_3 3. the targeting sites of mir-203 at the 3' utr of akt2 gene. 21354697_5 transfection of mir-203 decreased akt2 mrna level in ht-29 and hct-15 cells, but slightly increased akt2 mrna level in hct-116 cell. 21354697_7 overexpression of mir-203 downregulated akt2 protein levels in ht-29 and hct- 15 cells, but akt2 was slightly upregulated in hct-116 cell. 21354697_8 the chemosensitive role of mir-203 was mediated by targetinhibition of akt expression at post-transcriptional level, subsequent inhibition of mtdh and hsp90 expression, and decrease of anti-apoptosis gene bcl-xl and increase of apoptotic protein bax and active caspase-3 levels. 26175849_1 as shown in figure 3b, mir-29b overexpression inhibited the transcriptional activity of a luciferase reporter containing the stat3 3'-utr. 26175849_2 collectively, these results indicated that the expression of mir-29b could suppress the expression of her-2 through targeting its upstream gene stat3 signaling in breast cancer cells. 24974767_1 network analysis were further conducted on mrna-mirna pairs, which revealed that mir-219-5p-mt1f and -trib3 pairs by agnps are being involved in various cellular processes, such as, oxidative stress, cell cycle and apoptosis. 23142219_1 we further showed pyk2 is a target of mir-517a and mir-517c and both the mirnas are downregulated in hcc samples. 23142219_2 results showed overexpression of mir-517a and mir-517c induced a significantly decreased pyk2 expression in yy8103, mhcc97-h and hepg2 cells . 23142219_3 these data indicate pyk2 was a target of mir-517a and mir-517c. 23142219_4 these results collectively suggest that mir-517a and mir-517c regulate the expression of pyk2 via mrna degradation. 23142219_5 the luciferase assays, together with the changes in transcriptional level of pyk2 indicate that mir-517a and mir-517c directly regulate pyk2 expression through specific binding to the 3' utr and cleaving its mrna. 26460801_5 for example, hsa-mirna-454 showed 46.4% inhibition of irf1 and 46.9% of traf6, and hsa-mirna-671 showed 49.7% inhibition of il1-r1 and 56.8% inhibition of fiir. 26460801_7 we observed that transfection by hsa-mirna-454 and hsa-mirna-328 significantly reduced tsc1 and 4ebp1 expression . in addition, hsa-mirna-671 significantly downregulated il1r1 expression , and hsa-mirna-146b downregulated irak1 . 26617798_1 in addition, bone morphogenetic protein-7 was identified as a target of mir-137 in nsclc cells, luciferase reporter assay suggested that mir-137 directly targeted 3'-utr of bmp7, and correlation analysis revealed that bmp7 inversely correlated with mir-137 in nsclc tissues. 26617798_3 taken together, these data suggested that bmp7 was a target of mir-137 in nsclc cells. 26617798_4 we further identified bmp7 as a direct target of mir-137 in nsclc cells. 26560875_1 taken together, our data show that mir-20a directly targets the fpn-3'-utr and negatively regulate fpn mrna levels. 20090763_1 to test whether mir-34 family exerts an effect downstream of p63 to regulate the expression of cell cycle proteins, we measured the protein levels of a subset of cell cycle regulators in the presence or absence of p63 and mir-34 family. 20090763_3 concomitant downregulation of both mir-34a and mir-34c resulted in a significant rescue of the expression of cyclin d1 and cdk4, the two known mir-34 target, whereas cdk2 remained unaffected . 20813867_1 a targetsequence for mir-192 and mir-215 is present in the 3'untranslated region of wnk1. 20813867_2 mir-192 and mir-215 functionally interact with their targetsequence within wnk1 3'-utr in vitro. 20813867_3 taken together, these data suggest that mir-192 and mir-215 could regulate wnk1 expression in a dose-dependent manner through binding to their targetsequence in the 3'-utr of the gene. 18504431_1 we demonstrate that microrna-146a and microrna-146b when expressed in the highly metastatic human breast cancer cell line mda-mb-231 function to negatively regulate nf-kappab activity. 18504431_3 these findings implicate mir-146a/b as a negative regulator of constitutive nf-kappab activity in a breast cancer setting and suggest that modulating mir-146a/b levels has therapeutic potential to suppress breast cancer metastases. 21233845_1 we demonstrate that mir-885-5p downregulates cyclin-dependent kinase and mini-chromosome maintenance protein , activates p53, and provide evidence that cdk2 and mcm5 are direct mir-885-5p target. 21233845_2 accordingly, our data from in silico prediction and western blotting support that cdk2 and mcm5 are targeted by mir-885-5p. 21233845_3 these data show that mir-885-5p directly target predicted mir-885-5p binding sites in the cdk2 and mcm5 3'-utrs. 21233845_4 although both cdk2 and/or mcm5 knockdown and mir-885-5p transfection in sk-n-be c upregulated p53, they did not undergo apoptosis, suggesting that target other than cdk2 and mcm5 modify the sk-n-be c response to mir-885-5p. 21186079_1 using a luciferase-reporter assay, we show that mir-185 expression significantly suppressed the rhoa and cdc42 3'utr activities, and the inhibitory effect was lost when the putative targetsites for mir-185 were mutated. 21186079_2 these results indicate that mir-185 can directly impact rhoa or cdc42 expression through the predicted sequence sites. 21186079_3 we conclude that rhoa and cdc42 are mir-185 target that are subject to negative regulation by mir-185. 21186079_5 these data suggest that mir-185 negatively regulates invasion of the colorectal cancer cells, and this effect is at least in part due to its rhoa and cdc42 targeting activity. 26646296_1 bioinformatics analyses showed that mir-138 targeted the 3'-utr of zeb2 mrna to inhibit its translation, which was confirmed in a luciferase-reporter assay. 26646296_2 the luciferase activities were quantified in these cells, suggesting that mir-138 specifically targets 3'-utr of zeb2 mrna to inhibit its translation . 26646296_3 together, these data suggest that mir-138 inhibits zeb2 protein translation in t24 cells. 26646296_4 using promoter luciferase assay, we foun that mir-138 inhibited zeb2 through translation suppression. 26738853_1 using a mir-146a target pcr array, we screened 88 genes including experimentally verified and bioinformatically predicted target genes in opcs transfected with mir-146a mimic and control mirnas. 26738853_2 compared to the control mirnas, mir-146a mimics substantially reduced the transcripts of irak1, irak2, traf6, and numb , which are well-validated genes targeted by mir-146a . in addition, mir-146a downregulated target genes such as a disintegrin and metalloproteinase with thrombospondin motifs 3 , breast cancer 1, 2 , fas-associated via death domain , notch 2, and sortilin 1 , which are known to regulate biological function of opcs . in parallel, mir-146a also decreased traf6 protein levels, another gene targeted by mir-146a . 26738853_3 reduction of irak1 and traf6 by mir-146a was associated with a decrease of nf-kappab p65 proteins , that are known to be regulated by irak1 . 26738853_4 these data suggest that mir-146a targets irak1. 23325762_1 here, we report that mir-7 modulates the e/a switch by acting directly on ttk69 transcripts. 23325762_2 here, we report that the microrna mir-7 exerts an additional layer of regulation in this developmental switch by regulating ttk69 transcripts. 23325762_3 in stage 10b cells overexpressing mir-7, ttk69 expression was lower than in wild-type neighboring cells , suggesting mir-7 can regulate ttk69 expression levels during the e/a switch. 23325762_4 these results indicate that mir-7 regulates ttk69 levels in a dose-dependent manner in follicle cells during the e/a switch. in the follicle cells, the change in expression of ttk69 in response to mir-7 levels is striking, even the heterozygous mir-7 mutant follicle cells showed upregulated ttk69 expression, suggesting a dose-dependent regulation by mir-7. 26088362_2 collectively, our results demonstrate that the 3'-utr of epha2 mrna is directly targeted by mir-200a. 26471298_1 expression of klf4 is negatively regulated by mir-32. 26471298_2 these results indicated that klf4 was a target gene of mir-32, and the position of 674e681 in the 3'-utr of klf4 is the mir-32 binding site. 26471298_3 mir-32 suppresses klf4 expression by directly targeting the klf4 3- untranslated regions . 23562878_1 ectopic let-7c expression increased the in vitro and in vivo chemo- or radiosensitivity of dtx-resistant lad cells through enhanced apoptosis,further investigation suggested that let-7c significantly reduced the luciferase activity of a bcl-xl 3'-utr-based reporter, concordant with reduced bcl-xl protein levels. 26673620_2 ksr1 was one of the putative targets of mir-497. 26673620_3 forced expression of mir-497 attenuated ksr1 protein expression and erk activation, a known downstream molecule , suggesting that mir-497 directly targets ksr1 by binding its seed region of the 3'-utr region in human crc cells. 26673620_4 as we expected, forced expression of ksr1 also restored mir-497-inhibited cell proliferation, migration and invasion , suggesting that mir-497 suppresses human crc cell proliferation, migration and invasion by inhibiting its target ksr1. 20668090_1 we show that mir200b and mir429, but not mir200a, can induce ebv-positive cells into lytic replication by downregulating expression of zeb1 and zeb2, leading to production of infectious virus. 26878281_1 luciferase assay and protein expression results confirmed the direct binding effect between ctnnb1 and mir-200a following pq exposure. 26878281_2 finally, these data indicated that mir-200a interacts with specific elements in the 3 -utr of ctnnb1. in this present study, we identified ctnnb1 as the functional downstream target of mir-200a by using both bioinformatic and experimental analyses. 26191186_1 in addition, in crl-7566 cells, knockdown of endogenous mir-191 by antagomir-191 abrogated its inhibition on luciferase activity of luc-dapk1-wt. 26191186_2 in crl-7566 cells, transfection of mir-191 mimics, similar as sidapk1, could significantly reduce dapk1 expression . in crl-11731 cells, transfection of antagomir-191, similar as infection with dapk1-mut lentiviral particles, could significantly increase dapk1 expression . 26191186_3 these results suggest that mir-191 can directly target dapk1 mrna and regulate its expression. 26191186_4 these results suggest that mir-191 modulates responses of ovarian endometriosis and endometrioid carcinoma cells to tnf-alpha by targeting dapk1. 20534588_2 we found that inhibition of mir-214 expression with 214in increased whereas enhancing mir-214 expression with 214mi decreased n-ras mrna levels relative to that in the control cells transfected with a nonspecific mirna. 25476932_2 collectively, these results suggest that mir-205 inhibits hr-mediated dna damage repair and radioresistance by targeting zeb1 and ubc13. 10954740_2 a computational reexamination of the hns coding sequence revealed a second potential interaction of hns with dsra. 10954740_4 base pairing between dsra and the two regions of hns would form a contiguous coaxial stack, looping out the middle part of hns mrna. 19250063_2 we showed that mir-16, in mcf-7 and hela cell lines, down-regulates the expression of caprin-1, hmga1a, hmga1b and cyclin e at the protein l 21216304_1 when only plexin-b1-3'utr or plexin-b1-3utrmut was transfected into hela cells, the fiuorescence intensity of plexin-b1-3'utr was significantly decreased because of the function of endogenous mir-214. 21216304_2 these data suggest that mir-214 could be involved in the regulation of plexin-b1 in cervical cancer. 21216304_3 as a result, when mir-214 was over-expressed in hela/mir-214, the expression of plexin-b1 mrna and protein was significantly decreased compared to that in hela/neg-ctrl . 21216304_4 the specific interaction between mir-214 and plexin-b1 3'utr to inhibit egfp fluorescence is evident in fig. 21216304_6 this observation demonstrated that mir-214 directly and specifically interacted with plexin-b1 mrna and promoted plexin-b1 protein silencing mostly through a post-transcriptional repression mechanism. 21216304_7 these data showed that elevated expressions of mir-214 can cause effects similar to the plexin-b1 knockdown by sirna on hela cells, which further supported that mir-214 affected cell functions via downregulation of plexin-b1. 26822621_1 we confirmed that mir-193b-3p could repress tgf--beta2 expression by directly binding to a conserved 3'-utr site of tgf--beta2. 26822621_2 these findings indicated that mir-193b-3p could suppress htr8/svneo trophoblast cell migration and invasion through regulating tgf--beta2. 26636522_1 mir-150 could directly target 3'-utr of p27 and decrease its expression, through which it increased the number and volume of tumor sphere formed by du145 cells, as well as the expression of csc related oct4, nestin and nanog genes. in this study, by using dual luciferase assay and western blot analysis, we verified that mir-150 can directly target p27 and suppress its expression. 14580258_1 another interpretation based on previous results would be that ahif could specifically destabilise hif-1alpha mrna but not shif-1alpha transcript, resulting in larger amounts of the spliced form for elevated amounts of ahif. the death risk for patients with elevated ahif transcript concentration was 2.8-fold that in patients with a low concentration of hif-1alpha antisense. 26885269_1 bioinformatics analyses predicted that mir-506 may target the 3'-utr of snail2 mrna to inhibit its translation, which was confirmed by luciferase-reporter assay. 26885269_2 the luciferase activities were quantified in these cells, suggesting that mir-506 targets 3'-utr of snail2 mrna to inhibit its translation . 26885269_3 these data suggest that mir-506 inhibits snail2 protein translation in u2os cells. 25652855_2 mir-204 could inhibit hcc cell proliferation and induce apoptosis by down-regulating the expressions of bcl-2 and sirt1. 26629059_2 these results demonstrate that mir-429 targets the predicted site within the 3'-utrs of xiap mrna in the tnbc cell line. 26629059_3 moreover, we showed using a luciferase assay that the 3'-utr of xiap has a functional target of mir-429. 26662310_1 here, in our present study, to investigate the mechanism of mir-615-5p, bioinformatic prediction and luciferase reporter assay were employed to ascertain the downstream target of mir-615-5p finding that the serine hydromethyltransferase 2 was the direct downstream target. 26662310_2 besides, knockdown or overexpression of shmt2 can suppress or promote both proliferation and migration of hcc cells, indicating that mir-615-5p can directly and negatively regulate the shmt2 in hcc cells. 26662310_3 it can be seen that mir-615-5p was able to directly and negatively regulate shmt2 expression in hcc cells, indicating that shmt2 was a direct and negative downstream target of mir-615-5p. 26662310_4 furthermore, in in vitro hcc cell lines, we for the first time found that shmt2 was a novel downstream target that was able to be directly and negatively regulated by mir-615-5p, which was distinctively different from previous reports. 22810507_1 profiling microrna expression delineated tp53 alteration-associated mirna profiles, and identified mir-34a and mir-100 as the most significantly down- and upregulated mirna, respectively. 26579707_1 these findings demonstrated that mir-130b directly interacted with the predicted target site of the pgc-1alpha mrna and negatively regulated its expression 21163928_1 this effect was dependent on the seed region in the ptpn9 mrna 3'-utr, as mutation or deletion of this site relieved the repressive effect of mir-126 . 21163928_3 these results suggest that, although ptpn9 is a target of mir-126, it alone is not sufficient to rescue the effects that mirs-126/126* have on erythropoiesis. 26075299_1 meanwhile, the luciferase assay showed that met was a direct target of mir-206. 26075299_2 the results in fig. 4 suggest that mir-206 down-regulated the expression of met by targeting its 3 ' utr. 26075299_3 analysis results showed that mir-450b-5p targeted zeb2, mir-335-5p targeted plau, mir-34a-5p targeted ajap1, mir-206 targeted met, mir-302b-3p targeted ptprg and mir-424-3p targeted thbs2. 26075299_4 luciferase report assay results proved that met was a direct target of mir-206 in lung cancer 95d and 95c cells. 23613494_1 meanwhile, lentiviral overexpression of mir-424 inhibited neuronal apoptosis and microglia activation, including suppressing ionized calcium binding adaptor molecule-1 immunoreactivity and protein level, and reduced tumor necrosis factor-alpha production. in vitro study demonstrated that mir-424 mimics caused g1 phase cell-cycle arrest, inhibited bv2 microglia activity, and reduced the mrna and protein levels of cdc25a, cyclin d1, and cdk6 in bv2 microglial cells, which were upregulated in brain of middle cerebral artery occlusion mice. 10208747_1 sup-39 suppresses mel-11 and enhances let-502 24841638_1 further mechanistic analysis suggested that mir-451 overexpression accelerated cell death in a caspase-3-dependent manner, as pretreatment with its inhibitor z-vad-fmk notably attenuated mir-451-induced cell apoptotic rates. 24841638_2 moreover, mir-451 upregulation abrogated cell invasive ability, accompanied with the decrease of matrix metalloproteinase-9 expression levels, which may contribute to mir-451-triggered cell apoptosis. 26358730_1 similarly, up-regulation of esr1 and zbtb4 by knocking down mir-18a suggested esr1 and zbtb4 were functional target genes of mir-18a 20080955_1 site-directed mutagenesis of kshv mirna predicted target sites in the maf 3'utr abolished silencing, confirming that mir-k12-1, mir-k12-6-5p, and mir-k12-11 regulate maf by interacting with the 3'utr. 21203424_1 moreover, we demonstrated that mir-96 downregulated foxo3a expression by directly targeting the foxo3a 3'-untranslated region. 21203424_2 moreover, point mutations in the tentative mir-96-binding seed region in foxo3a 3'-utr abrogated the suppressive effect of foxo3a mediated by mir-96 . 21203424_3 taken together, our results demonstrate that foxo3a is a bona fide target of mir-96. 21203424_4 as shown by the luciferase reporter assay, inhibition of mir-96 decreased transactivities of foxo3a in a dose-dependent manner in both breast cancer cell lines , indicating that inhibition of mir-96 results in upregulation and increased transactivity of foxo3a. 21203424_5 taken together, our results suggest that suppression of foxo3a plays an important role in promotion of cellular proliferation by mir-96. 26175229_1 these results indicated that overexpression of mir-206, either by transfection with an mir-206 mimic or naturally in cad patients, down-regulates pik3c2alpha expression. 22509021_1 we also identified and validated mir-155 binding sites in the 3' utrs of the target, tspan14, lpin1, and pmaip1. 22509021_2 using microarray analysis, we confirmed the mir-155-dependent down-regulation of known mir-155 gene target during infection and validated mir-155 binding sites in the 3- utrs of putative mir-155 target tspan14, lpin1, and pmaip1. 22056881_1 interestingly, the abundance of mir-375 was inversely correlated with that of aeg-1 , a potential target of mir-375. 22056881_2 interestingly, aeg-1 is a putative target of mir-375 . 22056881_3 luciferase assay indicated that mir-375 could directly aim at its predicted binding site of aeg-1 and lead to the suppression of luciferase expression of pluc-aeg-1, whereas mir-375 had no obvious effects on its control pluc-mutaeg-1 . 22056881_4 overexpression of mir-375 in hepg2 cells greatly reduced the mrna and protein level of aeg-1 , whereas inhibition of mir-375 in normal phhc cells enhanced aeg-1 mrna and protein expression . 22056881_5 moreover, mir-375 was significantly downregulated whereas aeg-1 was upregulated in hcc tissues, and a significant inverse correlation was found between mir-375 and aeg-1 expression . 22056881_6 these results suggested that mir-375 suppressed aeg-1 expression by binding directly to the 3'-utr of aeg-1, and the negative regulation of aeg-1 by mir-375 might contribute partially to antitumor effects of mir-375 involved in hcc. 23266610_1 hbxip is a mir-501 target dual luciferase reporter assays demonstrated that expression of the hbxip 3'-utr reduced luciferase activity . 23266610_2 qrt-pcr and western blot analysis demonstrated that hbxip mrna and protein expression were markedly up-regulated in hepg2.2.15 cells that had been transfected with anti-mir-501 . 23266610_3 these data demonstrated that mir-501 significantly down-regulated hbxip expression by binding to the 3' utr of hbxip mrna. 23266610_4 however, there was no significant difference between the sirna-transfected and the anti-mirna control transfected cells , indicating that down-regulating hbxip rescued the inhibition of hbv replication that was induced by mir-501 knockdown. 22926857_2 targetscan,18 pictar,23 and microt24 found 3 putative targets of mirna-206 in the 3'-utrs of the mice and human genes encoding bdnf ..to determine which mirnas are responsible for the regulation of bdnf in ad mice, we used a microarray to compare mirna levels between 7- and 12-month old wt and tg2576 mice,only mir-206 and mir-182 were upregulated . 22926857_4 this real time pcr analysis showed that only mir-206 is upregulated in 12-monthold tg2576 mice . in situ hybridization also revealed enhanced and diffuse expression of mir-206 in the brains of 12-month-old tg2576 mice. 19380620_8 furthermore, transgenic mice with cardiac-specific overexpression of mir-320 revealed an increased extent of apoptosis and infarction size in the hearts on i/r in vivo and ex vivo relative to the wild-type controls. 19380620_9 conversely, in vivo treatment with antagomir-320 reduced infarction size relative to the administration of mutant antagomir-320 and saline controls. 19380620_11 this was validated experimentally by utilizing a luciferase/gfp reporter activity assay and examining the expression of hsp20 on mir-320 overexpression and knockdown in cardiomyocytes. 19380620_12 our data demonstrate that mir-320 is involved in the regulation of i/r-induced cardiac injury and dysfunction via antithetical regulation of hsp20. 23255074_1 mir-218 inhibited the expression of bmi-1 via binding to its 3'-utr. 23255074_2 cotransfection experiments showed that mir-218 decreased the luciferase activity of luc-bmi-1 3'-utr for 34%, but this was not observed on luc-bmi-1-mut 3'-utr , indicating that bmi-1 is a direct target of mir-218 through binding to 3'-utr of bmi-1. 23255074_3 this result was concomitant with luciferase reporter activity results, inferring that mir-218 directly interacts with bmi-1 3'-utr to repress its translation. 23255074_4 expression of bmi-1 and mir-218 exhibited a significant inverse correlation calculated by pearson correlation , further supporting the mir-218 targetstatus of bmi-1. 23255074_5 we thus supposed that mir-218, a direct target of bmi-1, might repress crc growth through bmi-1 downregulation. 26573388_1 these results demonstrated that mir-143 directly targeted dnmt3a by binding their 3'-utrs, thus suppressing protein expression. 24262949_3 we demonstrated that mir155 targets multiple players in mtor signaling, including rheb, rictor, and rps6kb2. 24262949_4 mir155 suppresses target-gene expression by directly interacting with their 3' untranslated regions , mutations of the binding sites abolish their mir155 responsiveness. 10924331_1 the mnsod mrna 3' utr contains a 280-bp region that shows high homology to human alu and 7sl sequences. 10924331_2 mnsod 3' utr probes hybridize to a specific cytoplasmic rna species of approximately 300 nucleotides. 10924331_3 this antisense rna is most likely 7sl rna based on its size, ubiquitousness, high levels, and lack of inducibility. 10924331_4 taken together, these results suggest that naturally occurring antisense rna may bind mnsod mrna and repress its expression. 26255969_1 nuak1 was found to be a direct target of mir-145 regulation. 26255969_2 the overexpression of mir-145 in icc cell lines inhibited proliferation, growth, and invasion by suppressing nuak1 expression, which was associated with a decrease in akt signaling and matrix metalloproteinase protein expression. 26762267_2 confirming that twist is a direct target of mir-548c, and binding of mir-548c to the 3'-utr of twist mrna is sufficient to reduce twist protein levels. 19006648_3 furthermore, resected normal/tumor tissues of 25 hcc patients demonstrated an inverse correlation between mir-34a and c-met-protein. in hepg2 cells, ectopic expression of mir-34a potently inhibited tumor cell migration and invasion in a c-met-dependent manner. 19006648_4 mir-34a directly targeted c-met and reduced both mrna and protein levels of c-met; thus, decreased c-met-induced phosphorylation of extracellular signal-regulated kinases 1 and 2 . 26072217_1 these results indicate that mir-365 may promote the expression of cdk6 and cdk4 by targeting nfib. 26072217_2 these results indicate that mir-365 targeting of nfib leads to the repression of cdk6 and cdk4. 26072217_3 cdk6 and cdk4 are regulated by mir-365 through nfib. 18716031_5 mirna23b interacts with the mor1 3'-utr via a k box motif. 18716031_6 by knocking down endogenous mirna23b in ns20y cells, we confirmed that mirna23b inhibits mor1 protein expression in vivo. 18716031_8 we propose a mechanism in which mirna23b blocks the association of mor1 mrna with polysomes, thereby arresting its translation and suppressing the production of mor1 protein. 26914935_1 to investigate whether mir-99a/mtor signaling pathway is involved in cardiomyocytes hypertrophy, we assessed the expression of mir-99a and its target mtor in hypertrophic nmvms. 26914935_2 taken together, these results demonstrated that both mtor and mir-99a expressions were increased in cardiomyocytes during cardiomyocyte hypertrophy in vitro. 26914935_3 intriguingly, we found that another target of mir-99a fgfr3 was down-regulated in lenti-99a-gfp group. 26148557_1 high-throughput quantitative confocal immunofluorescence demonstrated a significant inhibition of mmp2, p38, tnfalpha and vegf in msdacs in the presence of hsa-mir-125b mimic. in addition, we observed a marginal decrease in grb10 and stat3 expression with hsa-mir-125b mimic. 26148557_2 similarly, functionally mimicking hsa-mir-27b resulted in the profound inhibition of fosb, kras, p38 and ptpn3. 26148557_3 interestingly, mimicking hsa-mir-27b did not inhibit the expression of egfr and vegf in msdacs. 26148557_4 on the other hand, msdacs transfected with hsa-mir-20a exhibited significant inhibition of ask1, mmp2, mmp3/10, ptpn3 and vegf . 26148557_5 we did not see any consistent inhibition of creb and stat3 at least with the mimic for hsa-mir-20a. 26148557_6 moreover, hsa-mir-93 mimic exhibited statistically significant inhibition of mmp2, mmp3/10, ptpn3 and stat3 in this setting. 26148557_7 next, msdacs transiently transfected with inhibitors for hsa-mir-1224-3p or hsa-mir-1260 and examined for the alterations in protein targets. 26148557_8 inhibiting hsa-mir-1224-3p resulted in the significant induction of adamts-1 and creb. 26148557_9 like-wise, inhibiting hsa-mir-1260 markedly induced adamts-1 and ask1 . 26148557_10 however, inhibiting hsa-mir-1260 did not result in the induction of fosb and akt-1 in this setting. 22592534_1 mir-145 exhibited inhibitory role in tumor angiogenesis, cell growth and invasion and tumor growth through the post-transcriptional regulation of the novel target n-ras and vegf-a. 22592534_2 taken together, these results demonstrate that mir-145 plays important inhibitory role in breast cancer malignancy by targeting n-ras and vegf-a, which may be potential therapeutic and diagnostic target. 22592534_3 importantly, the mir-145-mediated repression of vegf expression was reversed by re-expression of n-ras, suggesting the pathway from mir-145 to n-ras and further to vegf is important . 22592534_4 taken together, these results suggest mir-145 inhibits tumor growth and angiogenesis in vivo through targeting n-ras, vegf-a and their downstream signaling molecules. 22592534_5 in summary, mir-145 suppresses tumor angiogenesis and growth due to targeting n-ras and vegf signaling. 26706910_1 in the present study, we observed that mir-27b was significantly increased in cervical cancer cells and tissues, and upregulation of mir-27b was negatively associated with its direct target, cadherin 11 . 26706910_2 in the present study, it was revealed that mir-27b was overexpressed in cervical cancer cells and tissue specimens, and that downregulation of mir-27b inhibited cervical cancer cell growth and invasion. 26706910_3 cdh11 is a direct and functional target of mir-27b and was found to be involved in the functional effect of mir-27b on cell proliferation and invasion. 26706910_4 moreover, upregulation of mir-27b by transfection with mimics in the hela cells reduced the mrna and protein levels of cdh11, while downregulation of mir-27b by transfection with an inhibitor in the c33a cells increased mrna and protein levels , indicating that mir-27b directly targets the cdh11 3'utr. 26706910_5 altogether, these data suggest that cdh11 is a functional target of mir-27b, involved in mir-27b-induced proliferation and invasion of cervical cancer cells. 19187610_2 the 3'-utr of hla-a gene had one partially complementary site for mir-181a and mir-181a might down-regulate the expression of hla-a. 26490981_1 using fluorescence reporter assays, we confirmed that six1 was a direct target of mir-188 in oscc cells. 26490981_2 these results indicated that mir-188 binds to the six1 3'-utr region directly and downregulates six1 mrna expression. 26490981_3 furthermore, fluorescent reporter assays demonstrated that mir-188 directly bound to the six1 3'-utr region, suggesting six1 as a direct target of mir-188. 18521848_1 altered expression of mir-17-5p, mir-106a, and egfl7 was associated with pathological tumor features of poor prognosis. 18521848_2 downregulation of mir-106a predicted shortened dfs and os . 18521848_3 mir-17-5p correlated with dfs only at early stages . 18521848_4 inverse correlations were found between mir-17-5p and mir-106a levels and their target expression, e2f1 . 18521848_5 inverse correlation between mir-17-5p and mir-106a and e2f1 levels supports e2f1 as a target mrna for the two mirnas. 21152985_1 these results demonstrate that mir-103 is involved in porcine preadipocyte differentiation and may act through the putative targetgene rai14. in contrast, the presence of the mir-103 inhibitor resulted in an increase in the rai14 transcript at both the mrna and protein levels. 21152985_2 the data described above strongly suggest that the biologically relevant mirna-targetinteractions between mir-103 and rai14 gene occur during the porcine preadipocyte differentiation process. 21152985_3 this is consistent with the hypothesis that rai14 is mir-103 targetgenes. 24970806_1 mir-942 decreases trail-induced apoptosis through isg12a downregulation and is regulated by akt.. 19641183_1 apoptotic activity was diminished in motn1 cells transduced with mir-21 whereas western analysis showed that levels of pten and pdcd4 were reduced and those of pakt were increased in the transductant cells. 19641183_2 aso-21 and aso-155, which reduced expression of both mir-21 and mir-155, levels of pten and ship1 were increased. 19641183_4 this finding suggests that forced expression of mir-21 further enhances pakt expression via down-regulation of pten. 26871282_1 these results suggest olfm4 is downregulated by mir-486-5p, which contributes to ovarian cancer tumorigenesis. 26871282_2 ho8910-pm and skov3 cells transfected with mir-486-5p mimics, had decreased olfm4 mrna levels, indicating that olfm4 is a potential target of mir-486-5p in ovarian serous adenocarcinoma . 26871282_3 the estrogen receptor antagonist ici 182 780 or knockdown of eralpha attenuated e2-induced changes in mir-486-5p expression in skov3 cells , supporting a potential inhibitory effect of eralpha signaling on mir-486-5p expression. 24256616_1 our study reveals additional mirs, particularly mir-10b and mir-151a, that could be directly regulated by the p53-family of transcription factors and contribute to the tuning of p53-induced responses 22505583_1 phb is a target of mir-27a in pca cells. 22505583_2 increasing mir-27a expression results in reduced phb mrna and protein levels, and increased expression of ar targetgenes and prostate cancer cell growth. 22505583_3 his suggests that levels of phb and mir-27a are closely linked in pca, supporting phb as an endogenous target of mir-27a in this disease. 22505583_4 taken together, these data confirm that mir-27a target phb-3'-utr in pca cells through seed region binding, leading to transcript disruption and/or translational inhibition and loss of phb protein, which can be abrogated through addition of mir-27a aso. 22505583_5 together, these data indicate that mir-27a targeting of phb increases ar activity in pca cells through loss of phb corepressive activity, and that manipulation of mir-27a alters pca cell growth. 22892391_1 mir-204 direct targeting of the 3'-utr of bcl2 and ntrk2 was confirmed. 22892391_2 mir-204 is a novel predictor of outcome in neuroblastoma, functioning, at least in part, through increasing sensitivity to cisplatin by direct targeting and downregulation of anti-apoptotic bcl2. 22892391_3 we determined that mir-204 directly targets the 3'-utr of both the anti-apoptotic gene bcl2 and the oncogene ntrk2 . 22892391_4 direct targeting of 3'-utrs was determined by cloning of the 3'-utr seed region and a mutated seed region into separate psicheck-2 vectors for both bcl2 and ntrk2.mir-204 22892391_6 in conclusion, mir-204 has emerged as an independent predictor of survival in neuroblastoma, functioning, at least in part, through direct targeting and downregulation of key chemotherapy resistance proteins ntrk2 and bcl2. 22292036_1 importantly, mir-16 targeted the 3'-untranslated region of smrt and caused translational suppression of smrt. the oligonucleotide corresponding to mir-16, but not mir-143-3p, primed first strand synthesis from the smrt mrna , suggesting that a mir-16 binding site exists in the smrt 3'-utr. 22292036_2 the mir-16 precursor had no effect on luciferase activity in cells transfected with the mutant smrt 3'-utr construct in h69 cells, suggesting that mir-16 may suppress translation of smrt mrna by binding to the 3'-utr region of smrt. 22292036_3 coupled with mir-16-mediated translational suppression of smrt mrna, our data suggest that mir-16 represses smrt expression through translational suppression, not rna degradation. 22292036_4 the above data suggest that mir-16 upregulation is required for lps-induced downregulation of smrt protein in h69 and u937 cells. 22292036_5 together, these data suggest that mir-16 regulates lps-stimulated nf-kappab transcriptional activation through repression of smrt. 21892175_1 we show here that hcmv mir-us4-1 specifically downregulated erap1 expression during viral infection.accordingly, 23027131_2 treatment of fer1 cells with 4oht in the presence of mek inhibitor u0126 revealed that the upregulation of mir-24 by ras is almost completely abolished when mapk pathway was inhibited , strongly suggesting that mir-24 induction could have a role in wnt4 repression. 26692942_1 we further validated satb1 was a direct target of mir-495 in rcc. 26692942_2 moreover, satb1 was identified as a direct target of mir-495 and re-expression of satb1 reversed the mir-495-induced inhibition of cell proliferation and migration. 26692942_3 our results suggest that satb1 is a functional downstream target of mir-495 in rcc. 25560389_1 mir-125a-3p regulates glioma apoptosis and invasion by regulating nrg1. 26282001_1 runx2 was chosen as a favored target gene of mir-218 by using open access software, target scan, because a conserved sequence was found in the 3'-utr of runx2 mrna with a perfect match to the seed region of mir-218. 26282001_2 luciferase reporter assays showed that upregulation of mir-218 decreased the relative luciferase activity of runx2 3'-utr noticeably but no difference to the mutated 3'-utr. 26282001_3 similar results were found that mir-218 overexpression significantly reduced the endogenous mrna and protein of runx2 . in contrast,blocking the expression of mir-218 increased the expression of runx2 . 26282001_4 these results indicated that runx2 is a direct target of mir-218 and is negatively regulated by mir-218 in a549 cells. 25833697_1 qrt-pcr and western blot analyses were used to further determine whether mir-139-5p could regulate zeb1 and zeb2 at the mrna and protein levels. 25833697_2 our results illustrate that overexpression of mir-139-5p inhibited zeb1 and zeb2 at the mrna and protein levels . 25833697_3 these data suggest that mir-139-5p directly targets zeb1 and zeb2. 25833697_4 these results suggest that mir-139-5p regulates gbm cell migration and invasion by acting through zeb1 and zeb2. 20219920_1 human papillomaviruses modulate expression of microrna 203 upon epithelial differentiation to control levels of p63 proteins. 20219920_2 one target of mir-203 is the p63 family of transcription factors. 26144048_1 these findings implied that the overexpression of ddx6 in colorectal tumor was regulated at least in part by mir-124. 26144048_2 these findings altogether suggested that mir-124 targeted ddx6, thus contributing to the down-regulation of ddx6 at the translational level in colon cancer cells. 26144048_3 actually, the down-regulated mir-124 could cause the overexpression of ddx6 at least in part in colon cancer cells. 26297548_1 all these findings suggested that mir-454 probably regulates cell growth through pdk1. 26297548_3 using bioinformatic analysis, mtt assays, colony formation and cell cycle assay, we found that mir-454 acted as a tumor suppressor in gbm, suppressing gbm cell proliferation was due to inhibit 3-phosphoinositide-dependent protein kinase-1 , and then regulating cell proliferation and cell cycle regulators, down-regulation of cyclin d1 and p-prb and p21 was up-regulated. 26272747_1 the array identified that overexpression of let-7e-5p significantly decreased expression of col1a1, col1a2, col3a1, col24a1, col27a1, itga1,itga4, scd1 and thbs1 mrnas by more than 2-fold , suggesting that let-7e-5p targets at least those nine ecm gene mrnas. 26272747_2 we examined whether stretch could alter expression of let-7e-5p and its target ecm genes in vitro. 26272747_4 overall, these data confirm that dysregulation of the mechanomir let-7e-5p is accountable for the up-regulation of ecm proteins in the diaphragm muscle from mdm mouse. 22213190_1 in silico target gene prediction methods indicated that mir-22 and mir-29b may target the human, mouse,and rat mthfr and mat1a genes, respectively. 22213190_2 figure 6 shows that transfection of trl1215 cell with pre-mir-29b or pre-mir-22 resulted in a decrease in the levels of mat1a and mthf. 23612742_1 consistent with its anti-apoptotic target bcl2, mir-205 promoted apoptosis in prostate cancer cells in response to dna damage by cisplatin and doxorubicin in the prostate cancer cell lines pc3 and lncap. 22634495_1 microrna-10a target chl1 and promotes cell growth, migration and invasionin human cervical cancer cells, subsequently, chl1 is confirmed as a target of mir-10a and is negatively regulated by mir-10a at mrna and protein levels. 22634495_2 direct regulation of chl1 by mir-10a through binding to the 3'utr of chl1 mrna. 26497556_1 mir-107 downregulates cpeb3 expression by directly targeting the cpeb3 3'-utr. 26497556_2 these data indicate that mir-107 directly targets the cpeb3 3'-utr, thereby reducing cpeb3 expression. 21510944_1 slc7a11 is identified as a direct target of mir-26b and its expression is remarkably increased in both breast cancer cell lines and clinical samples. 21510944_2 therefore, mir-26b directly regulates slc7a11 expression by binding cs1 and cs2 in the slc7a11 3'-utr. 21510944_3 all these data support that slc7a11 is a direct target of mir-26b. 20700123_1 mir-489 negatively regulates ptpn11 expression. 20700123_3 disruption of this interaction may lead to the deregulation of mir-489-ptpn11 signalling in hscc. 20700123_5 immunoblotting confirmed that ptpn11 protein expression was significantly decreased in mir-489 transfectants . 26807671_1 the expression levels of mir-34b- 5p and mir-34c- 5p in mdd patients were significantly higher than these in healthy controls, while the notch1 gene expression were significantly lower in mdd patients compared to normal controls . 26807671_2 notch1 gene were significantly lower in mdd patients ,was negatively correlated with the expression mir-34c-5p and mir-34b-5p. 26788506_2 additionally, mbd2 silencing could partly reverse the effect of mir-221 on cell migration and invasion. 26788506_3 in conclusion, downregulation of mir-221 inhibits cell migration and invasion at least partially through targeting mbd2 in the human oscc cell line um1. 26788506_5 these results suggest that mir-221 affects migration and invasion in um1 cells through regulation of its target mbd2. 26718613_1 to validate the fact that mir-28-5p targets erk2, the protein levels of erk2 in hepg2 cells were measured following transfection with the mir-28-5p mimic or inhibitor. 26718613_2 western blotting indicated that transfection with the mir-28-5p mimic significantly reduced the expression levels of erk2 in hepg2 cells, whereas the mir-28-5p inhibitor resulted in elevated levels of erk2 following 48 h of transfection . 26718613_3 these results indicate that mir-28-5p is a key mediator in the regulation of the translation of erk2. 26718613_4 mir- 28- 5p upregulates abca1 expression through the inhibition of erk2. 22895706_1 computational analyses, corroborated empirically, demonstrate that the top mrna target of both microrna-132 and microrna-212 is tmem106b; both micrornas repress tmem106b expression through shared microrna-132/212 binding sites in the tmem106b 3'utr. 22895706_2 tmem106b is regulated by mir-132 and mir-212. 22895706_3 mir-132 and mir-212 are dual repressors of tmem106b through shared binding sites in the 3'-utr. 22895706_4 we expressed these tmem106b 3' utr mutants in hek293 cells and assayed their expression levels under the regulation of endogenous mir-132/212. 22895706_5 together, these results provide empirical confirmation of the computationally predicted regulation of tmem106b by mir-132 and mir-212. 26800505_1 we also validated tp53inp1 as a target of mir-125a in nucleus pulposus cells using a dual luciferase reporter system, and the transfection of mir-125a significantly reduced the expression of tp53inp1. 26800505_2 the luciferase reporter system was used to validate tp53inp1 as a target gene of mir-125a, which was confirmed by the following in vitro analysis, showing that tp53inp1 mrnaand protein expression levels were similarly but significantly down regulated by mir-125a mimics and anti-tp53inp1 sirna compared with the scramble control. 26800505_3 consistent with the hypothesis that mir-125a negatively regulates the expression of tp53inp1, we found that mrna and protein expression levels were comparable between ct and tt, whereas the expression of tp53inp1 was much lower in cc than in the ct and tt groups . 18504438_1 mir-34a caused the most significant suppression of cell growth through increased apoptosis and decreased dna synthesis in neuroblastoma cell lines with mycn amplification. 18504438_3 furthermore, we demonstrated that mycn is a direct target of mir-34a. 18504438_4 finally, using a series of mrna expression profiling experiments, we identified other potential direct targets of mir-34a, and pathway analysis demonstrated that mir-34a suppresses cell-cycle genes and induces several neural-related genes. 18504438_5 this study demonstrates one important regulatory role of mir-34a in cell growth and mycn suppression in neuroblastoma. 26622832_1 of these, mir-17-5p, -19a-3p, -19b-3p, -21-5p, -130b-3p, -221-3p and -222-3p were previously shown to target pten, indicating that the regulation of pten expression through these mirnas induces apoptosis in cultured brain tumor cells. 26622832_2 a previous study showed that mir-21 acted together with mir-155 in a downstream signaling pathway in natural killer cell tumors and cell lines, and inhibited the expression of the target pten and pdcd4 . 26622832_3 furthermore, the increased expression of mir-221-3p and -222-3p inhibited that of pten in glioma cells . 26622832_4 these findings suggest that the expression of mir-17-5p, -19a-3p, -19b-3p, -21-5p, -130b-3p, -221-3p and -222-3p enhanced and inhibited the pten expression in the 60-gy-irradiated gscs in the present study. 22442671_1 luciferase reporter and western blot assays confirmed that rala is a direct target of mir-181a. 22442671_2 overexpression of mir-181a effectively suppresses cell growth and induces g2-phase arrest and apoptosis partially by targeting rala in leukemic k562 cells. 26385595_2 the luciferase activity was substantially reduced by mir-34a, which suggested that mir-34a directly binds to the 3'utr of atp5s. 26385595_3 the results showed that mir-34a significantly inhibit the protein level of atp5s . 26385595_4 these data indicated that mir-34a can decrease atp levels by binding to the 3'utr of atp5 s. the overexpression of atp5s rescued the atp reduction induced by mir-34a . 26385595_5 these data indicated that resistin can downregulate atp by the direct targeting of 3'utr of atp5s by mir-34a. 22384930_1 in addition, the inhibition of mir-193 could increase ing5 expression . 22384930_2 according to the mirna database, the target site in the 3'-utr of ing5 is conserved in vertebrates and partially complementary to mir-193 . 26191184_1 mir-365 directly targets and inhibits nrp1. 26191184_2 taken together, these results indicate that nrp1 is a direct downstream target for mir-365 in mm cells. 26692922_1 in addition, h19 derived microrna-675 was down-regulated in the glioma, and cdk6, a pivotal regulator in cell cycle, was a target of microrna-675. 26692922_2 collectively, these findings strongly indicate that cdk6 is a direct target of microrna-675 in the glioma. 26692922_3 luciferase assay was also performed to further confirm that cdk6 is a direct target for h19 derived microrna-675. 26692922_4 thus, cdk6 is a potential target of microrna-675. 26617742_1 to verify whether irs-1 is a direct target of mir-126 in glioma, a human irs 3- utr fragment containing the binding sites of mir-126 or the mutant sites was cloned to were cloned into the psicheck2 vector . 26617742_2 we found that the expression of irs-1 was downregulated both mrna level and protein level in mir-126 treated cells. 26617742_3 these results suggest that mir-126 directly targets irs-1 by binding its seed region to their 3'-utrs in glioma cells. 20215506_1 interestingly, we found that expression of mir-375 inhibited expression of pdk1, which is a direct target of mir-375, followed by suppression of akt phosphorylation. 20215506_2 this result was reproducible in the additional two independent experiments , suggesting that mir-375 target the mir-375 binding sequence at the 3'-utr of 14-3-3味. 20215506_3 these results suggest that downregulation of pdk1 and 14-3-3味 is involved in mir-375-搃nduced apoptosis. 20215506_4 it has recently been reported that mir-375 directly target pdk1 and suppresses its expression in pancreatic -beta cells . 22952991_1 we demonstrated that, in human umbilical vein endothelial cells, both mir-421 and mir-30c directly interacted with pai-1 mrna to inhibit the expression of the associated protein. 22952991_2 mir-421 and mir-30c inhibit serpine 1 gene expression in human endothelial cells. 22952991_3 as a consequence, we pursued our investigations on the influence of rs1050955 on mir-421's binding to serpine1 3'-utr region and on serpine1 expression in huvec. 22952991_4 among the mirnas predicted to bindthe serpine1 region where rs1050955 lies, we demonstrated that only the mir-421 was jointly expressed with serpine1 in a variety of cell types. 22952991_5 mir-421 was further shown to directly interact with pai-1 mrna to inhibit the expression of the associated protein in huvec. 26766915_1 taken together, these results suggest that itgb1 is a functional target of mir-29c in pc cells.. these results demonstrated that mir-29c can directly inhibit itgb1 expression in pancreatic cells. 22661574_2 however, in gram-negative species, glms expression is regulated by two srnas glmz and glmy, a dual regulatory system that requires hfq for activity. 22661574_3 relative expression levels of glms were monitored as the ability to upregulate glms synthesis individually by srnas glmz and glmy with varying c-terminal extensions of hfq. 22661574_4 therefore, the necessity of the c-terminal region of hfq for glms activation by srnas, glmz or glmy was tested using the gfp fusion system. 21533114_1 we identified lmo0302 and chia as direct targets of lhra. 21533114_2 we show here that lhra acts as a post-transcriptional regulator of lmo0302 and chia by interfering with ribosome recruitment, and we provide evidence that both lhra and hfq act to down-regulate the expression of lmo0302 and chia. 21533114_3 furthermore, in vitro binding experiments show that hfq stimulates the base pairing of lhra to chia mrna. 11845212_3 deletion of a 3.7-kb imprint control element that contains the air promoter releases paternal-specific silencing of three genes, slc22a2 and slc22a3 that are located upstream, and igf2r that is located downstream. 23805317_3 found that mir-34a and mir-34c target platelet-derived growth factor receptor alpha and beta , cell surface tyrosine kinase receptors that induce proliferation, migration and invasion in cancer.moreover, 18351803_1 it is somewhat unusual for two srnas to act upon the same target mrna, and despite their seeming homology, these two srnas employ different molecular mechanisms and function hierarchically to activate glms expression: glmz directly activates glms translation via disruption of an mrna structure that inhibits translation, whereas glmy controls the processing of glmz to prevent the inactivation of this direct activator.the 18922924_1 we report here pdef as a novel targetfor mir-204 and mir-510 and describe for the first time a mechanism for the loss of pdef protein expression during breast cancer progression. 18922924_2 cotransfection with either mir-204 or mir-510 further reduced the luciferase activity to 55% and 35%, respectively . 18922924_4 these results show that mir-204 and mir-510 posttranslationally regulate endogenous pdef mrna, most likely through a mechanism of translation inhibition. 18922924_5 taken together, these data suggest that mir-204 and mir-510 levels are elevated in invasive breast cancer and that these levels are inversely correlated to pdef protein expression. 26467022_1 mir-622 directly targets map4k4 in hcc. 17110380_1 using the human breast cancer cell line skbr3 as a model for erbb2 and erbb3 dependence, infection of these cells with retroviral constructs expressing either mir-125a or mir-125b resulted in suppression of erbb2 and erbb3 at both the transcript and protein level. 17110380_2 luciferase constructs containing the 3'-untranslated regions of erbb2 and erbb3 demonstrated 35% less activity in mir-125a- and mir-125b-expressing cells relative to controls. 17110380_3 extrapolating their growth rates out to day 6 indicated an apparent 25% slower growth rate by the mcf10a-125a and mcf10a-125b cells relative to the control mcf10a-puro cells, suggesting a mild negative influence by these mirnas on cellular proliferation mechanisms independent of erbb2 status and possibly related to the reported tumor suppressing function of mir-125a and mir-125b . 17110380_5 1a, the maximum free energy predicted hybridization configurations between the putative 3'-utr mir-125 targetelements in erbb2 and erbb3 and the seed sequences in mir-125a or mir-125b all exhibit similar stabilities at deltag ~-14 kcal/mol, determined by mfold analysis and consistent with authentic mirna targeting . 26050992_1 during osteogenic induction, mir-26a expression levels increased gradually, while tob1 expression was decreased in both sham-msc and ovx-msc . 26050992_2 taken together, these data indicate that tob1 was the direct functional target of mir-26a under osteoporotic conditions. 23319046_1 mir-7 is known to targetthe epidermal growth factor receptor 3' untranslated region , and indeed, qki-deficient u343 cells had reduced egfr expression and decreased erk activation in response to egf. 23319046_2 we cloned the mir-7 binding sites and flanking sequences from the egfr 3'-utr into a firefly luciferase reporter that we named pluc:egfr3'-utr . 26629104_1 using a combined bioinformatic analysis and rt-qpcr, we determined that the ccne1 gene is targeted by mir-16-1 in cc cells. 26629104_2 siha, caski, and hela cells demonstrated an inverse correlation between mir-16-1 expression and ccne1 mrna level. 26629104_3 thus, mir-16-1 post-transcriptionally down-regulates ccne1 gene expression. 19843643_1 these results, together with the results of western blotting, suggest that at least vim, smyd3, and iqgap1, and abce1 are novel possible targets for mir-124-mediated and mir-203-mediated translational downregulation in hepatocytes, respectively, and that activation of these molecules through methylation-mediated silencing of those two mirnas may contribute to the pathogenesis of hcc. 26644266_1 luciferase activity assay showed that mir-302 inhibited bcrp expression by targeting the 3'-untranslated region of the bcrp mrna. 26644266_2 these findings suggest that mir-302 inhibits bcrp expression via targeting the 3'-utr of bcrp mrna. 26644266_3 mutations in the putative binding site in the 3'-utrs of the bcrp mrna abolished the inhibitory effect of mir-302a, mir-302b, mir-302c, mir-302d, and mir-302s on luciferase activity , further suggesting that mir-302a, mir-302b, mir-302c and mir-302d directly targeted bcrp via the putative binding site in the 3'-utrs of bcrp mrna. 26644266_4 the results suggest that mir-302s decreased bcrp mrna levels by reducing rna stability. 26644266_5 mir-302 reduced bcrp expression via targeting the 3'-utrs of bcrp mrna. 26317788_2 moreover, our data demonstrated that sry-related high mobility group-box gene 9 , the essential regulator of the process of cartilage differentiation, was the direct target gene and functional mediator of mir-494 in chondrosarcoma cells. 26317788_3 thirdly, using human chondrosarcoma cell line sw1353 transfected with mir-494 mimics, we validated that sox9 was downregulated at mrna and protein level, which was further confirmed by the luciferase reporter assay, suggesting that mir-494 directly binded to sox9 3'-utr in chondrosarcoma cells. 21831363_1 mir-491-5p suppressed glioma cell invasion via targeting mmp-9 directly. 21831363_2 the above results indicated that mir-491-5p could induce invasion inhibition by directly targeting mmp-9 in glioma cells. 21831363_3 fig. 4 - mir-491-5p directly target the 3'-utr of mmp-9 mrna in glioma cell line. 21831363_4 the above results indicated that mir-491-5p could induce invasion inhibition by directly targeting mmp-9 mrna in glioma cells. 23011132_1 both mir-212 and mir-132 directly target the anti-hypertrophic and pro-autophagic foxo3 transcription factor and overexpression of these mirnas leads to hyperactivation of pro-hypertrophic calcineurin/nfat signalling and an impaired autophagic response upon starvation. 26191142_1 these findings suggest that notch1 and jagged1 are direct targets of mir-34c. 26191142_2 the results showed that overexpression of mir-34c significantly decreased the mrna expression levels of notch1 and jagged1 . 26191142_3 consistently, western blot results showed that the protein expression of notch1 and jagged1 was markedly decreased by mir-34c overexpression. 26402430_1 mir-140-5p downregulates vegfa by directly targeting its 3'utr. 26402430_4 vegfa is a functional target of mir-140-5p. 20562915_1 ectopic overexpression of mir-23b in normal renal cells resulted in striking downregulation of pox, whereas pox expression increased markedly when endogenous mir-23b was knocked down by its antagomirs in renal cancer cells. 26822534_1 mir-224 directly targets gsk3-beta and sfrp2. 26822534_2 clinical data confirmed gsk3-beta or sfrp2 are the direct targets of mir-224 26770454_2 accordingly, our data proved that sirt7 is a directly target gene of mir-125b by the prediction method, targetscan, and luciferase assay. in conclusion, our investigation confirmed that mir-125b was a tumor suppressor gene in hcc by regulating its target gene, sirt7. 24294352_2 moreover, when ec-109 cells were treated with mir-577 mimics the expression of tsga10 decreased. 24294352_3 conversely, when kyse-105 cells were treated with mir-577 inhibitor, the expression of tsga10 increased. 26440600_1 among tested mirnas, mir-16 showed the strongest negative effects on both app and bace1. 20813833_1 several cell death regulators were identified as downstream target of mir-21, including pten and akt. 20813833_2 thus, these results identify the p85 subunit of pi3k, which is an upstream regulator of akt activation , as a mir-21 target 26054975_1 mir-573 represses tspan1 expression by directly targeting its 3'-utr. 26054975_2 taken together, these results demonstrate that mir-573 represses tspan1 expression by directly targeting its 3'-utr. 26054975_3 these results provide further support that tspan1 is a functional target of mir-573. 26837847_1 mechanistic analyses indicate that the mir-130 family directly targets phosphatase and tensin homolog deleted from chromosome 10 , resulting in the upregulation of fak and akt phosphorylation. 26837847_2 we show here for the first time that the mir-130 family is upregulated in bladder cancer clinical specimens and coordinately promotes bladder cancer cell migration and invasion through the phosphorylation of focal adhesion kinase as well as akt by regulating pten expression or sub-cellular localization. 26837847_3 collectively, the data strongly indicate that the mir-130 family negatively regulates pten protein expression in bladder cancer cells, promoting their migration and invasion properties. 26837847_4 we report here that the mir-130 family molecules are novel negative regulators of pten expression in bladder cancer. 26297836_1 thus, gga-let-7a-5p and gga-let-7b post-transcriptionally regulate tgfbr1 and lin28b. 26297836_2 therefore, gga-let-7a-5p and gga-let-7b mirnas mark their target mrnas for degradation in undifferentiated blastodermal cells. 20395557_1 inhibition of let-7d in vivo caused decreased cdh1 and tjp1 expression; increased collagen, hmga2, and acta2 expression; and thickening of alveolar septa. 20395557_2 let-7d inhibition caused a significant decrease in expression of the epithelial markers cdh1 and tjp1 and a significant increase in col1a1 and hmga2 expression in the lungs . 22496754_1 furthermore, ccnd2 and ccne2, as possible targeted genes of mir-26a, were up-regulated. 22496754_2 together, these results suggest that ccnd2 and ccne2 but not ccne1, cdk6, ccnd1 or ccnd3 are potential targeted genes of mir-26a. 22496754_3 we showed that mir-26a over-expression inhibits expression of ccnd2 and ccne2, and conversely, anti-expression of mir-26a leads to an enhanced expression of ccnd2 and ccne2 in both mrna and protein level in vivo, suggesting ccnd2 and ccne2 are probably the targeted genes of mir-26a. 21953646_3 we showed effective targeting of the cdkn1a 3' utr by mir-17/106b in hl cell lines in a luciferase reporter assay and up-regulation of p21 protein levels upon anti-mir-17 treatment of km-h2 cells. 25945589_1 spred-1, spry1 and rasa1 are direct targets of the microrna-132/212 family. 25945589_2 as microrna functions by inhibiting its targets, we reason that knockdown of spred1, spry1 and rasa1 should have similar effect as overexpression of mir132 and mir-212. 25945589_3 mir-132/212 family modulates ras-mapk signalling by targeting spred1, spry1 and rasa1 in vivo. 26835423_2 a significant reduction in the ccdc6 mrna levels has been observed in the cells transfected with mir-130b-3p, in comparison with a scrambled oligonucleotide . 26835423_3 this result indicates mir-130b-3p has an effect on ccdc6 mrna degradation. 26858153_1 forced expression of mir-373 down-regulates the expressions cd44 and tgfbr2, while knockdown of cd44 and tgfbr2 presents the similar phenotype as mir-373 overexpression, suggesting that cd44 and tgfbr2 are functional targets of mir-373, down-regulation of cd44 and tgfbr2 by mir-373 are partly responsible for the migration, and invasion suppressive role of mir-373 in u251. 26858153_2 we also identified cd44 and tgfbr2 as the functional targets of mir-373, overexpression of mir-373 down-regulated the expression of cd44 and tgfbr2, partly contributing to its migration and invasion suppressive role. 26858153_3 these data suggested that both cd44 and tgfbr2 are the direct targets of mir-373. 19942685_1 experiment results strongly suggest that lhra regulates expression of lmo0850 mrna at the posttranscriptional level, by base pairing to a region located upstream from the active start codon.the 19942685_2 binding of lhra to lmo0850 mrna effectively blocks the formation of both the upstream and downstream translation initiation complex.importantly, 23861775_1 collectively, these results indicate that cks2 is a direct target of mir-26a. 23861775_2 our data indicate that mir-26a functions as a growth suppressive mirna in ptc, and that its suppressive effects are mediated mainly by repressing cks2 expression. 23861775_3 finally, we examined the expression levels of mir-26a and its target gene, cks2, in ptc and normal thyroid tissue. in our study, a variety of results indicated that cks2 is a direct target of mir-26a in tpc-1 cells: a seed binding site sequence for mir-26a was identified in the 39utr of cks2 mrna; cks2 39utr luciferase reporter activity was decreased by overexpression of mir-26a but not by mut-mir-26a, contains a mutation in the seed binding site of mir-26a; cks2 mrna and protein levels were decreased by mir26a overexpression in tpc-1 and cgth w3 cells, and this effect was attenuated by anti-mir-26a; silencing cks2 expression in tpc-1 cells had similar cell-growth suppressive effects to those of overexpression of mir-26a; cks2 overexpression rescued the growth suppressive effect of mir-26a to an extent similar to that of anti-mir-26a; and a significant inverse correlation exists between mir-26a and cks2 in clinical ptc specimens. 25803820_1 mir-20a directly targets and inhibits atg7 and timp2. 25803820_2 taken together, these results indicate atg7 and timp2 are direct downstream targets for mir-20a in siha cells. 25538945_1 mirna-140-5p remarkably downregulated the erbb4 expression in ec9706 and te-1a cell lines. 25538945_5 taken together, mirna-140-5p could act as a potential molecular target in erbb4 overexpressing escc cell lines paving the way for effective esophageal cancer treatment. 18834857_1 among the four genes assayed, luciferase activity with irs-1 3'-utrs was significantly inhibited by mir-126 , while luciferase activity with mutated irs-1 3' -utr reporter was not inhibited . 18834857_2 this data suggested that mir-126 target irs-1. 18834857_3 we did not find any effects of psilencer-mir-126 on irs-1 mrna level , while irs1 protein level decreased dose-dependently by psilencer-mir-126 transfection . 26235810_1 suggesting pdk-1 as a potential target for mir-375 in bmpac 23537271_3 huh7.5.1 cells transfected with plasmid pegfp-core or pegfp were used to detect theeffects of hcv core protein on mir-122 expression, the results showed that core protein could down-regulate themir-122 expression level in a time- and dose- dependent manner, and reduced the susceptibility of huh7.5.1 cell tohcv. 26805019_1 these effects of mir-155 on autophagy were related to suppression of gene and protein expression of key autophagy regulators including ulk1, foxo3, atg14, atg5, atg3, gabarapl1, and map1lc3. 26805019_2 mir-155 regulates autophagy by suppressing map1lc3, gabarapl1, atg3, atg5, atg14, ulk1 and foxo3. 26805019_3 it is conceivable that mir-155 influences the expression of map1lc3, atg14 and ulk1 by suppression of the transcriptional factor foxo3. furthermore, we demonstrated that increased levels of mir-155 inhibit gabarapl1, atg3, atg5, atg14, foxo3, map1lc3, and ulk1 expression, and drastically suppress autophagy independently of its regulation on rictor expression and on mtor signalling. 22049153_2 on the basis of previous work indicating mir-16 to be a pleiotropic regulator of are-containing mrnas, and its ability to target reporter constructs bearing the cox-2 3'-utr , we sought to determine whether mir-16 may be involved in are-mediated regulation of cox-2. 22049153_4 1a, expression of mir-16 in il-1-beta-搕reated hela cells reduced cox-2 mrna approximately 2-fold. 22049153_5 this mir-16-揹ependent loss of cox-2 mrna was reflected in a similar approximately 2-fold decrease in cox-2 protein expression and associated pge2 synthesis . 22049153_6 the ability of mir-16 to attenuate pge2 synthesis was consistent with specific targeting of cox-2 because expression of cox-1 mrna or protein were not impacted by mir-16 . 22049153_7 taken together, these results indicate that mir-16 facilitates endogenous cox-2 mrna association with risc leading to regulation of cox-2 mrna and protein overexpression. 22049153_8 these results were validated by assaying for an established target of mir-16, bcl-2, in ago2 immunoprecipitates in which mir-16 was expressed . 22049153_10 1e, bcl-2 mrna was enriched in mir-16/ago2 immunoprecipitates, whereas capture of the negative control gapdh mrna was unchanged. 22049153_11 to ensure that the effects of mir-16 were dependent on the presence of the cox-2 3'-utr, a reporter construct containing a 1.8-kb cox-2 promoter was cotransfected into hela cells with either mir-16 or the negative control. 22049153_13 2d, overexpression of mir-16 had no effect on cox-2 promoter or control sv40 promoter/enhancer activity, indicating mir-16 targeting of cox-2 is 3'-utr dependent and not a consequence of indirect transcriptional interference. 22049153_14 these results substantiate that targeted downregulation of cox-2 by mir-16 occurs via the 3'-utr to promote enhanced mrna degradation. 25530132_1 mir-142 regulates rac1 expression at the transcriptional and translational levels by directly targeting its 3'utr. 25481039_1 down-regulation of the slc8a1 gene, most likely mediated by its regulator mir-223, can lead to reduced calcium levels in peca and, consequently, to suppression of apoptosis and increased tumor cell proliferation. 19628698_1 to study the possibility that alpha-syn expression in the substantia nigra could be regulated by mir-7, we investigated the levels of mature mir-7 in this region and several other regions of the mousebrain by quantitative real-time rt-pcr analysis . 19628698_2 these results suggest that mir-7 negatively regulates alpha-syn expression in neurons. 26056431_1 these results indicate that ra not only had the ability to inhibit expression of stat3 transcription factor, but also had the ability to suppress phosphorylation of stat3, suggesting that ra may affect the il-6/stat3 pathway via mir-155. 26058485_1 we focused on the targets of mir-429 in colon cancer cells, and the luciferase reporter assay data confirmed that pak6 was a target gene of mir-429 in lovo colon cancer cells . 26058485_2 we also found that transfection with pre-mir-429 led to a decreased mrna and protein expression of pak6 , suggesting that mir-429 negatively mediated the expression of pak6 in colon cancer cells. 26058485_3 the expression of pak6 was positive in colon cancer tissues, but negative in their matched adjacent normal tissues, suggesting that pak6 acts as an oncogene in colon cancer.taken 26058485_4 together,the results suggested that cofilin acts a downstream effector in mir-429-mediated colon cancer cell migration and invasion. 22507670_1 smad4, a common mediator of the tgf--beta pathway, is identified as a direct target of mir-146a by harboring a mir-146a binding sequence in the 3'-utr region of its mrna.expression of mir-146a led to a reduction of cellular responsiveness to tgf--beta and an increase of apoptosis rate in chondrocytes. 25202363_2 the expression of the cdk6 protein in the mgc-803 cells was downregulated by upregulating the expression of mir-449a. 22374434_1 our in vitro data demonstrated that mir-15b and/or mir-16 regulated bcl2 at the protein level. 22374434_2 inhibition of mir-15b and/or mir-16 reduced hepatic apoptosis and tnf production. 25101050_1 we searched the 3'-utr of p21 and found that it contains one binding site for mir-17 .3a. to prove the targeting effect of mir-17 on p21, we designed a luciferase assay in which the 3'-utr sequence of p21 was cloned into a luciferase vector and co-transfected with mir-17. 25101050_2 when a mutated mir-17 containing mutations in the seed sequence, which is responsible for binding to p21 3'-utr, was used, the targeting effect of mir-17 was abolished .3b. these results indicate that p21 is a specific target of mir-17. 25101050_3 these results suggest that mir-17 silencing regulation of p21 likely controls np population in embryonic cortices. 26299367_2 after showing the importance of mir- 214 in regulating cslc stemness, we showed that the direct target of mir- 214 is ctnnbip1, an essential player in the wnt signaling pathway. 26299367_3 taken together, these results suggest that ctnnbip1 is a direct target gene of mir- 214. in addition, we revealed that ctnnbip1, a negative regulator of wnt/ beta-catenin signaling, is a target gene of mir- 214. 26631117_1 luciferase reporter and western blot assays showed that il-10ralpha expression is directly regulated by mir-15a, mir-185, and mir-211, either alone or in combination. 26631117_2 an inverse expression pattern between il-10ralpha, on one side, and mir-15a, mir-185, and mir-211 on the other one was also shown in melanoma samples. 26455824_1 we identified that mir-21 directly interacted with the 3 ' -untranslated region of the suppressor of dimethylarginine dimethylaminohydrolase 1 by dual-luciferase assay. 26455824_2 our data suggest that mir-21, which is known to be over-expressed in renal fibrosis, significantly up-regulates apoptosis of hk-2 cells, as well as increasing interstitial deposition-related genes a-sma, type i collagen, and fibronectin, and decreases endothelial cell marker endothelial cadherin , and we also identified that mir-21 directly interacts with the 3 ' -untranslated region of ddah1, while ddah1 effectively inhibits the hk-2 cells apoptosis and interstitial deposition by suppressing the wnt/b catenin signaling activation. 26455824_3 therefore, these results demonstrate that ddah1 is a direct target of mir-21. 21200031_2 to examine the possibility of mir-125b targeting igf-ii, we asked whether mir-125b regulated igf-ii expression. 21200031_3 both mrna and protein levels of igf-ii increased during c2c12 differentiation as previously reported , which correlated well with the drop of mir-125b levels at the same time . 21200031_4 the efficacy of delivering oligonucleotides into muscles might not be optimal , but the observed effects are significant and fully consistent with mir-125b targeting igf-ii during muscle regeneration in vivo. 21200031_5 most importantly, when the predicted mir-125b seed region in the 3- utr was mutated, the mutant reporter no longer responded to mir-125b , strongly suggesting that the predicted site is a bona fide target of mir-125b and it is solely responsible for mir-125b targeting of the igf2 3- utr. 21200031_6 these results suggest that mir-150 is unlikely to regulate igf2, and they also serve as negative controls that validate the reporter assays , identifying mir-125b as a bona fide igf2 regulator. 21200031_7 although our observations do not definitively eliminate the possibility of other mirnas and/or target sites being involved in regulating igf2 3- utr, collectively they strongly support the notion that mir-125b plays a predominant role in the regulation of igf-ii during skeletal myogenesis. 25613939_1 using luciferase activity assay, we identified sirt1 is a direct target of mir-204-5p. 25613939_2 furthermore, we showed down-regulation of mir-204-5p promotes high-glucose attenuation of corneal epithelial wound healing via up-regulation of sirt1 in ins2akita/+ mice. 25613939_3 together, these results confirmed that sirt1 is a direct target of mir-204-5p and is regulated by mir-204-5p. 21618519_1 in summary, the data presented here indicate that let-7 regulates the expression of imp-1 causing destabilization of mdr1 mrna and increased sensitivity to taxane-induced cell cycle arrest and cell death in adr-res cells. 26134263_1 these results suggested that mir-130a directly targets runx3. 26134263_2 we found that runx3 expression was significantly increased in mir-130a-low-expressing gastric cancer cell lines 24205079_1 mirna-132 and mirna-214 suppress srebp-1c and ldlr by targeting specific site within the 3- utr of srebp-1c and ldlr, respectively. 24205079_2 overexpression of pre-mirna-132 and pre-mirna-214 significantly decreased the luciferase activity of the 3'-utr of the srebp-1c and ldlr reporter containing micrna-132 and mirna-214 binding sites, respectively. 25272045_1 these data suggest that mir-410, mir-495, and mir-214 specifically inhibit the fhl1 3'-utr, but that the effects of mir-146a and mir-146b-5p may be non-specific or at sites other than their predicted target sites. 25272045_2 interestingly, fhl1 mrna expression also was decreased by mir-410, but not mir-495 or mir-214 . 25272045_3 these results suggest that mir-495 and mir-214 inhibit fhl1 at the protein level, but that mir-410 functions to inhibit mir-410 via a mechanism that occurs prior to fhl1 translation. 22941339_1 our previous findings suggested that upregulation of hsa-mir-127 in ebv-positive bl may determine the downregulation of blimp-1 and xbp-1 and the consequent persistence of bcl-6 expression, as well as the gc phenotype in b cells that have already differentiated towards memory b cells in terms of ig mutation pattern. 23716467_1 the transfection of mir-17-5p mimics or sirna-p21 reversed the effect of bortezomib on htb-111 and ishikawa cells, indicating that mir-17-5p may mediate the function of bortezomib by targeting p21 in endometrial cancer cells. 26149640_1 mir-21 regulated the expression of mkk3 via 3 ' utr. 26149640_2 mir-21 targets mkk3 in vivo and in vitro, inhibiting the downstream factors il-6 and tnf-a. 26149640_3 the regulation of mir-21 on mkk3 mrna and protein was confirmed in hk-2 cells. in conclusion, the present study has shown that mkk3 is the target gene of mir-21. 25714700_3 data on mechanism suggest that up-regulation of mir-153 level promotes cell proliferation via the down regulation the expression of pten or foxo1, which attenuates the proliferation of cancerous cells. 19370765_2 we have found the c allele of rs28521337, located in a functional target site for mir-485-3p in the truncated isoform of ntrk3, to be significantly associated with the hoarding phenotype of ocd. 19370765_3 we have also identified two new rare variants in the 3'utr of ntrk3, ss102661458 and ss102661460, each present only in one chromosome of a patient with pd. the ss102661458 variant is located in a functional target site for mir-765, and the ss102661460 in functional target sites for two mirnas, mir-509 and mir-128, the latter being a brain-enriched mirna involved in neuronal differentiation and synaptic processing. 19370765_5 these data implicate mirnas as key posttranscriptional regulators of ntrk3 and provide a framework for allele-specific mirna regulation of ntrk3 in anxiety disorders. 23547260_1 mir-33a* specifically target the 3'-utr of human npc1, crot, irs2, src1, src3, and nyfc, while mir-33b* specifically target the 3'-utr of human nfyc. 23547260_2 here, we identify seven mir-33a* and two mir-33b* targetgenes and show that mir-33a* and mir-33b* overexpression leads to their posttranscriptional repression. 18632605_2 in contrast, pgl3 carrying the mutant 3'utr of hif-1alpha with 4-bp deletions in the core of seed sequences of each targetsite for mir-17-5p and mir-20a did not show obvious decreases in luciferase activities when transfected into clones #31 and #57. 18632605_3 we also analyzed whether such negative regulation of hif-1alpha could be indirectly provoked by hypoxia-induced up-regulation by mir-17-92. 18632605_4 transient transfection of c-myc clearly led to up-regulation of mir-20a and down-regulation of hif-1alpha in beas2b cells. in conclusion, we identified hif-1alpha as a novel targetfor mir-17-92 using itraq tagging and multidimensional lc and ms/ms analyses. 18632605_5 transient transfection of c-myc clearly led to up-regulation of mir-20a and down-regulation of hif-1a in beas2b cells. in this study, we identified hypoxia-inducible factor -1alpha as a novel direct targetfor mir-17-92 through global expression profiling by mass spectrometric analysis using an isobaric tagging reagent, itraq, combined with bioinformatic targetprediction. 22431718_1 luciferase reporter assay further verified direct target association of mir-145 to specific sites of the irs1 and irs2 3'-untranslated regions. 22431718_2 here, we describe recurrent underexpression of mir-145 in hepatocellular carcinoma and the identification of a biological pathway by which mir-145 exerts its functional effects in liver tumorigenesis. it is therefore probable that mir-145 inhibits hcc cell proliferation along the igf pathway, at least in part through simultaneous targeting of irs1 and irs2, and an indirect influence on igf1r expression. 26150475_1 there was a significant negative correlation between the relative levels of mir-21 and pdcd4 mrna in malignant melanoma tissues, as shown by spearman-rank correlation coefficient analysis. 26150475_2 as shown in table 1, an elevated mir-21 relative level and reduced pdcd4 mrna relative level were both significantly correlated with an increased tumour size, a higher clark classification level and the presence of lymph node metastases in malignant melanoma. 26111756_1 dnmt1 is the target of mir-148a. 26111756_2 expression levels of mir-148a in osteosarcoma tumor or non-tumor tissue measured by quantitative pcr. the level of dnmt1 in osteosarcoma tumor or non-tumor tissue measured by quantitative pcr 21501375_1 at 104 weeks of age, hf-prone mice had significantly reduced expression levels of mir-17, mir-18a, mir-19a, mir-19b, mir-20a, and mir-92a-1 as compared to 12-week littermates , coinciding with the observed increased presence of their targets tsp-1 and ctgf. 21501375_2 aging of hf-resistant mice, on the other hand, was accompanied by significantly enhanced expression of these mirnas, except for mir-17 and mir-20a . 21501375_3 together, these data suggest that regulation of ctgf and tsp-1 is the result of the shared expression of mir-18a, mir-19a, and mir19b, enabling modest changes in mirna expression to control transcriptional repression. 21501375_4 these findings confirm the expression profiles in aged hf-prone mice and again suggest that mir-18a, mir-19a, and mir-19b could transcriptionally repress ctgf and tsp-1 levels in cardiomyocyte aging and hf at old age. 21501375_5 these results show that regulation of ctgf and tsp-1 by mir-18a and mir-19b is uniquely restricted to the cardiomyocyte. 21501375_6 thus, in concordance with ctgf and tsp-1 regulation by mir-18a and mir-19b in cardiomyocytes, these data strongly imply that mir-18a and mir-19b contribute to the induction of collagen synthesis in aged cardiomyocytes via the regulation of the pro-fibrotic ctgf and tsp-1. 19931509_1 over-expression of mir-200a significantly downregulated, whereas knock-down of mir-200a upregulated, the protein expressions of both zeb2 and ctnnb1. 19931509_2 in this study, we used a combined bioinformatics and experimental approach to identify that zeb2 and ctnnb1 are the two functional downstream target of mir-200a. 19931509_3 mir-200a inhibits npc cell growth, migration and invasion by targeting different mrnas, zeb2 and ctnnb1. 19931509_4 these data show that ctnnb1 mrna is one of direct target of mir-200a. 23152446_1 sirna knockdown of computationally predicted targets followed by mutational analyses revealed that let-7 and mir-18 down-regulate acvr1b and smad2, respectively, to attenuate nodal responsiveness and bias blastomeres to ectoderm and mesoderm fates. 23152446_2 let-7 and mir-18 control germ layer fate by negatively regulating tgfb/nodal signaling by directly targeting acvr1b and smad2, respectively. 23152446_3 let-7 and mir-18 directly target acvr1b and smad2 3' utrs. 23152446_4 our findings-initially from functionally screening a whole-genome mir library-that let-7 and mir-18 target acvr1b and smad2 to control mesoderm at the expense of endoderm reveal an unanticipated and evolutionarily conserved role for mirs that is nonredundant with known regulators of germ layer specification. 18451220_2 down-regulation of c-myc was observed in two cell lines in response to mir-184 inhibitor. 18451220_4 overexpression of mir-184 might play an oncogenic role in the antiapoptotic and proliferative processes of tongue scc. 11251852_1 at least two small rnas, dsra and rpra , participate in the positive regulation of rpos translation. 11251852_2 unlike dsra, rpra does not have an extensive region of complementarity to the rpos leader.it is dsra but not rpra which is important for minimal medium expression of rpos.mutations in the gene interfere with the induction of rpos after osmotic shock when dsra is absent, demonstrating a physiological role for rpra. 26868851_1 the above results demonstrated that igf-1 r, amy-1, and pgc-1b were primary targets of mir-139 in regulating the activity of glioma cells. 20827722_1 further studies revealed that lin28b was a downstream target of mir-125b in hcc cells as mir-125b bound directly to the 3' untranslated region of lin28b, thus reducing both the messenger rna and protein levels of lin28b. 20827722_2 lin28b was a direct downstream targetfor mir-125b in hcc cells. 20827722_3 the expression level of lin28b mrna was down-regulated by mir-125b using real-time pcr assays. 20827722_4 taken together, these findings indicate that lin28b is a direct downstream targetfor mir-125b in hcc cells. 20827722_5 together, our results indicate that reduction of lin28b through sirna interference has similar effects on the hcc cells to those induced by mir-125b, suggesting that lin28b may act as a downstream functional mediator for mir-125b. 20827722_6 taken together, these findings show that lin28b reintroduction could abrogate mir-125b-搃nduced cell growth arrest and metastasis suppression, suggesting that lin28b is a functional mediator for mir-125b in hcc cells. 21530489_1 in the current study, our data demonstrated that ifn-gamma stimulation and fas activation suppressed dicer processing and let-7 microrna biogenesis, while let-7 microrna strongly inhibited fas expression by directly targeting fas mrna. 26636539_1 pten has previously been confirmed as a direct target of mir-382 in hif-1alpha-stimulated vascular endothelial cells . 26636539_2 while mir-382 inhibitor increased pten expression at protein level in nctc1469 liver cells. 22802531_3 we identified socs36e as a target of bantam in growth control. 22802531_4 taken together, these results suggest that bantam acts directly to limit socs36e expression in vivo. 25712526_1 mirna-30a is a potent inhibitor of autophagy by downregulating beclin-1. 26165231_1 thus, the effect of mir-29b to down-regulate the mouse rnls 3'-utr activity was consistent in both these cell types. 26165231_2 validating specific interactions between mir-29b/mir-146a and mouse rnls transcript. 21447182_1 transfection experiments showed that bovine npm2 protein expression is reduced in hela cells expressing mir-181a compared to control cells without mir-181a, indicating that translation of npm2 is repressed by mir-181a. 21447182_2 a mir-181a binding site in bovine npm2 3'utr was identified . 21447182_3 the inverse correlation between mir-181a and npm2 expression during early embryogenesis further supports our hypothesis that npm2 might be down-regulated by mir-181a. 21447182_4 quantification of npm2 protein expression using densitometry confirmed that co-expression with mir-181a decreased the level of npm2 protein , indicating that translation of npm2 is repressed by mir-181a. 25204970_1 in addition, neuropilin1 was identified as a target of mir-338 in oscc cells and inversely correlated with mir-338 in oscc tissues. 25204970_2 taken together, mir-338 might inhibit growth and metastasis of oscc cells by targeting nrp1. 25204970_3 finally, we further identified neuropilin1 as a direct target of mir-338 in oscc cells. in addition, we identified that nrp1 was a direct target of mir-338 in oscc cells. 20486857_2 in addition, anti-mir-98 and anti-let-7i markedly increased socs4 3'utr-associated luciferase reporter translation . 20486857_3 in contrast, mir-98 and let-7i precursors significantly decreased the luciferase activity . 20486857_4 the above data suggest that mir-98 and let-7 targetsocs4 3'utr resulting in posttranscriptional suppression. 20486857_5 taken together, the above data suggest that c. parvum infection decreases expression of mir-98- and let-7 through activation of the tlr4/myd88 signaling pathway to regulate socs4 protein expression in biliary epithelial cells. 26845057_1 we analyzed the 3'utr of mfn2 using the target scan program and found apreferred candidate mirna, mir-761, that targets three puta-tive binding sites within the 3'utr of mfn2. 26845057_2 we mutated the three candidate binding sites andfound that the wild-type 3'utr of mfn2 exhibited a lowertranslation level in the presence of mir-761, whereas themutated 3'utr did not show a significant response to mir-761 . 26845057_3 taken together,these results indicate that mfn2 is a direct target of mir-761in hcc cells and that mir-761 downregulates mfn2 expres-sion by directly targeting its 3'utr. 20644734_2 mir-148 was shown to affect mitf mrna expression in melanoma cellsthrough a conserved binding site in the 3'utr sequence of mouse and human mitf.in 20644734_3 addition we confirm the previously reported effects of mir-137 on mitf. 20644734_4 these results indicate that mir-148 is able to downregulate mitf expression by binding to the 148/152b binding site. 20644734_6 our results therefore confirm the role of mir-137 in regulating mitf expression. 20644734_7 these results show that the mir-137 and mir-148 have the same effects on expression of the endogenous mitf gene as seen using the luciferase reporter assay. 20644734_8 when the cells were transfected with either mir-137, mir-148 or simultaneously with both mir-137 and mir-148, mitf protein levels were reduced. 26893028_1 in addition, we demonstrated that pten was the direct target of mir-92b and reduce of pten expression partially rescued the inhibitory effects of mir-92b inhibitor on the glioma cells. 26893028_2 taking together, these data showed that the mir-92b could bind to pten 3'-utr and mir-92b is able to downregulate the activity of pi3k/akt signal pathway. 26893028_3 these results implied that the mir-92b directly targets pten who further suppresses pi3k/akt signaling pathway in glioma cells. 25451224_1 mir-25 also increased cell viability, decreased early apoptosis, and downregulated the accumulation of mutant ataxin-3 protein aggregates in sca3/mjd cells. 26562549_1 moreover, we revealed that glycogen synthase kinase-3-beta was a direct target of mir-1290 and pol treatment could result in wnt pathway down regulation. 26562549_2 no appreciable inhibitory effect was observed when mir-1290 mimics or nc mimics co-transfected with the empty vector or the mutant reporter , indicate that the gsk3-beta is a direct target of mir-1290. 21890451_1 we then determined that the tumor suppressor dicer1 is a target of hsa-mir-31. 21890451_2 the immunoblot and reporter assays independently confirmed that dicer1 is a target of hsa-mir-31 in human cells. 21890451_3 interestingly, quantification of dicer1 mrna indicated a certain downregulation of the level of dicer1 mrna expression in sk-mes-1 cells transfected with hsa-mir-31 as compared with control microrna, even though the p value is not significant, suggesting that hsa-mir-31 may act mainly by inhibiting the translation of dicer1 . 21890451_4 these results indicated that the expression of dicer1 is inversely correlated with hsa-mir-31 level in scc tumor tissues. 21890451_5 we showed that hsa-mir-31 directly target the dicer1 3'-utr and repressed the expression of dicer1 but not ppp2r2a or lats2. 20382729_1 to determine whether fli-1 could be directly targeted by mirna145, we engineered the pgl3 luciferase reporter vector to contain either the human wild-type full-length human fli-1 3'-utr or its mutant form harboring a 6-base deletion in the four putative mirna145 targetsites . in hek293 cells, cotransfection of the luciferase reporters with a retroviral vector expressing the mirna145 resulted in a 60% reduction in luciferase expression from the wild-type fli-1 3'-utr reporter. 19070389_1 the exogenous expression of mir-320 or mir-204 could negatively regulate mcl-1 or bcl-2 expression and facilitate chemotherapeutic drug-triggered apoptosis. 22246100_1 our findings attribute stress-inducible cognitive impairments to cholinergic-mediated induction of mir-132 and consequently suppressed ache-s, opening venues for intercepting these mir-132-mediated damages. 22246100_2 therefore, if ache-s suppression could by itself prevent stress-inducible cognitive decline, tgr mice should show no such decline; but if mir-132 increases are the cause, then these mice should present a stress phenotype. 22246100_3 neuronal ache and the gtpase activator p250gap are both targets of mir-132. 22246100_4 these findings are compatible with the hypothesis that the inter-individual variability in hippocampal mir-132 is inversely interlocked with that of p250gap. 22246100_5 our analysis thus attributes the observed stress-inducible cholinergic hyper-excitation to the feed-forward regulation of mir-132 and ache transcripts, and shows that avoiding p250gap reduction and the corresponding breadth of inter-individual variability in mir-132 associates with stress-inducible cholinergic hyper excitation and cognitive impairments . 17427289_4 rybb readily forms complexes with the ompn 5'utr fragment, while rybb complex formation is considerably weaker with the ompc and ompd 5'utrs. 25591738_2 tead4 mrna was confirmed as a direct target of mir-512; likewise, mir-373 was found to target rela and pik3ca mrna directly. 25591738_3 our results imply that mir-512 and mir-373 exert cell-autonomous and non-autonomous tumor-suppressive effects in lung cancer cells, where their re-expression may benefit epigenetic cancer therapy.cell 26191168_1 to elucidate whether epha2 is a potential downstream target gene of mir-26b in hcc cells, the mirna target prediction websites www.microrna.org 26191168_2 and targetscan were used to identify a conserved mir-26b-binding site in the 3'-utr of epha2 mrna. 26191168_3 co-transfection of mir-26b mimics suppressed the luciferase activity of the reporter containing wild-type epha2 3- utr sequence, but failed to inhibit that of mutated epha2 by dual-luciferase reporter assay. 26191168_4 inversely, luciferase activity was significantly increased in the cells transfected with mir-26b inhibitors, but did not change in the mut 3'-utr cells . 26191168_5 these data suggest that epha2 may be a direct functional target of mir-26b in hcc. 12719555_1 we speculate that tmevpg1 may down-regulate the expression of ifng because both genes are expressed in the same subset of lymphocytes , they have opposite expression patterns following stimulation, and the tmevpg1 gene and its human ortholog encode a noncoding rna. 12719555_3 furthermore, the pattern of expression of tmevpg1 during stimulation is a mirror image of that of ifng. 20716523_1 editing of a mutation-containing pri-mir-bart6 found in daudi burkitt lymphoma and nasopharyngeal carcinoma c666-1 cell lines suppressed processing of mir-bart6 rnas.mir-bart6-5p 19843843_3 targeting of fgfr3 was investigated using protein expression following mir knock-down and a luciferase reporter assay. 23585871_1 our results highlight that mir-125b modulates the p53 network by hindering the down-regulation of mdm2, thereby affecting p53 and its target genes p21 and puma to a degree sufficient to inhibit apoptosis. 19427019_1 taken together, these data indicated that mir-124 negatively regulated slc16a1 at both transcript and protein levels in mbs. 19427019_3 these results provided further evidence that slc16a1 is a direct target of mir-124. 20080666_1 reporter assays in which the pten, rb1, or map3k2 3'-utrs were fused to gfp or luciferase conifirmed that the 3'-utrs of these mrnas confer regulation by mir-26a .in 20080666_2 addition, mir-26a overexpression or the mir-26a mimic increased u87 gbm cell growth despite the absence of pten . 20080666_3 the proliferative effect of mir-26a was antagonized by overexpression of pten or rb1 . 22968638_1 based on computational predictions, further studies demonstrated that e2f3 was a target of mir-351 in myoblasts. 22968638_2 further evidence has been provided that e2f3 is a direct target of mir-351, thus revealing a novel role of this mirna in the regulation of muscle regeneration. 22968638_3 taken together, these results indicate that mir-351 represses e2f3 expression in myoblasts by translational inhibition. 26799422_1 linc00152 expression was inversely correlated with p15 and p21 mrna and protein levels. 26799422_2 linc00152 knockdown markedly increased levels of p15 and p21 in xenograft tumors . 26799422_3 these data suggest that linc00152 contributes to gc development by inhibiting p15 and p21. 26799422_4 p15 and p21 mrna levels were detected using qpcr in bgc-823 and sgc-7901 cells after si-ezh2 transfection, and protein levels. 24991827_1 yy1 regulated sqstm1 expression through the epigenetic modulation of the transcription of mir372 which was found to target sqstm1 directly. 24991827_2 during nutrient starvation, yy1 was stimulated to promote sqstm1 expression and subsequent autophagy activation by suppressing mir372 expression. 25472877_1 ccng1 and mef2d, two putative mir-122 targets, were found to be downregulated by oa treatment. 26349988_1 we examined several putative mir-101 target genes identified by microarray analysis and demonstrated that mir-101 directly targets cxcl12, which play important roles in cafs. 26349988_2 the mutant construct exhibited a lower inhibitory effect on luciferase activity compared with the cxcl12 3'-utr vector after mir-101 cotransfection , suggesting that mir-101 suppressed the transcription activity of the cxcl12 gene bytargetingthe bindingsite in the 3'utr of cxcl12 mrna independently. 26349988_3 collectively, these findings suggest that mir-101 regulates the expression of cxcl12 post-transcriptionally. 18483394_1 in the present studies, we have confirmed, as predicted, that mir-16-1 regulates ccnd1 protein expression and that truncation of the 3' utr occurs in mcl cell lines preventing proper mir-16-1 regulation of ccnd1. 18483394_2 to prove that this truncation alters both mir-16-1 binding sites within the ccnd1 mrna, we cloned the truncated version from all 4 mcl cell lines. 18483394_3 this truncation occurs 328 bp immediately downstream of the stop codon and eliminates 2863 bp of the distal ccnd1 3'-utr including both mir-16-1 binding sites . 18483394_4 these data are consistent with the hypothesis that truncated ccnd1 3'-utr is unresponsive to regulation by mir-16-1. 22235305_1 using a recently established model in which apoptosis of ctcl cell lines is induced by notch-1 inhibition by 纬-secretase inhibitors , we found that mir-122 was significantly increased in the apoptotic cells. 22235305_3 surprisingly,mir-122 overexpression decreased the sensitivity to the chemotherapy-induced apoptosis via a signaling circuit involving the activation of akt and inhibition of p53. 25154741_1 furthermore, we identified and validated matrix metalloproteinase-2 as a direct target of mir-130b. 25154741_2 taken together, our data reveal for the first time that mir-130b exerts a suppressive effect in prostate cancer metastasis through down-regulation of mmp2. the effects of mir-130b on tumor metastasis could be attributed to the decreased expression of mmp2, which has been identified as a new target for mir-130b. 25154741_3 thesefindings indicate that mir-130b negatively regulates mmp2 expression by directly binding to its 3 0 -utr. 22265691_2 the results indicate that overexpression of mir-18a leads to a 29% decrease in ptf1a mrna levels and a 62% decrease in ptf1a protein levels relative to controls, while inhibition of mir-18a partially rescues the expression of ptf1a protein . 22265691_4 mir-18a represses the expression of ptf1a via binding the 3'-utr target sequence of ptf1a mrna. 22265691_5 these results indicate that mir-18a represses ptf1a expression by directly targeting the 3'-utr of ptf1a mrna. 22265691_6 the relative expression pattern of mir-18a and ptf1a in pancreatic cells suggests that mir-18a exerts a role in pancreatic progenitors and acinar cells via regulation of ptf1a expression. 26633713_1 mtfr1 is a direct target of mir-324-5p, and mir-324-5p attenuates mitochondrial fission, cardiomyocyte apoptosis and myocardial infarction by suppressing mtfr1 translation. 26633713_2 these results indicate that mir-324-5p can specifically regulate mtfr1. 26633713_4 these data suggest that mir-324-5p targets mtfr1 in the cascades of mitochondrial fission and apoptosis. 25433291_1 among these predicted targets, we were particularly interested in the anti-apoptotic factor api-5. there was only one putative mir-1 binding site in the api-5 3'-utr, which was identified by the targetscan and pictar algorithms. 25433291_2 the putative base-pairing and secondary structure of mir-1 bound to the target site in the api-5 3'-utr. 25433291_3 stical analysis confirmed an approximate 3-fold up-regulation of api-5 protein levels in hcc samples compared with matching normal liver tissue samples . in contrast, mir-1 expression, as detected by real-time pcr, was significantly reduced in liver tumors relative to their matched controls . 25433291_4 these results indicated that the abundance of api-5 protein and level of mir-1 were inversely related in both hcc tissues and normal liver tissues. 26820227_1 thereby providing additional evidence of direct interaction between mir-187 and 3'-utr region of sox4, nt5e and ptk6 . 26820227_2 sox4, nt5e and ptk6 are direct targets of mir-187 22431589_2 tsc1 3' utr contains one predicted mir-25 and -32 binding site. 25736362_1 antxr2 inhibition by mir-124 promoted jnk activation and induced autophagy. 23690337_1 these results reinforce the note that pten is the target gene of mmu-mir-200a. 23690337_2 these results suggest that pten is the target gene of mmu-mir-200a, and the level of pten protein is negatively regulated by mmu-mir-200a by inhibiting mrna translation. 21625861_1 eight genes including trim41, sox13, slc25a4, sema4f, rpusd2,plekhg6, ccnd2, and btbd3 were identified as hsa-let-7i target. 20013340_1 mir-15a/16-1 and mir-15b/16-2 clusters have been shown to play very important roles in regulating cell proliferation and apoptosis by targeting cell cycle proteins and the antiapoptotic bcl-2 gene. 21804560_1 we next validated expression changes in three key pcat-1 targetgenes whose expression is upregulated upon pcat-1 knockdown in lncap and vcap cells, the latter of which appear less sensitive to pcat-1 knockdown likely due to lower overall expression levels of this transcript. 21804560_2 qpcr expression of three pcat-1 targetgenes after pcat-1 knockdown in vcap and lncap cells, as well as following ezh2 knockdown or dual ezh2 and pcat-1 knockdown in vcap cells. 19652553_1 mnt mrna contains multiple mir-210 binding sites in the 3' utr and its knockdown phenocopied mir-210 overexpression. 19652553_2 to test whether mir-210 regulation of mnt is direct, we fused the 3'utr of mnt to a luciferase reporter. 19652553_3 as shown in figure 4b, co-transfection with mir-210 but not mir-185 specifically decreased luciferase levels from the reporter. 19652553_4 furthermore, western blot analysis indicated that mir-210 overexpression effectively reduced mnt protein levels in all cell lines tested, and the strongest effect was observed in hct116 dicerex5 cells which have dampened endogenous micrornas . 19652553_5 furthermore anti-mir210 increased mnt levels in two cell lines with relatively high levels of endogenous mir-210 . 21853155_1 the mechanism whereby let-7a expression regulates esft growth is shown to be mediated by its targetgene hmga2, as let-7a overexpression and hmga2 repression both block esft cell tumorigenicity. 21853155_2 consistent with the notion that hmga2 is a target of let-7a expression of hmga2 was decreased in tumors derived from let-7a expressing esft cells . 21853155_3 these observations uncover the important effector role of hmga2 in esft cell tumorigenicity and identify let-7a-mediated repression of hmga2 as a key mechanism in the reduction of tumor forming capacity by tumor cells upon let-7a restoration. 23152059_2 mir-204 targeted bcl-2 messenger rna and increased responsiveness of gc cells to 5-fluorouracil and oxaliplatin treatment. 23152059_3 ectopic expression of bcl-2 protein counteracted mir-204 pro-apoptotic activity in response to 5-fluorouracil. 23152059_4 altogether, these findings suggest that modulation of aberrant expression of mir-204, which in turn releases oncogenic bcl-2 protein activity might hold promise for preventive and therapeutic strategies of gc. 23152059_5 these findings mirror that aberrant expression of bcl-2 in gastric tumors associates with downregulation of mir-204. 20052801_1 bioinformatics analysis identified kshv mirna binding sites for mir-k12-3 and mir-k12-7 within the 3'utr of the basic region/leucine zipper motif transcription factor c/ebp, a known regulator of il-6 and il-10 transcriptional activation. 25578780_2 further, there was reciprocal repression between xist and mir-152. 25578780_3 mechanistic investigations defined the direct binding ability of the predicted mir-152 binding site on the xist. 21148433_1 this result indicates that pak1 may be a target of mir-126a. 21148433_2 figure 7.mir-126a and mir-126b repress pak1 reporter differently. 21148433_6 b, alignment of mir-126a/b with target site of spred1 3'-utr or pak1 3'-utr . 21148433_7 the luciferase assay showed that mir-126b inhibited the spred1 reporter to the same extent as mir-126a did, but repressed the pak1 reporter more than mir-126a , whereas mir-155 did not affect these 2 reporters. 21148433_9 mir-126b has a similar binding site to mir-126a with spred1 3'-utr . 21148433_10 however, it was different for pak13'-utr, the minimum free energy with mir-126b is lower than with mir-126a . 21148433_11 taken together, these results indicate that pak1 is a direct target of mir-126a and mir-126b in vascular endothelial cells of zebrafish. 21148433_12 this result suggests that pak1 is a downstream target of mir-126a/b, indicating that mir-126a/b regulates vascular integrity through modulating pak1 expression during zebrafish development. 23598416_1 we identify the misfolded protein chaperone grp78, as well as the unfolded protein response transducers endoplasmic reticulum to nucleus signaling 1 and activating transcription factor 6 as direct targets of mir-199a-5p, and show that endogenous mir-199a-5p represses the 3'untranslated regions of their mrnas. 26884939_1 the over expression of mir-101 can remarkably reduce the in vitro proliferation and invasion ability of ovarian cancer cells through the down-regulation of socs-2. 26884939_2 all of these results suggest that mir-101 probably plays an important role in the genesis and development of ovarian cancer by regulating the expression of its target gene socs-2. 24336073_1 collectively, our data provide a novel mechanism whereby p53 represses chk1 and wee1 expression, at least partially, via upregulation of mir-16 and mir-26a and thus sensitizes tumour cells to genotoxic therapies. 18941111_1 transfection of antisense oligonucleotides against mir-17 and mir-20a into jeko-1 led to up-regulation of cdkn1a/p21, resulting in decreased cell growth with g to s arrest. 26239806_1 furthermore, a luciferase reporter assay revealed that high mobility group at-hook 2 was a direct target of mir-485-5p and that the overexpression of hmga2 reversed the effects of mir-485-5p on cell metastasis and emt. in the present study, we examined hmga2 as a novel direct target of mir-485-5p. 26239806_2 using a luciferase reporter assay and western blot analysis, we demonstrated that mir-485-5p suppressed hmga2 expression by directly targeting the 3'utr of hmga2. 26109086_1 interestingly, when we overexpressed mirna in endothelial cells, igf-1r and c-myb expression were downregulated, suggesting that igf-1r is a target for mir-150 that may be regulated indirectly through c-myb downregulation. 24572376_1 we identified mir-24 as a negative regulator of p16ink4a. 23559009_1 together, these results suggest that mutant p53 specifically and preferentially binds to the mir-27a promoter region from nucleotides -2899 to -2675. 23559009_2 we found that the transcriptional activity of the mir-27a promoter was repressed by p53-273h but not by wild-type p53 in a dose-dependent manner . 23559009_4 induction of mir-27a reduced the reporter activity of the construct containing wild type 3'-utr of egfr. 23559009_5 mir-27a also showed the similar repressive effect on mut2 reporter activity. 23559009_7 these indicate that mir-27a is targeted to the region 1 of egfr 3'-utr. 17890317_1 expression of mir-29s is inversely correlated to dna methyltransferase 3a and -3b in lung cancer tissues, and that mir-29s directly target both dnmt3a and -3b.the enforced expression of mir-29s in lung cancer cell lines restores normal patterns of dna methylation, induces reexpression of methylation-silenced tumor suppressor genes. 26854715_4 we therefore performed luciferase reporter assays to determine whether foxp1 expression could indeed be directly regulated by mir-504. 26854715_5 to further demonstrate the regulation of foxp1 by mir-504 in glioma cells, qrt-pcr and western blot analyses were performed to detect alterations of mrna and protein expression levels, respectively, of foxp1 after mir-504 transfection. 26854715_6 both foxp1 mrna and protein expressions decreased significantly following mir-504 overexpression in u87 and u373 cells. 26854715_7 taken together, these results suggested that foxp1 is directly targeted and negatively regulated by mir-504 in glioma cells. 26918338_1 figure 1g shows the two complementary binding sites of mir-129-3p in the 3'-utr of the human and rat cp110 mrnas. 26918338_3 conversely, inhibition of mir-129-3p by transfection of anti-sense molecules resulted in increased cp110 protein levels 21412257_2 taken together, these results demonstrate that mir-125b directly regulates fgfr2 expression by binding to the four targetsites in the 3'-utr of fgfr2 mrna. 21412257_3 the concurrent upregulation of fgfr2 and downregulation of mir-125b in psoriasis supports the regulation of fgfr2 by mir-125b in the skin. 21412257_4 this suggests that the regulation of keratinocyte differentiation by mir-125b is mediated through target other than fgfr2. 22241070_1 reporter gene assays confirmed mir-212 to targetthe 3'-utr region of abcg2. in contrast mir-212 downregulated abcg2 protein expression under short-term and long-term conditions, and it was confirmed to bindto the abcg2 3'-utr. 22241070_2 to the best of our knowledge, this is the first time that mir-212 was identified to interact with abcg2. 21119662_2 to examine the inhibitory effect of mir-584 on protein level, we did western analysis at 72 h after mir-584 transfection into a-498 and 769-p cells. 21119662_3 we observed that protein levels of rock-1 in mir-584-transfected a-498 and 769-p cells were significantly decreased compared with mir control . 21119662_4 rock-1 is a mir-584 targetgene. 21119662_6 the mir-584 or mir control were transfected into a-498 cells. 20483747_1 overexpression of mir-21 and mir-148a also markedly reduced dnmt1 expression . 20483747_2 together, these data indicated that the upregulation of mir-21 and mir-148a expression can inhibit dnmt1 expression. 20483747_3 mir-21 indirectly downregulates dnmt1 expression by targeting its upstream regulator, rasgrp1. 20483747_4 mir-148a directly downregulates dnmt1 expression by targeting the protein coding region of its transcript. 20483747_5 all of these data suggested that mir-148a directly inhibited dnmt1 protein expression through interaction with the protein coding region of dnmt1 transcript. 20483747_6 together, our data suggested that mir-21 indirectly downregulated dnmt1 expression by targeting its upstream regulator rasgrp1. 23868013_1 these results clearly demonstrated that mir-433 negatively regulated azin1 expression by directly targeting the 3- -untranslated region of azin1. 23868013_2 although renal expression of mir-433 and fibrotic markers increased in ligated kidneys at 7 days after uuo, azin1 expression was greatly reduced at both rna and protein levels , suggesting that azin1 expression was negatively correlated with mir-433 expression and occurrence of renal fibrosis. 21533284_1 let-7 target genes, including hmga2 are specifically deregulated in the c5 molecular subtype of high-grade serous cancers. 21533284_3 we observed highly specific deregulation of individual members of the mycn-lin28b-let7 pathway in c5 tumours, as well as a broader set of mycn and let7 transcriptional targets. 21533284_4 lin28 and lin28b negatively regulate let-7 levels by binding to the terminal loops of the precursors of let-7 family mirna, thereby blocking processing into mature mirnas , , , . 24099915_1 mechanistically, we showed that mir-31 confers ddp-induced apoptosis and that inhibition of abcb9 is required for ddp resistance. 24099915_2 the data demonstrate that mir-31 exerts an anti-apoptotic effect most likely through the inhibition of abcb9 and thus provide a novel strategy involving the use of mir-31 as a potential target in nsclc chemotherapy 18449891_1 taken together, our findings suggest that mir-15b and mir-16 could play a role in the development of mdr in gastric cancer cells at least in part by modulation of apoptosis via targeting bcl2. 18978044_2 mentioned above, the sequences upstream of ompx, nade, and luxs that are capable of pairing with cyar overlap the ribosome binding sites of these genes, while the predicted pairing region of yqae is immediately downstream of its start codon. 25341039_1 taken together, our results suggest ctgf activates pi3k, akt, erk, and nf-kappab/elk1 pathway, leading to the upregulation of mir-210, contributing to inhibit gpd1l expression and prolyl hydroxylases 2 activity, promoting hif-1alpha-dependent vegf expression and angiogenesis in human synovial fibroblasts. 25341039_2 therefore, mir-210 directly represses gpd1l expression through binding to 3'-utr of human gpd1l gene. 25341039_3 we also indicated that mir-210 directly repressed gpd1l protein expression through binding to 3'-utr of human gpd1l gene, thereby negatively regulating gpd1l that is documented as promoting phd activity and later impeding hif-1alpha expression. 19014482_1 mir-146a expression was found to be directly stimulated by tax via nf-kb-mediated transactivation of its promoter; a single nf-kb site proximal to the transcription start point was necessary and sufficient for this to happen. 23886157_1 in comparison to the controls, a significant increase in the expression of mir-451 was associated with significantly decreased expression of cab39, lkb1, ampk, akt, pi3k and bcl2. 9770507_1 dsra enhances the translation of the stationary phase and major stress response sigma factor rpos. dsra base pairing to the inhibitory strand of the rpos translational operator prevents rpos intrastrand base pairing, freeing the shine cdalgarno sequence and enabling translation. 21403094_1 suggesting that sox6 and rod1 were target genes of mir-499. 26252024_1 in the present study, we found that mir-144 decreased the expression of pten and increased the expression of pakt in the mda-mb-231 and skbr3 cells. 25696812_3 4a, the overexpression of mir-9 inhibited the 3'-utr luciferase reporter activities of kpnb1 and dyrk1b by 37% and 67%, respectively, but had no effects on activities of dyrk2 and csnk1a1, indicating that kpnb1 and dyrk1b might be the targets of mir-9. 26388699_1 further, tumor protein 53-induced nuclear protein 1 was an important target of mir-125b involved in metastasis of nsclc cells. 26388699_2 further, tumor protein 53-induced nuclear protein 1 was identified as a critical target of mir-125b involved in nsclc metastasis. 26388699_3 these results suggested that tp53inp1 was a bona fide target of mir-125 in regulating the metastasis of human nsclc. 26154388_2 these 50 mrnas have highly coordinated biological interactions, centered around the apoptotic regulator and mir25 target, tumor protein 53 or tp53 . 26154388_3 inverse relationships between mirna and the 50 target mrnas were observed for protein arginine methyltransferase 5 and tp53 and ras-related c3 botulinum toxin substrate 1 , where the targets for each were downregulated, and the mirnas themselves upregulated in ar. the opposite was also found for caudal type homeobox 2, ataxia telangiectasia mutated, and homeodomain interacting protein kinase 2 ; mitotic arrest deficient-like 1, histamine receptor h1, lamin b2, and denticleless e3 ubiquitin protein ligase homolog ; tgf r1, tgf r2, sam pointed domain containing ets transcription factor, and snail family zinc finger 1 ; nuclear receptor corepressor 2 and activin a receptor, type iib . 20827281_1 the ednra and eya4 transcripts harbor two predicted targetsites for mir-27b and one site each for mirs-203 and -224. 20827281_2 gdap1 contains two sites for mir-203 and single sites for mirs-26a and -200a . 20827281_3 as shown in figure 2a, both mir-27b and mir-224 mediated significant repression of the ednra reporter, whereas mir-203 had only a mild effect. 20827281_4 the eya4 3'-utr was targeted by all three tested mirnas , and gdap1 was repressed by both mirs-26a and -200a, but not by mir-203 . 26703568_1 through a series of screening strategies and experimental validations, it was identified that hsa-mir-218 targets and represses the expression of alas2 by binding to the3 1 -untranslated region . 26703568_2 taken together, our results show that mir-218 inhibits erythroid differentiation and alters iron metabolism by targeting alas2 in k562 cells. 26703568_3 through a series of screening and functional studies, we found that mir-218 inhibited erythroid differentiation and altered iron metabolism by targeting alas2 in k562 cells. 26703568_4 these data revealed that alas2 expression is down-regulated by mir-218 binding. 26148972_1 finally, gad2 showed a significant increase in expression after transfection with mir-370 or -495 inhibitors . 22232084_1 nevertheless, our datasuggest a direct binding by mir-293 to multiple, low affinity sites within the cds of p65. 22232084_2 figure 2. p65 is targeted by mir-290 cluster. 22232084_3 these data define p65 as a novel target gene of mir-290 cluster. 22232084_4 overexpression of mir-291b and of mir-293 or of both mirnas together resulted in a significant reduction of p65 protein levels, whereas mrna levels almost remained unaffected . 21953056_1 mir-25 repressed dr4 protein levels via direct targeting of the 3'utr of dr4. 21953056_3 these findings confirmed that dr4 is a targetprotein for regulation of the trail-induced death pathway by mir-25. 21953056_4 therefore, our data are consistent with the hypothesis that mir-25 repressed dr4 protein levels via direct targeting of the 3'utr of dr4. in conclusion, overexpression of mir-25 in cholangiocarcinoma was observed to negatively regulate apoptosis signaling and dr4 protein levels. 18299402_3 we also observed repression of cebpb, pu.1, cutl1, and picalm protein levels in raw 264.7 cells expressing mir-155 , albeit to somewhat varying degrees between experiments .next, 17968323_1 a bioinformatics search revealed a conserved target-site for mir-21 within the pdcd4-3'-utr at 228-249 nt. in 10 colorectal cell lines, an inverse correlation of mir-21 and pdcd4-protein was observed. 17968323_2 transfection of colo206f-cells with mir-21 significantly suppressed a luciferase-reporter containing the pdcd4-3'-utr, whereas transfection of rko with anti-mir-21 increased activity of this construct. 17968323_7 this is the first study to show that pdcd4 is negatively regulated by mir-21. 24921914_1 mir-224 promotes the chemoresistance of human lung adenocarcinoma cells to cisplatin via regulating g /s transition and apoptosis by targeting p21 . 26722251_1 in addition, the present study demonstrated that unlike mir-339-5p, prl-1 expression was not regulated by mir- 339- 3p. the present authors previous study indicated that mir-339-5p inhibits crc cell proliferation and migration by regulation of prl-1 expression and the erk1/2 signaling pathway. 26722251_2 the present authors previous study previous studies demonstrated that the suppressive effects of mir-339-5p on crc cells may be partially due to its regulation of prl-1 expression and activation of the erk1/2 signaling pathway. 26474386_1 in order to determine whether mir-375 regulates klf5 directly we constructed vectors containing either the wild type 3'-utr or mutant 3'-utr of klf5 fused directly downstream of a the firefly luciferase gene .4a. the luciferase activity in cells co-transfected with the wild type vector and the mir-375 mimic was significantly reduced compared with the negative control , while the luciferase activity of the mutant 3'-utr was not significantly altered .4a. these results strongly suggest that mir-375 binds directly to the 3'-utr of klf5. 26474386_2 our results demonstrate that the mir-375 mimic significantly down-regulated klf5 expression in both cal27 and wsuhn6, while treatments with the mir-375 inhibitor increased klf5 levels. 22110210_3 the loss of mir-206 may play an important role in the progress of lscc and mir-206 may function as a novel tumor suppressed mirna. 25695396_3 our study showed that stoml-2 was negatively regulated by mir-1207-5p. 22870278_1 here we report that mdm4 mrna is a target of hsa-mir-34a . 22870278_2 over expression of mir-34a inhibits expression of known target and mdm4. 22870278_3 the mdm4 open reading frame contains a functional mir-34a site. 22870278_4 thus, the mir-34a site in the coding region of mdm4 exon 11 is functional and responsive to mir-34a. 22797699_1 a significant repression of the luciferase activity was observed for all 3'-utr reporters containing a perfect match target site, whereas there was no change in luciferase activity for the reporters harboring mutations in the mir-155 target site sequences, implying that mafb, shank2, and sh3pxd2a are indeed bona fide targets of mir-155 . 22797699_2 with the aim of understanding which of the aforementioned targets play a role in the pathogenesis of low-grade b-cell lymphomas, in the present study, we carried out gep in wm cells and found that 3 known mir-155 targets, smad5, socs1, and cebp-beta , as well as 3 novel mir-155 targets, mafb,shank2,and sh3pxd2a,were derepressed after anti-mir-155 treatment. 21703006_1 four target genes of mir-148a were identified to be up-regulated within its regulated pin, including pai-1 , itgb8 , vav2 and c . 20103675_1 we further validated the specific interaction between mir-222 and the putative binding site of ppp2r2a transcript in the presence of mir-222 inhibition. 20103675_4 we were able to further substantiate the negative regulatory role of mir-222 on ppp2r2a by assessing the protein level of ppp2r2a in hep3b and hkci-9. 20439489_1 on this basis, we first demonstrated that smarca5 is a direct target of mir-100, jarid1b of mir-137, and we also confirmed previously published data demonstrating that sirt1 is a direct target of mir-34a in a different context. 20439489_3 2a, we confirmed that overexpression of mir-34a induced a significant suppression of sirt1. 25738901_1 following ng treatment, the mrna and protein expression of pdcd4 in macrophages transfected with anti-mir-21 inhibitor was higher than in those transfected with negative control , which indicated that in macrophages, mir-21 inhibition promotes pdcd4 expression and that pdcd4 is the target gene of mir-21. 20444703_1 we demonstrate, using an mir-10b synthetic precursor, expression vector, andantisense oligonucleotide, that mir-10b represses tiam1 expression in breast carcinoma cells and that it interacts with the 3'-utr of tiam1. 20444703_2 ectopic expression of this mir-10b in sum159pt cells resulted in a significant decrease in tiam1 expression . 20444703_3 importantly, co-transfection of mir-10b and tiam1 cdna lacking the 3'-utr was able to rescue mir-10b-induced repression of cell motility , suggesting that tiam1 is a key factor responsible for decreased cell motility in cells expressing mir-10b. 26096363_1 both fluorescent quantitation and western blot analysis showed that mir-132 significantly inhibited the transcription and expression of yap , suggesting that mir-132 may be the mirna targeting yap gene 23818645_2 because bcl-6 is a negative regulator of t h 17 differentiation, we hypothesized that the mir-132/212 cluster participates in t h 17 differentiation by targeting bcl-6 . 23818645_3 this computational analysis demonstrated that mir-212, but not mir-132, potentially binds the bcl-6 3- utr . 23818645_4 the results of luciferase assays revealed that mir-212, but not mir-132, binds to the bcl-6 3- utr . 23936419_2 mir-34a was also up-regulated by genistein and may directly target hotair in both pc3 and du145 pca cells 12475232_2 tar rnas containing single nitroxide spin-labels in the 2'-position of u23, u25, u38, or u40 were incubated with compounds known to inhibit tar-tat complex formation. 25322930_1 therefore, mirna-135a-5p increased bcl-2 via ap-2alpha and consequently enhanced cell resistance to apoptosis. 26695142_2 the above results demonstrated that mir-137 downregulated egfr at both mrna and protein levels. 26695142_3 the above results indicated that mir-137 binds to the 3'-utr region of egfr directly. 26695142_4 in addition, reporter assays demonstrated that mir-137 was bound to the egfr 3'-utr directly, indicating that egfr is the direct target of mir-137. 21315047_1 theses results suggested that mir-196a regulates the expression of hoxa9 by targeting the complementary sites. 22350414_1 we identified casein kinase 1alpha as a direct target of mir-155 control which enhanced beta-catenin signaling and cyclin d1 expression, promoting tumor cell growth. 22350414_2 these results suggested that ck1alpha is a direct mir-155 target. 22350414_3 taken together, our data identified ck1alpha as a novel mir-155 target and suggested that mir-155 overexpression enhances the activation of -beta-catenin in these malignancies. 26468775_1 this result suggests the significant importance of simultaneous suppression of axin2, dkk3 and sfrp1 by mir-582-3p. 26468775_2 mir-582-3p simultaneously targets axin2, dkk3 and sfrp1 26575121_1 moreover, luciferase reporter gene assays showed that smad7 was a validated mir-21 target, cell transfection showed that mir-21 overexpression downregulated target smad7 expression. 26575121_2 taken together, our data exhibited that mir-21 was involved in renal injury of dn by directly down-regulating smad7, and that smad7 was a validated mir-21 target. 26090403_1 to study whether meg3 levels are associated with vegf expression, pearson correlation coefficient was calculated as a measure of the degree of linear dependence between vegf and meg3 in the oa group. 26090403_2 pearson's r '~0.53409 with p ' 0.0153, which indicates there is significant negative correlation between vegf and meg3 given a significance level of alpha ' 0.05. 21468029_1 figure 5 mir-214 downregulates tfap2c and itga3 target genes and modulates multiple surface proteins. 21468029_2 these data suggest that the mir-214-dependent regulation of met and itga3 is at least in part mediated by tfap2c. 22326282_1 we could confirm the already known regulation of the apoptosis inhibitor api5 by mir-224 and could further identify three novel mir-224 target genes . 22248719_1 mir-376b controls starvation and mtor inhibition-related autophagy by targeting atg4c and becn1. 21368870_2 to determine whether irf1 is a true target of mir-383, nt2 cells were transfected with mir-383 mimic/control or mir-383 inhibitor/control. 21368870_3 both irf1 protein and irf1 mrna expressions were significantly decreased in mir-383-transfected nt2 cells than in control cells, whereas knockdown of mir-383 increased irf1 protein expression. 21368870_4 to further validate the regulatory relationship between mir-383 and its targetirf1 in vivo, expressions of mir-383 and irf1 protein were identified in the normal human/mouse testis and in human infertile testis. 21368870_5 taken together, these results demonstrate that mir-383 downregulates irf1 directly by decreasing mrna stability. 21368870_6 these observations corroborate the negative correlation between the expression of mir-383 and irf1 in ma patients. 23888996_3 these results provide a possible underlying molecular mechanism to explain the association between reduced mir335 with poor clinical outcome, and suggest that approaches to re-introduce mir335 expression or override mapk1 activity may offer promising therapeutic strategies in the treatment of all. 22388101_2 mir-409-3p may function as a novel tumor suppressor in gc and its anti-oncogenic activity may involve the direct targeting and inhibition of phf10 20054641_1 human mir-128a was shown to negatively target tgf-betari protein expression by binding to the 3'utr region of the gene. in addition, though mir-128a did decrease protein levels of tgf-betar1, the mrna levels of tgf-betar1 remained unchanged , as the binding site of mir-128a to the 3'-utr of tgf-betar1 gene is an imperfect match. 20054641_2 these results further confirm the role of mir-128a in regulating tgf-betar1 expression, a process which is mediated by a target binding sequence within the 3'-utr of tgf-betar1. 20054641_3 human mir-128a post-transcriptionally targeted tgf-betar1. 20054641_4 as a functional consequence of this antagonism, the question was asked whether inhibiting mir-128a would then sensitize the t+let r cells to the growth inhibitory effect of tgf-beta1. 25429623_1 analysis of transcript levels by rt-qpcr revealed that mir-23a levels decreased in heat-stressed cells and that this was correlated with an increased abundance of noxa mrna, which contains a mir-23a binding site in its 3' untranslated region. 22689670_1 mir-125b controls apoptosis by down-regulating genes involved in the p53 pathway including bak1 and tp53inp1. 22689670_2 as shown in figure 4d, bak1 and tp53inp1 were down-regulated by mir-125b over-expression in all three cell lines. 22689670_3 we demonstrated that abtb1, an anti-proliferative factor, is a new direct target of mir-125b, and showed that in these lines mir-125b also down-regulates a series of targets previously identified in other cell types or species, including cbfb, a transcription factor involved in hematopoiesis, as well as other genes upstream or downstream of p53 including bak1, tp53inp1, plk3, ppp1ca, prkra and ppp2ca. 26152689_2 methylation-associated mir-9 down-regulation is probably one of the key mechanisms for paclitaxel resistance in eoc cells, via targeting ccng1. 26152689_3 these data validate that mir-9 can directly bind to 3- utr of ccng1 and ccng1 is regulated by mir-9. 26361139_1 in this study, we showed that mir-378 can target tailless , a critical regulator of nsc, to regulate nsc proliferation and differentiation. 26361139_2 taken together, our data suggest that mir-378 is a novel mirna that regulates nsc proliferation and differentiation via targeting tlx. in this study, we demonstrated that mir-378 could target and regulate tlx expression and thus participated in regulating nsc proliferation and differentiation. 25712342_1 functional analyses in vitro and in vivo revealed that foxp3-induced mir-146a/b negatively regulate nf-κb activation by inhibiting the expression of irak1 and traf6. 22419847_2 met proto-oncogene was identified as a target of mir-34b/c in uveal melanoma cells. 26897284_1 we demonstrated that mir-497 targets the mek1 3'-utr using three target scan algorithms targetscan, miranda and mirdb, and mir-497 suppressed mek1 expression in hela cells. 26896688_1 over-expression or down-regulation of mir-451a regulated expression of 14-3-3味 and eralpha 23342366_1 ebv-encoded bart mirnas target the 3'-utrs of viral genes, such as lmp1, balf5, and lmp2a genes, and negatively regulate expression of these viral genes.on the other hand, ebv mirnas repress cellular proteins, which include p53 up-regulated modulator of apoptosis , dicer1, and bim. 26078955_1 taken together, our data indicated that mcl-1 3'-utr is the direct target of mir-26b and suggested that mir-26b could suppress the expression of mcl-1. 26078955_2 mcl-1 mrna 3'-utr is the direct target of mir-26b. 26078955_4 predicted binding site of mir-26b in 3'-utr of human mcl-1 mrna. 22932723_1 furthermore, it was shown that pdgf-b was a targetfor mir-29b as evidenced by the fact that binding of mir-29 to the 3'-untranslated region of pdgf-b mrna resulted in its translational repression in sh-sy5y cells. 22932723_2 mir-29b target pdgf-b 3'-utr resulting in translational suppression. 22932723_3 taken together, these findings implicate that tat- and morphine-stimulated astrocytes release exosomes containing mir-29b, which can be taken up by neighboring neurons, resulting in downregulation of the expression of the targetgene - pdgf-b. 22932723_4 these results thus underpin the role of mir-29b in regulating pdgf-b protein expression via a posttranscriptional mechanism. 19096009_1 these results indicated the requirement for e2f1 and myc for the deacetylase-induced transcriptional induction of mir106b. 19096009_2 more importantly, there was a strict positive correlation between expression of e2f1 and up-regulation of mcm7-mir106b, indicating that e2f1 probably positively regulates mir106b expression in response to lbh589 in primary cll cells. 23784775_1 we also showthat ubash3b is a functional target of anti-invasive microrna200a that is down-regulated in tnbc. 23784775_2 we show that ubash3b acts as a crucial downstream target of invasive regulator mir200a, and that its oncogenic function requires phosphatase activity. 23784775_4 we have shown that ubash3b is a direct and functional target of mir200a, and thus up-regulation of ubash3b could be a result of mir200a down-regulation, as seen in tnbc. 21159887_1 interestingly, mir-203 repressed the protein levels of e-box-binding transcription factor zeb2, also known as smad-interacting protein 1 , a transcriptional repressor that regulates the expression of e-cadherin and emt . 21159887_2 also, mir-203 inhibited the expression of polycomb repressor, bmi1. 21159887_3 importantly, ectopic mir-203 repressed the expression of bone-specific transcriptional regulators, runx2 and dlx5, that are involved in homing of pca cells to bone. in addition, we found that smad4, a central mediator of tgf--beta intracellular signaling, is regulated by mir-203. 21159887_4 also, mir-203 repressed endogenous levels of transcription factor e2f1, which has been reported to be elevated in metastatic hormone-resistant pca . in agreement with the inhibitory effects of mir-203 on migration and invasion, we found decreased mmp10 expression in cells overexpressing mir-203. 21159887_5 we cloned the 3- - utrs of the targets that are potential mediators of the effects of mir-203 on pca progression and metastasis, namely, zeb2, runx2, dlx5, and smad4 into a luciferase construct. 21159887_7 it has been proposed that metastatic pca cells must be osteomimetic to metastasize, grow, and survive in the skeleton . in view of our present evidence suggesting the specific attenuation of mir-203 in bone metastatic pca cell lines and clinical specimens and the potential regulation of runx2 and dlx5, we asked if alteration of mir-203 levels affects the osteomimetic properties of pca cells. 25485975_1 ifg2 mrna translation in rat myoblasts is under positive control by mir-206, they are entirely consistent with this possibility and seem to constitute a provocative case. 22062548_1 to confirm the predicted targetsite in the eif5 3'-utr, we mutated the binding site that was hypothesized to interact with the seed region of mir-5787 . 22062548_3 therefore, we showed that mir-5787 directly repressed the eif5 transcript. 22062548_4 this result indicates that mir-5787 post-transcriptionally regulates eif5 expression. 26850657_1 dual luciferase assays in dgcr8d/dtbx21 cd4+t cells demonstrated that ccnk and aff4 are direct targets of mir-27, and cnot6 and clcn3 are direct targets of mir-24 in primary t cells . 26850657_2 the remaining three genes, ikzf1, gpr174, and galnt3, appear to be direct targets of both mir-24 and mir-27 . 22761427_1 thus, these results showed that two keratinization-associated mirnas, mir-7 and mir-21, could be important for regulating the expression of reck. 22761427_2 together, these data demonstrated that reck could be directly coregulated by mir-7 and mir-21 and that different endogenous levels of these mirnas in cells could contribute to the down-regulation of reck transcript. 21177782_1 mage-a2, mage-a3, mage-a6, and mage-a12 3'utrs are direct target for mir-34a. 21177782_4 to confirm that the increase in p53 and p21 transcripts in the presence of mir-34a was indeed mediated through the direct suppression of mage-a genes, we cloned the mage-a2, mage-a3, mage-a6, and mage-a12 full-length coding sequences bereft of the 3'utr, thus rendering these transcripts impervious to targeting by mir-34a. 25561284_1 to understand the mechanism of the mir-491-regulated hcc cell proliferation and cell survival, we tried to identify mir-491 target genes and found that egfr is a putative target of mir-491. 25561284_2 to validate egfr is a direct target of mir-491, we constructed luc-egfr-3' utr-wild-type and its 30 utr mutant plasmids. 25394756_1 the proliferation of gscs cell could be inhibited with high-expression of mir-21 and this effect could be restored by mir-21 knocked down. 25394756_2 mechanism analysis revealed that faslg was a specific and direct target gene of mir-21. 25394756_3 the advanced effects of anti-mir-21 on gscs apoptosis and proliferation were mediated by expression of silenced faslg. 22350415_1 notably, mir-130a inhibited autophagy by reducing autophagosome formation, an effect mediated by downregulation of the genes atg2b and dicer1, the latter of which is a major component of the mirna silencing machinery. 26482503_1 mir-125b regulates pct expression through targeting stat3 25299770_1 mir-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both bcl-xl and egfr leading to bim activation. 21289630_1 furthermore, we found that mir-141 directly targeted the 3'-untranslated region of yap1, which is known to have a crucial role in apoptosis induced by dna-damaging agents, and thus downregulated yap1 expression. 25239093_1 in silico database analysis result revealed that plk2 is a potential target of mir-27a. 25239093_3 mir-27a and knockdown of plk2 caused the increase of the cell viability and colony formation and inhibition of the late apoptosis in the hep2 cell lines. 20570349_1 transfection of precursor molecules of mir-196a and mir-196b induced erg downregulation and luciferase assays confirmed binding of mir-196a and mir-196b to the erg 3'utr. 20570349_2 moreover, analysis of the expression regulation of the specific isoforms revealed a downregulation of erg3 expression levels by mir-196a and mir-196b in kg1a . 20570349_3 the results show that erg expression is directly regulated by mir-196a and mir-196b. 20947512_3 consistent with the western blot results, both mir-9 and mir-30 led to a reduction of endogenous lin28 in es cells. in summary, during es cell differentiation and eb formation, the expression level of lin28 decreases, whereas its regulatory mirnas display an inversely correlated expression pattern. 18977327_4 growth factor-induced mir-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate mrna, leading to decreased levels of hgs and thereby reducing hgs-mediated degradation of the growth factor receptors vegfr2 and pdgfrbeta. 21248104_1 in a superimposed image of adjacent sections of mir-9, detected by in situ hybridization, and foxp1, detected by immunohistochemistry, mir-9expression overlapped with most foxp1-expressing mns . 21248104_2 because mirnas usually silence target gene expression, the overlapping expressions of mir-9, foxp1, and isl1/2 in lmc mns lead us to examine whether mir-9 may negatively regulate foxp1 and/or isl1/2 expressions . 21248104_3 because mirnas function by silencing target mrnas, the reduction in foxp1+ and isl1/2+ neurons suggests that mir-9 may directly or indirectly repress foxp1 and isl1/2 proteins . 21248104_4 bioinformatic approaches predicted foxp1 as a target of mir-9, which is consistent with the reduced foxp1 levels when mir-9 was overexpressed . 21248104_5 we first compared expression patterns of mir-9 with foxp1 mrna and protein in developing chick spinal cords. 21248104_6 at stages 11 and 17, mir-9 and foxp1 were detected in the vz. 21248104_7 expression of mir-9 overlapped with foxp1 mrna and protein in mns by stage 20 and was increased by stage 24 . 21248104_8 at stage 29, whereas foxp1 expression was maintained in lmc mns, mir-9 expression was greatly reduced . 21248104_9 these studies suggest that mir-9 expression coordinates with foxp1 in lmc mns during the critical time of mn columnar formation. 21248104_10 the overlapping expression of mir-9 and foxp1 and the repressing function of mir-9 on foxp1 suggest that mir-9 controls foxp1 levels in the lmc mns with a tuning regulation. 21248104_11 both mir-9-1 and mir-9-2, but not mir-9-mut and control mir-17, significantly decreased luciferase activities, which confirmed the direct targeting effect of mir-9 on foxp1 3'-utr site 1 sequences . 22450659_1 in the present study, we report that mir-124 down-regulated sphk1 expression by directly targeting its 3'-untranslated region and that mir-124 expression was inversely correlated with sphk1 expression in gastric cancer samples. 22450659_2 mir-124 inhibits cell proliferation in gastric cancer through down-regulation of sphk1. 22450659_3 taken together, our results suggest that down-regulation of mir-124 in gastric cancer results in sphk1 over-expression. 22450659_4 taken together, our results suggest that sphk1 has an important role in the mir-124-mediated proliferation inhibition. 22450659_5 notably, re-expression of sphk1 in mir-124 over-expressed gastric cancer cells reversed the effects of mir-124, suggesting an antiproliferative role of mir-124 attributable largely to down-regulation of sphk1. 25606826_1 further investigation identified ras related protein rab5a as a direct target of mir-101. 26655604_1 mechanistically, phosphatidyl inositol 3-kinase interacting protein 1 , a negative regulator of pi3k, was identified as a novel target of mir-let-7 by a crosslinking technique showing that mir-let-7g specifically targets pik3ip1 to the cardiac myocyte argonaute complex risc. 26655604_2 mechanistically, we identify a novel target of mir-let-7g, pik3ip1, that acts as an inhibitor of akt survival signaling and whose levels increase with loss of mir-let-7 both in mouse models and in human myocardium. 26655604_3 the wild type 3'-utr of pik3ip1 was also functionally targeted by mir-let-7g but not nt sequence . 20404348_1 in consensus, overexpression of mir-21 in a transgenic mouse heart resulted in suppression of ischemia-induced up-regulation of pten and fasl expression, an increase in phospho-akt, a smaller infarct size, and ameliorated heart failure. 20404348_2 pten is a validated mir-21 target . 20404348_3 this suggests that mir-21 directly targets and inhibits fasl. 20404348_5 this suggests that caakt suppresses fasl and pten during hypoxia through an mir-21-dependent mechanism. 21199010_2 mir-99a, mir-125b, mir-216a and mir-1296 were putative negative regulators of rasgrp3, gpr160, prkch and xaf1, respectively, which were found to be differentially expressed in lcls during long-term culture in a previous study. 21199010_3 linear regression analysis showed that mir-200a and mir-296-3p correlated with triglyceride and hba1c levels. 17622355_1 the up-regulation of mir-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of mir-203, suppressor of cytokine signaling 3 , which is involved in inflammatory responses and keratinocyte functions. 17622355_2 next, we analyzed the expression pattern of mir-203 and socs-3 in lesional skin of psoriasis patients and in healthy skin . in situ hybridization using lna-modified nucleotide probes revealed that mir-203 is expressed in the suprabasal layers of the epidermis in normal skin, confirming its keratinocyte-specific expression observed in vitro . in comparison to healthy skin, the expression of mir-203 was increased in psoriatic lesional skin in all epidermal layers , consistent with the real-time pcr results. 17622355_3 analysis of socs-3 protein expression by immunohistochemistry showed a complementary pattern with the mir-203 expression . 17622355_4 thus, the up-regulation of mir-203 may have important implications for psoriasis pathogenesis by preventing the up-regulation of socs-3 in response to cytokines. 26452132_1 mechanistically, mir-7 targets raf-1 proto-oncogene serine/threonine kinase and mechanistic target of rapamycin . 26452132_2 co-transfection with mir-7 suppressed luciferase activity of both the raf1 and egfr reporters when compared with that co-transfected with mir-nc, confirming the seed binding sequences of mir-7 on the 3'utr region of raf1 and egfr genes. 26452132_3 mir-7 achieves this by directly targeting the mapk and mtor signalling pathways , leading to inhibition of cdk1. 26452132_4 taken together, these results indicate mir-7 acts as a tumor suppressor in acc by affecting multiple molecular targets, involved in the mtor and mapk signalling pathways. 18327259_1 the mir-17-92 mirna suppressed expression of the tumor suppressor pten and the proapoptotic protein bim. 25785039_1 confirmed by dual-luciferase assay and western blot, we found that mir-19a suppressed adrb1 expression by directly targeting 3'-utr. in conclusion, this study confirmed mir-19a suppressed adrb1 expression by directly targeting 3'-utr of adrb1 and found an positive correlation between plasma mir-19a and bnp or camp levels in hf patients, which may contributes to fully understand the hf pathogenesis and develops new therapy for hf. 26022123_1 moreover, a change in mrna and protein expression levels of zeb1 and zeb2 in response to mir-139-5p over-expression or inhibition was verified by rt-pcr and western blotting in hep3b and smmc7721 cells , confirming that mir-139-5p negatively regulates zeb1 and zeb2 expression by directly targeting their 3' utr regions. 26022123_2 these results confirm that zeb1 and zeb2 are regulated by mir-139-5p and mir-139-5p down-regulation, and may participate in hcc carcinogenesis and progression through potentiation of zeb1 and zeb2 expression. 22265968_1 lkb1 messenger rna was identified as a target of mir-199a-3p, and its expression was reduced in human fibrotic liver tissue. 22265968_2 the pairing between lkb1 3'-utr region and mir-199a-3p sequence was nearly perfect , which suggested that lkb1 mrna might be a target of mir-199a-3p. 22265968_3 to precisely define the inhibitory role of mir-199a-3p for lkb1, in vitro functional assays were performed by enhancing or silencing mir-199a-3p. 22265968_4 as expected, transfection with pre-mir-199a-3p significantly decreased the level of lkb1 protein . 22265968_5 figure 3 lkb1 mrna as a target of mir-199a-3p. 26506418_1 zfas1 is predicted to sponge mir-590-3p targeting cyclin-dependent kinase 1. 26036638_2 mir-101 sensitizes tnbc cells to paclitaxel-induced apoptosis by targeting mcl-1. 26537990_1 luciferase activity assay confirmed that wnt1 and wnt5a were both the target genes of mir-146a-5p. 26537990_2 in conclusion, mir-146a-5p suppresses activation and proliferation of hscs in the progress of nonalcoholic fibrosing steatohepatitis through targeting wnt1 and wnt5a and consequent effectors alpha-sma and col-1. 26537990_3 these results suggest that mir-146a-5p regulated wnt1 and wnt5a genes expression at the posttranscriptional level. 26655273_2 we further confirmed that igf-1r was a target of mir-122. 26655273_3 these data indicate that mir-122 negatively regulates igf-1r expression by interacting with its 3'-utr. . 26655273_4 together, these data suggest that igf-1r is a functional target of mir-122. 26655273_5 based on bioinformatics analysis and our experimental data, igf-1r is a functional target of mir-122 in hcc cells. 19487573_1 as a side note, we were also able to confirm in glioblastoma cells the mir-26a-mediated knockdown of ezh2 and smad1, both of which are known target of the mirna . 20375304_1 furthermore, mir-146a transduced cells showed diminished expression of the mir-146a target traf6 . 20375304_2 based on this finding together with the fact that mir-146a target traf6 and irak1, it was proposed that mir-146a is involved in a negative-regulatory feedback loop securing monocyte deactivation after stimulation . 25712478_1 in sum, both mir-99a and mir-150 bear the potential to repress mtor, a critical driver of th17 cell differentiation. 25712478_2 results obtained from mutating the mir-150 target site in the mtor 3' utr provided unambiguous proof that mtor is a direct target of mir-150 repression . 25712478_3 the result demonstrated downregulation of the mtor protein level as a consequence of mir-99a expression. 26912204_1 the luciferase assay results showed that overexpression of mir-125a significantly decreased the luciferase activity of the wild-type bmf 3- utr reporter; however, the two binding sites in the mutated reporter vector did not respond to the increased level of mir-125a . 24706111_1 the expression of mir-218 is down-regulated in an imatinib mesylate-resistant gist cell line , whereas mir-218 over-expression can improve the sensitivity of gist cells to imatinib mesylate, with pi3k/akt signaling pathway possibly involved in the mechanism. 24378652_2 in addition, we identified insulin-like growth factor-1 receptor mrna is a bona fide target of mir-503 by computational analysis followed by luciferase reporter assays. of note, upregulation of mir-503 in gbm cells suppressed endogenous igf-1r protein expression. 24378652_3 further mechanistic analysis revealed that forced expression of mir-503 inhibited akt activation, suggesting the tumor suppressive effect of mir-503 in gbm cells is partially mediated by phosphatidylinositol 3-kinase/akt signaling. 23142218_1 a reporter assay with the 3'utr of st7l cloned downstream of a luciferase gene showed increased luciferase activity in the absence of mir-24, providing strong evidence that mir-24 is a direct regulator of st7l. 23142218_2 st7l protein expression was also significantly up-regulated in u87 and ln229 cells that were transfected with the mir-24 inhibitor, indicating that st7l is a direct target of mir-24. 23142218_3 these results suggest that mir-24 represses st7l expression through the predicted targeting sites in the st7l 3' utr. 23142218_4 these results suggest that the carcinogenesis effects of mir-24 are in part facilitated by st7l downregulation. 23142218_5 taken together, these data suggest that mir-24 regulates b-catenin/tcf-4 transcriptional activities via st7l, at least in u87 and ln229 cells. 22847819_1 molecular analyses of the transgenic mice showed decreased expression of the major target gene termed mitf. 22847819_2 mir-137 targets mitf directly in primary mice melanocyte cell line. 22847819_3 considering that mir-137 was recently reported to down-regulate mitf in melanoma cell lines. 22847819_4 bioinformatic analysis showing mir-137 target binding sites in 3- utr of mitf. 22847819_5 mitf protein levels were significantly reduced by 0.5-fold below the control group , suggesting a strong translational repression of mitf was induced by the overexpressed mir-137. 26459797_1 luciferase assay revealed that mir-33b bound to zeb1 3'-utr region and inhibited zeb1 expression, while expression of zeb1 mrna and mir-33b was inversely associated with lung adenocarcinoma cell lines and tissues. 26459797_2 taken altogether, our data indicate that mir-33b targets zeb1 expression by binding to zeb1 3'-utr region to modulate proliferation, migration and invasion of lung adenocarcinoma cells. 26459797_3 indeed, our current data showed that: i the expression of mir-33b and zeb1 was inversely correlated in lung adenocarcinoma cells and tissues; ii mir-33b bound to zeb1 3'-utr region; 18319255_1 mir-224, which is up-regulated in the tumors of hcc patients, sensitizes cells to apoptosis through/r/nthe inhibition of api-5 at the mrna levels and increases cell proliferation. 18319255_2 significantly, mir-224 expression was found to be inversely correlated with api-5 expression in hcc patients. 19435871_2 low or absent mir-200c results in aberrant expression of zeb1 and consequent repression of e-cadherin. 19435871_3 reinstatement of mir-200c to such cells restores e-cadherin and dramatically reduces migration and invasion. 19435871_4 microarray profiling reveals that in addition to zeb1 and zeb2, other mesenchymal genes , which are also predicted direct targets of mir-200c, are indeed inhibited by addition of exogenous mir-200c. 19435871_5 one such gene, class iii beta-tubulin , which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of mir-200c. 19435871_7 because expression of tubb3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of mir-200c to restore chemosensitivity to such agents may be explained by its ability to reduce tubb3. 23108995_1 as expected, this suppression was abolished by deleting part of the perfectly complementary sequences in the rb1 3' utr which disrupts the interaction between mir-26a and rb1 . 23108995_2 further, we identified that rb1 is the direct functional target of mir-26a, and revealed that the reduction of mir-26a expression leads to increased rb1 protein level and thus inhibits the function of e2f1, by which it influences the phenotypes of cell cycle and anoikis. 23108995_3 rb1 is a direct functional target of mir-26a in ea cells. 19767219_3 mirna-221 silencing predisposed t24 cells to undergo apoptosis induced by trail and resulted in an up-modulation of cyclin-dependent kinase inhibitor p27kip1. 19767219_4 mirna-221 suppression promoted the activation of caspase 3 induced by trail in t24 cells. 23337879_1 these results demonstrate that mir-214 can binddirectly to the bcl2l2 3'utr to repress gene expression. 23337879_2 together, our data provide the evidence that mir-214 may induce apoptotic signals at least in part through regulation of the amount of bcl2l2. 23337879_3 together, these data suggest that bcl2l2 is indeed a direct targetgene of mir-214. 23337879_6 2c and d, bcl2l2 mrna and protein levels were both inhibited in hela/mir-214 cells, indicating mir-214 can negatively regulate the expression of bcl2l2 at the post-transcriptional level. 21081489_1 ets-1 is a novel target of mir-200b. 21081489_2 mir-200b is involved in induction of angiogenesis via directly targeting ets-1 in hmecs. 21081489_3 as expected, deletion of the ets-1 3'-utr sequence from the construct abolished the inhibitory effects of mir-200b on luciferase activity . 21081489_4 these results establish that mir-200b interact with the ets-1 3'-utr to exert translational repression. 22850877_1 reporter assays were carried out to determine whether mir-34a binds directly to these 3'-utrs as well as those of other predicted mir-34a target genes identified in our analysis that are not directly involved in rho gtpase regulation, but are potentially important in tumorigenesis . 22850877_2 arhgap1 reconstitution repressed basal gtp-bound cdc42 and rescued tgf--beta-搃nduced sphere invasion in matrigel , which suggests that mir-34a represses tgf--beta-搃nduced tumor cell invasion by downregulating arhgap1. 25174799_1 microrna-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor ifit2. 25351256_1 to verify whether p27kip1 is a direct target of mir-429, a dual-luciferase reporter system using pmir-report鈩 luciferase vectors containing wt or mutant p27kip1 3'-utr was employed . 25351256_3 transfection with mir-429 mimics significantly reduced the endogenous p27kip1 mrna and protein expression levels in if11 and ia8 cells . in conclusion, these data suggest that p27kip1 is a direct target gene of mir-429. 26676658_1 upregulation of mir-215 notably inhibited the expression of xiap. in conclusion, we identified mir-215 as a potential tumor suppressor in patients with eoc downregulating expression of the oncogenic regulator xiap. 21970405_1 as shown in figure figure5e,5e, mir-125b significantly decreased the relative luciferase activity of wild-type tp53inp1 3'utr , whereas the reduction of the luciferase activity with mutant tp53inp1 3'utr was not as sharp as that observed in the wild-type counterpart, suggesting that mir-125b could directly bind to the 3'utr of tp53inp1. 21970405_2 taken together, these findings indicate that tp53inp1 is a direct downstream target for mir-125b in ec cells. 26443314_1 the mir-210 mimic effectively reduced rod1 expression as detected by western blot analysis, whereas the mir-210 inhibitor led to an increase in rod1 expression . . 26443314_2 this data indicates that rod1 is probably a target of mir-210 in gbm cells. 21095586_1 to assess the precise contribution of each mirna-binding site, we mutated the predicted mir-35-42 and bantam-binding sites within the toh-1, and egl-1 3'-utrs and examined their effects on deadenylation, and translation repression assays . 21095586_2 for reporters containing thetoh-1 3'-utr , mutating either the mir-35-42 or the bantam site alone effectively impaired deadenylation , wereas no deadenylation could be detected when using the double mutant 3'-utr . 21095586_3 while these data cannot rule out a weak and residual activity for the mir-35-42 site on its own, they indicate that the mir-35-42 and the cebantam mirna families cooperate synergistically in promoting the deadenylation and silencing on the toh-1 3'-utr. in similar reporter assays, the 3'-utr of the egl-1 mrna also mediated a potent translation repression, and a rapid deadenylation . 21095586_4 mutation of the mir-35-42 binding site on its own, or in combination with an additional mutation in the predicted bantam site at position 86, completely abrogated reporter deadenylation and translation repression . 26902120_1 taken together, these results suggested that mir-130b regulates os cell proliferation and apoptosis by directly targeting nkd2. 26472353_1 mir-145 directly targeted trim2 to derepress pro-apoptotic bim expression. 26472353_2 the interaction between mir-145 and 3'-utr of trim2 was specific. 20488920_2 after treatment of panc1 and l3.6pl cells with cddo-me, there was a decrease in expression of mir-27a , and this was accompanied by increased zbtb10 mrna levels . 20488920_3 this demonstrates that cddo-me-induced ros is a common upstream factor regulating disruption of mir-27a:zbtb10-揝p axis. 19502795_1 we focused on human -mir-124a that has a predicted binding site in the 3'utr of the ikappab mrna. 19502795_2 based on these structural features it is likely that ikappab is targeted by mir-124a. 19502795_3 although detailed functional studies are required to investigate these possibilities, our results suggest that mir-124a-controlled downregulation of ikappab is involved in the regulation of nfkappa activity. 24444604_1 mir-455 is negatively regulated in mir-155-deficient cells possibly due to inhibition of the transcription factor c/ebpbeta by mir-155. 17575136_1 the authors conclude that, in addition to mir-106a, mir-20b, mir-19b-2, and mir-92-2 overexpression in tumors, their capacity to induce anchorage independence growth strongly supports an oncogenicpotential for those mirnas. 17575136_2 they also conclude that mylip and rbp1-like are true targets of the mir-106-363 cluster . 17575136_3 more specifically, rbp1-like seemed only targeted by mir-106a/mir-20b, whereas mylip could be targeted by the four mirnas with mir-106a/mir-20b being more efficient. 25032870_1 mef2c is a direct target gene of mir-203 that has a positive role in myoblast differentiation. 25032870_2 the protein expression of mef2c was down-regulated during e14 and e16 , and it was upregulated from proliferation to differentiation of myoblasts , demonstrating that mef2c expression correlated with mir-203 levels in vitro and in vivo. 25032870_3 thus, mef2c is a target of mir-203, and its knockdown significantly represses the late stage of myoblast differentiation. 25032870_4 mef2c, a new target of mir-203 found in this study, is upregulated during c2c12 differentiation, 53 and its interaction with maml1, notch3 and the p38 mapk pathway is required for normal myogenesis . 26598317_2 six genes were significantly down-regulated in mir-17-92 mimics-transfected cells and up-regulated in mir-17-92 inhibitors-transfected cells. 26155421_2 qpcr analyses and immunohistochemical staining revealed an inverse expression of mir-148a and -133a with the hla-g protein in situ and in vitro. 26155421_3 recent studies demonstrated a strong post-transcriptional gene regulation of the hla-g by mir-152, -148a, -148b and -133a. 24710569_1 in the luciferase-based assay, we showed that the mir15a/16 lost their ability to bind to foxp3 when binding sites 1 and 2 are mutated . 24710569_2 annotation of the foxp3 3'-utr showing predicted binding sites of mir15a and mir16, their seed sequences and subsequent introduced mutations. 18193036_1 mir-373 and mir-520c stimulated cancer cell migration and invasion in vitro and in vivo. 18193036_2 mechanistically, the migration phenotype of mir-373 and mir-520c can be explained by suppression of cd44. 18193036_3 we found significant upregulation of mir-373 in clinical breast cancer metastasis samples that correlated inversely with cd44 expression. 26733177_2 these results suggest that the mechanism by which mir-145 promotes tnf-alpha-induced apoptosis is dependent on the downregulation of ciap1 in tnbc cells. 26733177_3 collectively, our study found that mir-145-induced ciap1 degradation facilitated tnf-alpha-induced apoptosis in tnbc. 21482222_1 in this study, we demonstrated that microrna-142-3p acted as a negative regulator of human rac1. 21482222_3 furthermore, to determine if mir-142-3p suppressed endogenous rac1 through translational repression, rac1 protein levels were detected by western blot analysis. 21482222_4 in qgy-7703 cells transfected with pcdna3/pri-mir-142-3p, the mature mir-142-3p level was significantly increased , and the rac1 mrna and protein levels were significantly reduced . 21482222_5 these data suggested that mir-142-3p negatively regulates endogenous rac1 protein expression through mrna degradation and translational repression. 21482222_6 thus, these results further supported that mir-142-3p negatively regulates rac1. 20577206_1 within the high homology region, we found perfectly conserved seed matches for the pten-targeting mir-17, mir-21, mir-214, mir-19 and mir-26 families . 20577206_2 to measure the role of these micrornas on both pten and ptenp1 expression, we designed specific pcr primer sets in the non-homologous 3'藟utr regions . in du145 prostate cancer cells, pten-targeting micrornas mir-19b and mir-20a suppress both pten and ptenp1 mrna abundance . in these cells, a pool of inhibitors of endogenously expressed pten-targeting micrornas de-repressed both pten and ptenp1 transcript levels . 20042474_1 ago protein was knocked down by mir-107 and mir-128. 19830559_1 we demonstrated that mir-141 levels correlate inversely with sip1 protein levels as well as cell migration and invasion of crc cells. 19830559_2 sip1 was identified as a functional target of mir-141. 19830559_3 conclusions: mir-141 regulates sip1 to inhibit migration and invasion of crc cells. 19830559_4 mir-141 and sip1 might be candidate therapeutic targets in crc. 25118937_1 we further show that mir-940 directly binds to the 3'-untranslated regions of nestin mrna and promotes its degradation. 25118937_3 these functions of mir-940 can be reversed by ectopic expression of nestin, suggesting that mir-940 regulates cell proliferation and survival through nestin. 22159356_1 we further demonstrate that mirna-205 can specifically suppress expression of vegf-a by directly interacting with the putative mirna-205 binding site at the 3'-utr. 22159356_2 herein, we found that the expression of vegf-a was significantly elevated with the ascending order of glioma grade , accompanying the decrease of mirna-205 . 22159356_3 these results indicate that mirna-205 directly modulate vegf-a expression by binding 3'-utr of vegf-a in glioma cells. 26426440_3 similarly, expression of hox9, spx and ta.42302 gradually increased from 14 to 28 dpa , accompanied by down-regulation of mir166, mir827 and ta-mirn8 expression . 26426440_6 by comparing the expression of mir164 and its validated targets, nac and psk1 , we found that the negative correlation with mir164 was more evident for psk1 than nac , inferring that psk1 might be a major target of mir164 in grain development. 21205300_1 using a luciferase reporter assay and western blot, cckbr was identified as a target of mir-148b in cells. 21205300_3 these results indicate that cckbr may be a target of mir-148b. 21205300_5 despite the effect of mir-148b on cckbr protein levels, no effect on the cckbr mrna level was detected by qrt-pcr . 21859927_1 protein expression of p53 upregulated modulator of apoptosis , a potential target of mir-483-3p, was significantly decreased in acc, and inversely correlated with mir-483-3p expression. 21258340_1 we find that mir-430 regulates sdf1a and cxcr7 mrnas. 21258340_2 these results indicate that the ligand and the decoy receptors cxcr7a/b are more strongly regulated by mir-430 than cxcr4a/b and sdf1b . 21258340_3 three lines of evidence indicate that tps interfere with the regulation of sdf1a and cxcr7 by mir-430. 21258340_4 these results suggest that mir-430 regulation of endogenous sdf1a and cxcr7b plays a role in pgc migration. 21258340_5 thus, mir-430 is required to modulate the amount of sdf1a rna and to shape its expression pattern by clearing transcripts from old expression domains. 21258340_6 these results indicate that mir-430 and cxcr7b act together to modulate sdf1a mrna expression and protein levels, respectively. 26617737_1 however, the high level of mir-135b was associated with increased expression of foxo1 in cervical cancer cells. 26617737_2 further study by luciferase reporter assay demonstrated that mir-135b could directly target foxo1. 26711789_1 further, functional analyses showed that snp rs7213430 is within the mir-101 seed-binding region, and the variant g allele could lead to significantly lower luciferase activity and brip1 mrna expression, compared to the a allele with the presence of mir-101. 26711789_2 our results suggested that snp rs7213430 in the 3'-utr of brip1 might contribute to scchn susceptibility by affecting the binding activity of mir-101 and resulting in a decreased brip1 expression. 21191961_1 transfection of hacat cells with pre-mir-21 significantly suppressed a luciferase reporter including the cdk2ap1-3'-utr, whereas transfection of tca8113 with anti-mir-21 increased activity of this reporter. 23686497_1 figure 3 mir-155 directly targets ets1 in th17 cells. 23686497_2 together, these results identify ets1 as a direct target of mir-155 in th17 cells. 23686497_3 taken together, these results indicate that ets1 is a functionally relevant target of mir-155 in th17 cells. 21697510_1 we find that many plasticity-associated genes contain predicted mir-485 binding sites and further identify the presynaptic protein sv2a as a target of mir-485. 21697510_2 furthermore, transcript levels for sv2a 3'-utr constructs were reduced by mir-485 , consistent with a degradative mechanism for the mirna. 22538858_1 luciferase reporter assays validated mimecan as a bona fide mir-22 target. 22538858_2 in conclusion, we identified cardiac mir-22/mimecan co-expression and validated mimecan to be a direct target of mir-22 in cardiac fibroblasts. 26065676_1 in a previous study, cheng et al. confirmed that mir-199a could target cd44 via a mir-199a-binding site in the 3'-utr. 26065676_2 the human mir-199a was cloned and transfected into ovarian cics and the results found that cd44 mrna and protein expression was significantly decreased in mir-199a-transfected ovarian cics as compared with mir-199a mutant-transfected and untransfected cells. 26242266_1 these data demonstrated that mir-449b-5p could directly bind to neat1 at the mirna recognition site. 26242266_2 figure 3c indicates that the knockdown of neat1 significantly increased the expression level of mir-449b-5p . 26242266_3 meanwhile, overexpression of neat1 decreased mir-449b-5p expression in both glioma cell lines 25349304_1 moreover, mir141 regulated expression of cxcl1 in lung cancer cells, whereas the luciferase test confirmed that cxcl1 is a target of mir141. 25349304_2 these data indicated that mir141 could regulate the expression and production of cxcl1 in lung cancer cells. 25349304_3 mir141 regulates expression of cxcl1 in lung cancers. 25427583_1 upregulation of mir-205 expression caused the downregulation of zeb2 and vimentin, and the upregulation of e-cadherin in achn cells. 23069658_1 we found that mir-124 directly targets the androgen receptor and subsequently induces an upregulation of p53; mir-124 is significantly downregulated in malignant prostatic cells compared to benign cells, and dna methylation causes the reduced expression of mir-124; and mir-124 can inhibit the growth of cap cells in vitro and in vivo. 23069658_3 figure 1d, transfection of mir-124 mimic resulted in 40% reduction of the enzyme activity, indicating a direct interaction between mir-124 and ar mrna. 21297634_1 we demonstrate that lin-28 bindsdogenous primary let-7 transcripts co-transcriptionally. the correlation between decreased pri-let-7 levels and increased pre- and mature let-7 levels in lin-28 mutant worms suggests that lin-28 normally functions to block primary to precursor let-7 processing during development in c. elegans. 13130513_1 psza11q14 is located within the first intron of the dlg-2 gene and transcribed in the opposite direction to dlg-2. 13130513_2 these results suggest that psza11q14 may be considered a candidate gene for schizophrenia acting as an antisense regulator of dlg-2. 21419107_1 we also found that mir-10b induced glioma cell invasion by modulating tumor invasion factors mmp-14 and upar expression via the direct targethoxd10. 26229009_1 since mir-214 exerts inhibitory actions on the ccn2 3'-utr , these results suggested that twist1 transcriptionally activates mir-214 which then acts to suppress ccn2 mrna levels. 26229009_2 transfection of the cells with twist1 resulted in reduced ccn2 mrna expression or protein production but this was reversed by co-transfection of the cells with a mir-214 antagomir showing that ccn2 inhibition by twist1 is indirect and mediated through mir-214. 19419954_4 we show that mir-21 is upregulated via the mapk pathway upon stimulation of her2/neu signaling in breast cancer cells, and over-expression of other erk1/2 activators such as rasv12 or id-1 is sufficient to induce mir-21 up regulation in her2/neu negative breast cancer cells. 23224365_1 this elevated expression results in increased ifn-alpha1 mrna stability because of the cytoplasmic interaction of the as rna with the mrna at the single-stranded region. 23224365_5 these data thus indicate that mir-1270 and ifn-alpha1 as rna may compete for binding to ifn-alpha1 mrna. 19530237_1 we found evidence that hsa-mir-127 is involved in b-cell differentiation process through posttranscriptional regulation of blimp1 and xbp1. 22729175_1 in conclusion, the combined use of bioinformatic prediction tools, deep sequencing and qrt-pcr analyses identified a gradient of mir-7a opposing the expression of pax6 protein in the neurogenic compartment of the postnatal and adult svz. 22729175_2 hus, repression of pax6 by mir-7a in the lateral wall is necessary to control the rate of dopaminergic neuron production in the olfactory bulb . 22729175_3 figure 5 mir-7a controls pax6 expression through its 3- utr in vivo. 22729175_4 these results suggest that mir-7a binding to the pax6 3- utr is sufficient to downregulate pax6 protein along the lateral ventricle in vivo. 26111928_1 cx43 and bdnf are well known targets of mir-1. 26111928_2 we therefore analyzed the protein expression of cx43 and bdnf in sciatic nerves and drg. 23435381_2 in contrast, suppression of the ptenpg1 lncrna released mirnas, which instead led to destabilization of pten. 22095742_1 using quantitative real-time rt-pcr, we found that mir-17-92 expressed in pmcs and decreased from embryonic day 12 to e14 in palatal shelves. 22095742_2 mtt assay and western blot showed that mir-17-92 inhibited tgfb1 induced proliferation inhibition and collagen synthesis in pmcs by decreasing tgfbr2, smad2, and smad4 protein level. 22095742_3 further luciferase assay showed that mir-17 and mir-20a directly targeted 3' utr of tgfbr2, and that mir-18a directly targeted 3' utr of smad2 and smad4. 22095742_4 these results indicate that mir-17 and mir-20a might targettgfbr2, and that mir-18a might targetsmad2 and smad4 in pmcs. 22095742_5 these results indicate that tgfbr2 is a direct target of mir-17/20a in pmcs. 22095742_6 these results indicate that smad2 and smad4 are direct target of mir-18a in pmcs. 26395571_1 mir-200 down-regulated bmp4 via direct targeting of the gata4 and gata6 transcription factors that stimulate bmp4 transcription. in the present study, we showed that mir-200 suppresses bmp4 indirectly through the gata4 and gata6 transcription factors and that bmp4 knockdown inhibits cancer cell growth, migration, invasion, and metastasis. 26395571_2 on the basis of these data, we propose that mir-200 down-regulates bmp4 through direct targeting of its transcription factors, gata4 and gata6. 24000294_2 we further discovered that hnf1a-as1 knockdown significantly inhibited cell proliferation and anchorage-independent growth, suppressed s-phase entry, and inhibited cell migration and invasion in multiple in vitro eac models . 24000294_5 consistent to this finding, there was a significant positive correlation between hnf1a-as1 and h19 expression in primary eacs . 26364720_1 to investigate whether cxcr2 is a direct target of mir-22-3p, the 3'-utr of cxcr2 was cloned into a luciferase reporter plasmid. 26364720_2 we subsequently assessed cxcr2 protein levels after transfection of the mir-22-3p inhibitors or malat1-shrna1 into endothelial cells and found that the decreased expression of cxcr2 in response to malat1-shrna1 could be blocked by mir-22-3p knockdown. 26364720_3 these data indicate that malat1 protects endothelial cells partly via competing with mir-22-3p, which results in the upregulation of cxcr2. 23100276_1 ectopic expression of mir-214 reduced cell growth and induced apoptosis of myeloma cells.mir-214 26196694_1 the basal levels of akt1, akt2 and total akt were higher in the mir-150 ko hepatocytes compared to the wt hepatocytes . 26196694_2 these findings suggest that the levels of akt1 and akt2 in hepatocytes are influenced by mir-150. 26196694_3 as akt1 and akt2 each contain a single mir-150 binding site in 3'-utr, we generated reporter constructs containing 3'-utr of akt1 and akt2 with mutation of the mir-150 binding site. 26196694_4 mir-150 mimic significantly decreased the 3'-utr luciferase reporter activity of akt1 and akt2; this effect was abolished when the mir-150 binding site was mutated. 26196694_5 these observations demonstrate that both akt1 and akt2 are direct targets of mir-150 in mouse primary hepatocytes. 23296799_1 mir-199b-5p direct target her2 in breast cancer cell. 23296799_2 nevertheless, qrt-pcr analysis of her2 showed that mir-199b-5p had no effect on the her2 mrna level . 23296799_3 these results strongly suggest that mir-199b-5p negatively regulates her2 expression at the translational level. 23296799_4 these results strongly suggest that overexpression of mir-199b-5p in her2-positive breast cancer cells can interfere with the aggressive phenotype by direct suppressing her2 expression. 23296799_5 moreover, the mutation of the mir-199b-5p binding site in her2-3'-utr prevented the down-regulation of luciferase expression, supporting the evidence that mir-199b-5p can direct bind 3'utr of her2 in breast cancer cells, and that the "seed site" was necessary for the binding. 22294691_1 among those, mir-24, mir-145, and mir-210 were down-regulated in tregs compared with controls and were found to have potential target sites in the 3'-utr of foxp3 and ctla-4; mir-24 and mir-210 negatively regulated foxp3 expression by directly binding to their two targetsites in its 3'-utr. 22294691_2 altogether, these results demonstrate the role of mir-24 and -210 in the regulation of foxp3 expression through direct binding to their target sites. 22294691_3 taken together, these results show that mir-145 directly target ctla-4 3'-utr. 22294691_4 these results demonstrate that foxp3 expression and protein levels are inversely proportional to mir-24 and mir-210 expression levels. 22294691_5 these results indicate that ctla-4 expression is negatively regulated by mir-145. 23263745_1 therefore, we examined the expression levels of mir-183 in various types of gliomas and the association of mir-183 with isocitrate dehydrogenase 2 , which has complementary sequences to mir-183 in its 3'-untranslated region . 23263745_2 fig.3 the 3'utr of idh2 mrna is a direct target of mir-183. in conclusion, the major findings presented in this study are that mir-183 directly target the 3'utr of idh2 mrna in glioma cells, which induces the downregulation of idh2 and the upregulation of hif-1a. 21672525_1 taken together, mir-192 could suppress the expression of ercc3 and ercc4 by directly binding the targetsites in their 3'-utrs. 21672525_2 however, the luciferase activity with xpa 3'-utr or its mutant form was not altered after mir-192 transfection . 21672525_4 these results suggested that ercc3 and ercc4 but xpa were direct target of mir-192. 21672525_5 these results indicated that mir-192 reduced the expression levels of ercc3 and ercc4. 18376396_1 all five members of the microrna-200 family and mir-205 were markedly downregulated in cells that had undergone emt in response to transforming growth factor -beta or to ectopic expression of the protein tyrosine phosphatase pez. 18376396_3 together, these micrornas cooperatively regulate expression of the e-cadherin transcriptional repressors zeb1 and sip1 , factors previously implicated in emt and tumour metastasis. 18376396_4 inhibition of the micrornas was sufficient to induce emt in a process requiring upregulation of zeb1 and/or sip1. 18376396_7 expression of the mir-200 family was also lost in regions of metaplastic breast cancer specimens lacking e-cadherin. 26799933_1 the functioning of ecfcs is improved by fir treatment and this occurs via a reduction in the level of mir-134 and an increase in the nrip1 transcript, a direct target of mir-134. 26799933_2 these findings suggested that mir-134 directly targets the 3- utr of nrip1 to attenuate angiogenic activity of ecfcs in vitro. 26799933_3 these results suggest that nrip1 is a direct target of mir-134 and is involved in ecfcs functioning. 21203553_1 by searching mirbase, we found that mnsod, gpx2 and trxr2, three important mitochondrial antioxidant proteins that are essential for detoxification of o2. and h2o2, are potential targets of mir-17*. 21203553_2 to verify that mir-17* is able to repress antioxidant proteins, mature mir-17* was transfected into pc-3 cells, which have a low level of endogenous mir-17*. the expression of the three antioxidant proteins was reduced by the transfected mir-17* in a dose-dependent manner. 21203553_3 transfection of mir-17* into prostate cancer pc-3 cells significantly reduces levels of the three antioxidant proteins and activity of the luciferase reporter under the control of mir-17* binding sequences located in the 3'-untranslated regions of the three target genes. 26662303_1 mechanically, the 3- -untranslated regions of sirt1 were a direct target of mir-22, leading to the decreased expression of sirt1 protein in u87 and u251 cells. 26662303_2 these findings indicated that the 3'-utr of sirt1 is a direct mir-22 target, by which mir-22 affected the expression of sirt1, leading to loss of cell function. 25368993_2 using mir target prediction algorithms and a filtering strategy, rab5c was predicted as a potentially relevant target of mir-509. 25368993_3 enforced mir-509 expression in nalm6 cells reduced rab5c mrna and protein levels, and rab5c was demonstrated to be a direct target of mir-509. 25368993_4 knockdown of rab5c in nalm6 cells recapitulated the growth inhibitory effects of mir-509. 19956871_1 mir-15b inhibitor transfection increased hcc cell proliferation and inhibited trail-induced apoptosis, while mir-15b precursor transfection decreased proliferation and enhanced apoptosis. 19956871_2 bcl-w was identified as a target molecule regulated by mir-15b. 21768308_1 using a novel ms2-tagged rna precipitation method,we identified microrna mir-548c-3p as a mediator of these effects and furtheruncovered that the interaction of mir-548c-3p with the top2a 3'utr repressed top2a translation by antagonizing the action of hur. 21768308_2 similarly, incubation of cells with l-azidohomoalanine followed by labeling of nascent proteins with alkyne-biotin and western blot analysis to detect newly synthesized proteins further showed that mir-548c-3p lowered top2a translation . 21768308_3 in sum, mir-548c-3p interacts with the top2a 3'-utr and reduces top2a translation. 21768308_4 together these findings indicate that hur antagonizes mir-548c-3p, thereby enhancing top2a expression. 21768308_5 importantly, mutation of the mir-548c-3p site totally abrogated the repressive influence of mir-548c-3p, indicating that mir-548c-3p acted through the predicted top2a 3'-utr site. 24211739_1 there was a negative correlation betweenexpression levels of mir-101 and ezh2. 24211739_2 luciferase assay results confirmed ezh2 asa direct target gene of mir-101, which negatively regulates ezh2 expression inhcc. 23056576_1 igf1r is a direct target of mir-122 in bc cells. 23056576_2 taken together, our data identified igf1r as a direct mir-122 targetand suggested that mir-122 overexpression suppresses the expression of igf1r in mcf-7 cells. 23056576_3 mir-122 inhibits cell proliferation and tumorigenesis of breast cancer by targeting igf1r. 23056576_4 we observed that the relative luciferase activity of the reporter which contained wild-type 3'-utr of igf1r was significantly inhibited in mir-122 group compared to ev group. 23447532_1 the reduction in grb2 levels ranged from 20% to 5-fold with increasing concentrations of mir-378 , thus suggesting that grb2 is a valid target of mir-378. 23447532_2 these data suggested that grb2 and not erk2 is a valid target of mir-378. 23447532_3 these results demonstrated that mir-378 targets grb2 by causing translation inhibition as well as promoting its mrna degradation. 26361355_1 further experiments using luciferase reporter assay confirmed that mir-137 could act on specific sites in 3' utr region of d2r, nmdar2 and gaba-b-r3, which downregulated significantly in pd flies. 26361355_4 taken together, these results indicate that nmdar2, d2r and gaba-b-r3 are direct targets for dme-mir-137-3p. 22904669_1 furthermore, the interactions of mir-1981 and its targetgenes, bcl-2 and bid, were validated by luciferase assay. 22904669_2 the results show that mir-1981 mimic up-regulated the luciferase activity of psicheck-2 bcl-2 3'utr, but the luciferase activity of psicheck-2 bid 3'utr was not changed significantly. 22904669_3 as shown in figure 6a, the mir-1981 mimic and mutant mir-1981 mimic were employed to confirm the mir-1981 binding site in bcl-2 mrna 3'utr. 25644061_1 mir-31, in turn, targets sox4 for degradation by directly binding to its 3'-utr. 25644061_2 taken together, these results demonstrate that sox4 is a direct target of mir-31, while ezh2 and hdac3 are indirect targets. 25644061_3 our results indicate that mir-31 down-regulates sox4 by binding to its 3'-utr in eac and escc cells. 22925886_1 the computational programs miranda and targetscan identified p21 and p57 as predicted targets for mir-702 and mir-320, respectively . . to experimentally ascertain whether mir-702 and mir-320 target p21 and p57, we constructed luciferase reporters that test direct binding of mirna to predicted target sequences within the 3'-utr. 23097274_1 lin-41 is a stem cell-specific e3 ligase and a known target of the tumour suppressor microrna let-7. 23097274_2 after co-transfection with let-7g, lin-41 activated the luciferase activity of the let-7 reporter, but not the reporter with a mutated seed sequence , indicating that lin-41 inhibited the function of let-7 in gene silencing. 23097274_3 interestingly, lin-41 itself is a target of let-7 microrna, and the protein level of lin-41 is regulated by lin-28b. 25681036_1 we confirmed that wif1 and ctnnbip1 are bona fide targets of mir-603. 25681036_2 taken together, these results suggest that mir-603 directly targets wif1 and ctnnbip1. 26163462_1 our results provide strong evidence that caln1 is a target of mir-137. 26163462_2 computational prediction of caln1 as a target of hsa-mir-137. 25489007_1 these data illustrated that mir-218 and mir-195 directly target the 3'-utr of stxbp1 mrna. 25489007_2 these results demonstrate that mir-218 and mir-322 negatively regulate the expression of stxbp1 protein. 25109742_1 furthermore,overexpression of mir-101 significantly increased the anti proliferative effects and apoptosis induced by cisplatin, whereas knockdown of mir-101 significantly decreased the anti proliferative effects and apoptosis induced by cisplatin. 25109742_2 in addition, downregulation of mir-101 induced cell survival and cisplatin resistance through the upregulation of cox 2 expression. 25109742_3 luciferase gene reporter assays confirmed that cox 2 was a direct target gene of mir-101. 21687927_1 the results presented here suggest that dspp is regulated post-transcriptionally by mir32, mir885-5p and mir586 during odontoblast differentiation. 21687927_2 figure 7. qrt-pcr for dspp and mir32, mir885-5p and mir586 at different times during mineralized culture of dental pulp cells. 22195016_1 a conserved and functional binding site for mir-133 was identified in the 3'untranslated region of igf-1r. 22195016_2 figure 1 identification of a functional mir-133 binding site in the igf-1r 3'-utr. in contrast, igf-1r transcript remained at a constant level from day 4, suggesting a posttranscriptional regulation of igf-1r mrna. 22195016_4 these data demonstrate that mir-133 represses igf-1r at the posttranscriptional level . 22195016_5 these results indicate that ectopically expressed mir-133 represses igf-1r translation to reduce overall pi3k/akt signaling. 26221215_1 p53 was a direct target of mir-300 in gastric cancer cells. 26221215_2 mir-300 targeted p53 by binding to its 3'-utr. 25295122_1 bmi-1 was predicted as a potential target of mir-183 by targetscan and miranda. 25295122_2 the 3'-utr of bmi-1 contains the binding site for the seed region of mir-183. 25295122_3 the ectopic expression of mir-183 significantly reduced the bmi-1 mrna and protein levels in the sgc7901 and ags cells. 25295122_4 the luciferase activity of the reporter in the vector containing the bmi-1 3'-utr wt was significantly reduced by mir-183 mimics ; however, the luciferase activity of the bmi-1 3'-utr mt was not significantly affected. 22119192_1 to determine whether mir-106b directly affects abca1 expression by targeting its 3- utr region, we performed a luciferase reporter assay with the full-length habca1 3- utr. 22119192_2 collectively, our data suggest that mir-106b directly regulates abca1 expression by binding to the 3- utr of abca1 and repressing its translation. 22119192_3 taken together, our data demonstrate that mir-106b suppresses abca1 expression in cells derived from human, rat, and mouse. 26349981_1 in the present study, mir-143 was firstly identified as a autophagy inhibitor in gc cells via targeting gabarapl1. 26349981_2 in conclusion, we determined mir-143 as a potent inhibitor of autophagy via targeting gabarapl1 and mir-143 could improve the efficacy of quercetin though autophagy inhibition in gc cell lines, thus representing a novel potential therapeutic target for gastric cancer. 26349981_3 results indicated that the expression of mir-143 was significantly down-regulated in the tissues of gc tissues and mir-143 was firstly identified as a autophagy inhibitor in gastric cancer cells via targeting gabarapl1 , which is a ubiquitin-like protein required for the formation of autophagosomal membranes. 23851509_1 with dual luciferase reporter assay, we revealed that mir-30a could bind to the 3'-untranslated region of metadherin gene, thus exerting inhibitory effect on mtdh. 23851509_2 taken together, our findings indicated mir-30a inhibits breast cancer proliferation and metastasis by directly targeting mtdh, and mir-30a can serve as a prognostic marker for breast cancer. 23851509_3 furthermore, re-expression of mir-30a profoundly reduced cell invasion in mda-mb-231 psuper control cells but not in mda-mb-231 shmtdh cells, indicating that mtdh is a functional target of mir-30a. 23851509_4 these results reinforce the idea that mtdh is a direct and functional target of mir-30a. 23035210_1 either transient expression of mir-34a synthetic mimics or lentivirus-based mir-34a-stable enforced expression triggered growth inhibition and apoptosis in mm cells in vitro. 23035210_2 synthetic mir-34a downregulated canonic targets bcl2, cdk6, and notch1 at both the mrna and protein level. 22068816_1 pnp as a target of post-transcriptional repression by mir-1 and mir-133a. 22068816_2 the luminescence intensity significantly decreased in the presence of either sites targeted by mir-1 or mir-133a, while the luminescence intensity was not decreased when the seed sequence of both targetsites was deleted from the vectors . 22068816_3 these data suggest that mir-1 and mir-133a directly bindto specific sites on 3'-utr of pnp mrna. 22068816_4 figure 3 pnp expression was suppressed by mir-1 and mir-133a transfection at both the mrna and protein levels in pca cell lines, pc3 and du145. 23647386_2 compared with a negative control group, treatment with antagomir-21 significantly increased apoptosis following sci. 23647386_3 pro-apoptosis genes fasl, pten and pdcd4 were proved to be direct targets of mir-21 in many diseases and cell types. 23376683_1 these data indicate that a purkinje cell-specific increase in mir-150 levels occurs concomitantly with a decrease in its targets rgs8 and vegfa. 22750473_1 in this study, we used computational and expressional analysis to identify that the 'seed sequence' of mir-410 matched the 3' utr of the met mrna. 22750473_2 besides, the expression of mir-410 was inversely associated with met in human glioma tissues. 22750473_3 using luciferase and western blot assay, we certified that mir-410 directly targeted met in glioma cells. 22750473_4 fig. 1. met is direct target of mir-410 in glioma cells. 22750473_5 these data suggest that mir-410 bind to the 3' utr of met and impair met mrna translation. 22750473_6 these data indicated that mir-410 reintroduction supressed met and tumor survival in vivo. 21151097_1 in the undifferentiated state, both oct4 and the oct4-induced mir-302 directly repress nr2f2 at the transcriptional and post-transcriptional level, respectively. 21151097_2 nr2f2 is a bona fide mir-302 target to address a specific role for mir-302 in the regulation of nr2f2 during hesc differentiation, we took advantage of a mir-302-overexpressing hes cell line . 21151097_4 as undifferentiated cells hold high levels of mir-302, such discrepancy might be due to the post-transcriptional inhibition of nr2f2 translation by mir-302. 23399934_1 in addition, through luciferase reporter assays and western blot analyses, dna methyltransferase 3a was identified as a directly regulated target of mir-370. 23399934_2 furthermore, dnmt3a was identified as a mir-370 target gene that may be mediated in the process of mouse embryonic generation. 23399934_3 given that mir-370 targets dnmt3a and the mir-370 knockin mice are available, the roles of mir-370 during development and in tumorigenesis in vivo should be determined in further studies. 26798048_1 dual-luciferase reporter assay confirmed that mir-93 bound to the three prime untranslated region of epha4 and inhibited the expression of epha4 mrna. 26798048_2 these findings provide evidence that mir-93 inhibits epha4 expression, decreased epha4 expression could promote neurite outgrowth in scns due to reduced levels of p-ephexin and active rhoa. 26798048_3 these results provide evidence that epha4 is the putative target gene of mir-93. 21897363_1 conversely, egr2 itself is targeted by mir-17-92, indicating existence of mutual regulatory relationship between mir-17-92 and egr2. 21897363_2 furthermore, restoring egr2 levels in primary acute myeloid leukaemia blasts expressing elevated levels of mir-17-92 and low levels of pu.1 and egr2 leads to downregulation of mir-17-92 and restored expression of its targets p21cip1 and bim. the group with elevated levels of mir-17-92 expressed significantly lower levels of the bim and p21 mrnas displaying negative correlation between mir-17-92 and both bim and p21 expression, suggesting that bim and p21 are targets of mir17-92 in aml and their deregulation may be involved in pathogenesis of aml . 19022373_1 moreover, consistent with the down-regulation of mir-378, hne also induced the expression of the sufu protein, a tumor suppressor recently identified as a target of mir-378. 19022373_2 among the three mirna modulated by hne treatment, confirmed by quantitative real-time rt-pcr, only the target for mir-378 have been recently validated. 19022373_5 indeed, in agreement with mir-378 down-regulation, hne induced sufu protein expression in hl-60 cells, at 8 h from the beginning of treatment . 21415464_1 we report here that down-regulation of mir-34a, -30e, and -181a permits their shared target gene expression to remain at a high level without post-transcriptional repression, accompanied by concomitant low levels of bax expression and caspase cleaving; 26391398_1 these results thus validate that ripk2 and map3k7 are direct targets of mir-150 and mir-143 respectively. 26159252_1 in addition, rs6218 cc genotype was associated with increased level of igf1 mrna in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-mir-603 and hsa-mir-3941 in the 3'utr of igf1. 26781064_1 moreover, we confirmed that ezh2 was also a direct target of mir-26a in hcc cells, thus, creating a double-negative feedback loop. 26781064_2 these results suggest that ezh2 is a direct target of mir-26a in hcc cells. 26781064_3 figure 4. ezh2 is a direct target of mir-26a in hcc cells. 26781064_4 taken together, our results suggest that the double-negative feedback loop between ezh2 and mir-26a regulates hcc cell growth. 19400782_1 here, we extend the omp-srna network by showing that the expression of the omp ybfm is silenced by a conserved srna, designated micm . 26812136_1 mcpip1 is significantly up-regulated after asci. the negative relationship between mcpip1 and mir-9 suggest that mcpip1 mrna could be a target of mir-9 during asci. in conclusion, we provide evidence that mcpip1 is significantly up-regulated in asci, which leads to apoptosis of neurons. 26812136_2 the negative relationship between mcpip1 and mir-9 was also shown in this study from our results that mrna of mcpip1 was a target of mir-9 in asci. 26191213_1 to explore the underlying mechanisms through which mir-107 promote the proliferation of hcc cells, we used publicly available algorithms to predict the potential targets of mir-107 and axin2 was predicted to be one of its targets . 26191213_3 western blot showed that the expression of axin2 was notably decreased in cells transfected with mir-107 mimics . 26191213_4 these data demonstrated that mir-107 might acts its oncogenic role in hcc via inhibiting the expression of axin2. 21799743_1 thus, our studies demonstrated that mir-145 is a key negativeregulator of chondrogenic differentiation by directly targeting sox9 at earlystage of chondrogenic differentiation. 21799743_2 noticeably, we found sox9 was the potential targetgene regulated by mir-145. 21799743_3 according to the primary role of sox9 in the process of mscs differentiation into chondrocytes, we hypothesized that sox9 may be inhibited by mir-145, which prevents mscs from differentiating into chondrocytes. 21799743_4 taken together, our data suggest that mir-145 could targetsox9 by binding the mres within the sox9 mrna 3'-utr. 21799743_5 thus, these data demonstrate mir-145 inhibits sox9 protein expression but not mrna levels in mesenchymal stem cell line at early stage of chondrogenic differentiation. 26245343_1 mir-224 was significantly overexpressed in esophageal intraepithelial neoplasia and escc tissues, while the expression of phlpp1 and phlpp2 proteins, the target genes of mir-224, was downregulated in escc tissues. 26245343_2 mir-224 expression was associated with advanced clinical tnm stage, pathologic grade, and the level of phlpp1 and phlpp2 proteins in escc tissues. 26245343_3 mir-224 was able to bind to the 3' untranslated region of phlpp1 and phlpp2 mrna to suppress their expression. 26032092_1 mir-208 targets 3'-utr of cdkn1a to inhibit its expression. 26083618_1 mir-26b targets associated with dapk. 26083618_2 mir-26b directly targets dip1, which in turn leads to the upregulation of cellular dapk protein level. 22262409_1 we investigated the regulation of pten, cdkn1a/p21 and timp2 by two other c19mc members deregulated in hccs, mir-519a and mir-519c- 3p. a direct bindsg of mir-519a and mir-519c-3p to the 3' utrs of these targetgenes was demonstrated by a luciferase-reporter assay. 22262409_2 mir-519d target pten, akt3 and cdkn1a/p21 in hcc. 22262409_3 these findings suggest that mir-519d participates to the post-transcriptional regulation of cdkn1a/p21, pten and akt3 in hcc. in addition, we investigated the regulation of pten, cdkn1a/p21 and timp2 by two other c19mc members deregulated in hccs, mir-519a and mir-519c-3p. 22262409_4 a direct bindsg of mir-519a and mir-519c-3p to the 3' utrs of these targetgenes was demonstrated by a luciferase-reporter assay . 22262409_5 accordingly, western blot and rt-pcr analysis confirmed the modulation of pten, cdkn1a/p21 and timp2 by both mir-519a and mir-519c-3p . 22262409_6 moreover, a functional analysis on hepg2 and snu475 cells showed that mir-519d regulates timp2 mrna expression . 26297546_1 additionally, ppp2r2a was identified as a direct target of mir-556-5p. 26297546_2 our data strongly suggested that mir-556-5p negatively regulates ppp2r2a expression via direct binding to putative binding sites in the 3 ' -utr region. 26297546_3 furthermore, our finding revealed that mir-556-5p contribute to cell proliferation of prostate cancer be mediated through downregulation of ppp2r2a, proposing that mir-556-5p might be used as a novel therapeutic target of prostate cancer. 26620678_1 furthermore, luciferase reporter assays and western blotting demonstrated that mir-193a-3p directly targets mmp14. 26620678_2 mir-193a-3p inhibited idd in vitro and in vivo. 23650073_1 we validated the mrnas encoding mecp2 and x-linked inhibitor of apoptosis as targets of mir-181. 23650073_2 we have identified two novel targets of mir-181, mecp2 and xiap, as well as a non-canonical potential target, hmga1. 23650073_3 mecp2 was validated as a mir-181 target showing a 72% reduction in light units . 23534758_2 hoxa1 was identified as a novel target of let-7c. 23534758_3 mts, colony formation and flow cytometry assays demonstrated that forced expression of let-7c inhibited nsclc cell proliferation by inducing g1 arrest in vitro, consistent with inhibitory effects induced by knockdown of hoxa1. 24040078_1 moreover, the dual luciferase assay revealed that stat3 was directly targeted by mir-130b, which was further confirmed by the inverse expression of mir-130b and stat3 in pancreatic cancer samples.mir-130b is a prognostic marker and inhibits cell proliferation and invasion in pancreatic cancer through targeting stat3. 20190813_2 these results indicated that p21cip1/waf1 can be regulated by mirnas other than mir-93, mir-20a/b, mir-17 and mir-106a/b. 18372920_1 overexpression of mir-21 in mcf-7 human breast cancer cells and mouse epidermal jb6 cells promoted soft agar colony formation by downregulating pdcd4 protein levels 25034767_1 to further investigate this potential target of mir-19b, we generated a pgl3-promoter ctnnb1 3'-utr mir-19b target reporter construct. 25034767_2 we found that luciferase activity was decreased after microinjection of pgl3-promoter ctnnb1 3'-utr and mir-19b mimic compared with microinjection of pgl3-promoter ctnnb1 3'-utr , indicating that mir-19b directly targets ctnnb1. 25034767_3 we measured the expression level of ctnnb1 using qpcr and in situ hybridization and confirmed that the expression level of ctnnb1 is negatively correlated with mir-19b expression . 25034767_4 these results suggest that overexpression of mir-19b induces the inhibition of the wnt signaling pathway by directly targeting ctnnb1. 20395292_1 we found that inhibition of endogenous mir-101 significantly up-regulated app protein levels , indicating that hippocampal app expression may be regulated by mir-101. 20395292_2 immunofluorescence and western blot analysis demonstratd that increases in mir-101 level strongly down-regulated app protein levels. 20395292_3 a corresponding slight down-regulation of app mrna was observed , suggesting that although mir-101 may act primarily by reducing app translation it may also affect app mrna stability. 26297547_1 the data suggested that pdgfra was a target gene of mir-140-5p in ovarian cancer cells. 26297547_2 mir-140-5p down-regulates pdgfra expression in ovarian cancer cells posttranscriptionally 23967091_1 mir-140 can suppress the tgf--beta1 pathway through targeting smad3 in the c3h10t1/2 and 3t3 cell lines , . 23967091_2 these results confirm that mir-140 downregulates smad3 expression by binding to smad3-3- utr in aecs. 23967091_3 these results induced by mir-140 are similar to those affected by ptx treatment, which indicates mir-140 participates in the antifibrotic process by downregulating the expression of smad3 and prevents its subsequent phosphorylation in aecs. 26399639_1 downregulation of prkag3 by mir-132. 26399639_2 mir-132 specifically bound to the 3'-utr of prkag3. 26399639_3 prkag3 was the downstream target of mir-132. 26758430_1 the results of luciferase assay indicated that mir-340 could directly target 3'-utrs of ctnnb1, rock1, and c-myc . 26758430_2 accordingly, we demonstrated that mir-340 inhibits ctnnb1, c-myc, and rock1 by direct interaction with their 3'-utrs. 26872979_1 furthermore, during chondrogenesis, dll4 expression was found to significantly decrease at both mrna and protein levels, which was negatively regulated by mir-30a through directly targeting the 3'utr of dll4. 26872979_2 these findings indicate that mir-30a can directly target dll4 through binding to its complementary seed sequences in the 3'utr of dll4. 26872979_3 collectively, our data suggests that mir-30a can directly target the 3'utr of dll4 to suppress dll4 translation. 22870299_1 we show that the proinflammatory cytokine interleukin 1 alpha is a targetfor mir-142-3p and the oncogenic bcl6 for mir-205. 22870299_5 the results are compatible with a down-regulation of bcl6 due to an up-regulation of the mir-205 which target this mrna. 26324892_1 these results supported the bioinformatic predictions confirming the direct targeting of mir-15b/16-2 on the ccnd2 and igf1r 3- utr. 21385766_1 slit-robo rho gtpase activating protein 2 , a downstream component of slit/robo signaling, was also identified as a potential target of mir-218. in contrast to robo1 and robo2, its putative target site in the 3- utr was not as highly conserved across phyla . 18162065_1 etoh induces mir-212 over-expression which causes gut leakiness by down-regulating zo-1 translation. 22102413_1 we show that mir-145 directly represses sox9 expression in human cells through a unique binding site in its 3'-utr not conserved in mice. 22102413_2 such mir-145 overexpression greatly decreased the levels of sox9 both at the mrna and particularly at the protein level . 22102413_3 interestingly, overexpression of mir-145 appeared to have a greater impact in hypoxic conditions and largely prevented the increase in sox9 expression induced by hypoxia. 22102413_4 mir-145 inhibition resulted in increased sox9 protein levels , without significant changes in sox9 mrna levels . 22102413_5 furthermore, mir-145 overexpression reduced by 2-fold the expression of a luciferase reporter containing wild type sox9 3'-utr. 22102413_6 figure 3. mir-145 directly inhibits sox9 expression in human chondrocytes through a specific binding site located in 3'-utr. in the present study, overexpression of mir-145 markedly reduced both h19 and mir-675 levels in human chondrocytes, probably indirectly through sox9 down-regulation . 26041881_1 these data clearly demonstrate that mir-23b regulates notch2 receptor and ets1 expressions through targeting their 3'-utrs. 23572380_1 previous studies showed that notch2 was involved in gscs proliferation, while our recent studies on notch2 as a target gene of mir-107 in glioma cells suggested that mir-107 may also modulate notch2 expression in gscs. 23572380_2 western-blotting showed that mir-107 suppressed notch2 protein expression in cd133 + u87 cells . 23572380_3 these data suggest that mir-107 can inhibit the growth of cd133 + u87 cells through down-regulation of notch2 protein, and cd133 and nestin mrna expression. 23509296_1 mir-9 down-regulates foxo1 and foxo3 genes, and overexpression of foxo3-3a inhibits myeloid cell differentiation induced by mir-9. 23509296_2 qrt-pcr analysis of the foxo1 and foxo3 gene expression in bm cells infected with vector or mir-9 retroviruses. 23509296_3 we determined the expression of foxo1 and foxo3 in mir-9 expressing cells by qrt-pcr, and found that these cells had a reduced expression of foxo1 and foxo3 compared with control cells. 20933506_2 2b and c indicate that the overexpression of mir-335 inhibits the expression of rasa1 mrna and protein by about 23% and 35%, respectively. 20933506_3 this result confirms that the mrna of rasa1 is directly targeted by mir-335. 20933506_4 along with the validation of rasa1 as a target of mir-335 mentioned above, these results indicate that the reduction of mir-335 at least in part causes the upregulation of rasa1 during the ratepididymal development. 26277621_1 overall, four independent assays were performed, resulting in an average 62.2% luciferase activity for mir-375 and 107.2% luciferase with mir-151a-3p, where the luciferase activity of the timm8a 3'-utr vector-only samples were set at 100%. 26277621_2 with this in mind, a luciferase assay was carried out to confirm if mir-151a-5p is able to bind directly to the 3'-utr of sox17 mrna. 26277621_3 we co-transfected a luciferase reporter plasmid containing the sox17 3'-utr into 293ft cells alongside a mir-151a-5p mimic or a mir-151a-3p mimic as a negative control. 26277621_4 as an additional positive control for these assays, we also included a mir-200a mirna mimic, which has also recently been described as binding to sox17 . 26277621_5 these results imply mir-151a-5p can directly bind its predicted target gene sox17. 25716201_1 these data suggest that mir-129 inhibited mmp9 without affecting egfr phosphorylation in response to egf stimulation. 23199328_1 we further found that stat1 mrna targeted by mir-145 was over-expressed and apoptosis inhibitory protein 5 mrna targeted by mir-224 was under-expressed in sle t cells. 26464817_1 interestingly, expression level of irs2, akt2 and insr, directly targeted by mir-215, were upregulated in differentiated cells. 21768388_2 quantitative real-time pcr validated that rybb regulated 16 genes; mica regulated 9 genes; and both srnas regulated 6 genes. 21768388_3 analysis of salmonella rybb established that the highly conserved nucleotides 1-16 of rybb is usually sufficient for target repression, and that regulation critically depends on the gcc motif at the very 5' end of rybb. of the 17 candidate targets predicted to use the r16 region of rybb, 16 of 17 are significantly down-regulated by r16tom . 21768388_4 moreover, rybb-m2 is unable to down-regulate 13 of 14 targets predicted to use rybb c2for interaction , whereas 3 of 4 targets predicted not to use mutation rybb c2 maintain down-regulation. 21768388_6 mrna::gfp fusion assays validated e.coli nmpc, ompc , ompf, fiu and rlud as direct rybb targets. 21768388_10 point mutation and mrna gene reporter assays showed that ompa is subject to both parallel yet in dependent regulation by mica and rybb. 21768388_12 surprisingly, although the nucleotides involved are conserved both between e. coli and salmonella , they found that a m2' allele of e. coli tsx was regulated by neither rybb-m2 nor mica, which indicated that tsx m2'may have an altered mrna structure and that other strategies will have to be used to study dual srna control of this target in e. coli . 25419419_1 luciferase reporter assay confirmed that casp-2 was directly bound by mir-96 in rgc-5 cells, and sirna-regulated silencing of casp2 gene rescued the apoptosis in rgc-5 induced by over-expressing mir-96. 22722835_1 human argonaute proteins also associate with a subset of let-7 primary transcripts, suggesting that this interaction is conserved in higher organisms . 19692702_1 luciferase reporter assays including site directed mutagenesis of binding sites revealed a significant regulation of plag1 by mir-181a, mir-181b, mir-107 and mir-424. 19692702_2 while expression of plag1 mrna was not affected, plag1 protein expression was shown to be significantly elevated in cll cells as compared to the levels in healthy donor b cells. in summary, we could demonstrate disruption of mirna-mediated translational control, partly due to epigenetic transcriptional silencing of mirnas, with subsequent overexpression of the oncogenic transcription factor plag1 as a putative novel mechanism of cll pathogenesis. 25148875_1 furthermore, phosphatase and tensin homologs deleted on chromosome 10 , a negative regulator of pi3k/akt pathway, were confirmed as a direct target of mir-181b. 25148875_2 it is confirmed that pten is a direct target of mir-181b. 25148875_3 these results suggest that pten was a direct target of mir-181b. 25148875_4 in this study, we found that pten was predicted as a target of mir-181b, which was confirmed by the dual luciferase reporter experiment 22210897_1 further investigation disclosed that mir-26a/b directly suppressed the expression of cdk6 and cyclin e1, which resulted in reduced phosphorylation of prb. 22210897_2 further investigation showed that mir-26a/b could also diminish endogenous expression of both cdk6 and cyclin e1 proteins . 22210897_3 moreover, downregulation of mir-26a/b was statistically correlated with overexpression of cdk6 and cyclin e1 in hcc tissues . 22210897_4 these data suggest that cdk6 and cyclin e1 are direct target of mir-26a/b. 26743688_1 these results showed that nob1 is a direct target gene of mir-192. 26743688_2 these results further confirmed that mir-192 targeted and modulated nob1 expression. 26275461_1 mir-1 functioned as a tumor suppressor by targeting k-ras and malat1. 26275461_2 in this study, k-ras and lncrna metastasis-associated lung adenocarcinoma transcript 1 were identified as targets of mir-1. 26275461_4 the luciferase assay and western blot assay further showed that k-ras and malat1 were direct targets of mir-1. 19342689_1 thus, these data collectively indicate that mir-346 inhibits btk expression in lps-activated ra fls. 19342689_2 we also found that in thp-1 cells transfected with mir-346 mimic, btk expression was down-regulated and that mir-346 did not repress btk expression directly, as transfection of hek293 cells with a luciferase reporter fused to btk 3'-utr along with mir-346 mimic did not result in a measurable change in luciferase activity . 19342689_3 taken together, our data indicate an important role for mir-346 and btk in the regulation of il-18 release by ra fls. 22144109_1 we identify vacuole membrane protein 1 as the direct and functional downstream target of mir-210; in addition, we show that its expression is negatively correlated with the expression of mir-210 in hcc. 22144109_2 these results indicate that mir-210 can directly bind to the 3'-utr of vmp1. 22144109_3 furthermore, we showed that mir-210 can suppress the messenger rna and protein levels of vmp1 in hcc cells and that there is dose-dependence between the expression of vmp1 and mir-210 . 22144109_4 taken together, these results indicate that mir-210 can down-regulate the expression of vmp1 in hcc cells by directly binding to its 3'-utr, which illustrates that vmp1 may act as a downstream target of mir-210 in hcc cells. 22144109_5 these observations indicate that vmp1 is frequently down-regulated in hcc samples, and the reduction may be caused by the overexpression of mir-210. 22144109_6 together, the effect of overexpression of vmp1 on hcc cells was the opposite of that of mir-210, and reduction of vmp1 phenocopied the effect of mir-210 on hcc cells, suggesting that vmp1 may be a functional target of mir-210 in hcc. 22144109_7 these results indicated that vmp1 is a bona fide functional target of mir-210 in hcc cells. 22730517_1 using bioinformatic tools , we identified the smad3 gene as a candidate target of mir-23b and mir-29b. 22730517_2 the same reporter construct of the previous experiments, but carrying the insert in antisense orientation, was insensitive to the effects of mir-23b and mir-29b , proving that the modifications of the target sites of smad3 3'-utr are able to block the function of these mirna. 22730517_4 6. smad3 mrna expression is inversely correlated with mir-23b and mir-29b expression in experimental and human goiters. 26206559_1 taken togeter, these data strongly point to the regulation of arg1, cxcl12 and il16 both mrna and protein levels by mir-210 in splenic mdscs. 26206559_2 arg1, il16, cxcl12 and ndrg1 are new valided mir-210 target genes. 26151913_1 to determine whether mir-431 does so by targeting pax7, we overexpressed pax7 in c2c12 cells stably expressing mir-431 . 26151913_2 pax7 overexpression abolished the differentiation induced by mir-431, as indicated by the reactivity and expression of mhc. 26151913_3 together, the unique expression pattern of mir-431 and its binding sites at the 3'-utr of pax7 mrna suggests that mir-431 regulates myogenesis by targeting pax7. 23483142_1 mir-101 inhibited autophagy via targets including rab5a, stmn1 and atg4d. 23157748_1 up-regulation of mir-383 knockdowns the expression of prdx3, inhibits proliferation and promotes apoptosis of daoy cells, leading to increased intracellular ros and decreased levels of mitochondrial membrane potential. 26179126_1 insr gene is a direct target of mir-15b. 26179126_2 overall, this indicates that mir-15b targets insr 3'-utr directly through its binding site and subsequently represses insr expression at the posttranscriptional level. 26179126_3 because insr was found to be an authentic target of mir-15b, the upregulation of mir-15b should repress insr expression, leading to impaired insulin signaling in hepatocytes. 25429777_1 next, we analysed the expression of let-7 target ras genes at the transcriptional and translational levels 48 h after transfection. 18759060_1 we observed selective up-regulation of mirna-221 and down-regulation of a mirna-221 messenger rna target encoding the survivin-1 homolog birc1, a neuronal inhibitor of apoptosis protein and marker for neurodegeneration. 26247736_1 to confirm the direct binding of mir-26a on smad1 and gsk3-beta mrnas, we performed luciferase activity assay by co-transfecting pmir reporter containing the binding sites of smad1 or gsk3-beta 3- utr with pre-mir-26a or anti-mir-26a. 26247736_2 overexpression of mir-26a inhibited the luciferase activity of reporters of smad1 and gsk3-beta, whereas knockdown of mir-26a increased the luciferase activity of both reporters. 26247736_3 real-time reverse transcription-pcr showed that the mrna levels of smad1 and gsk3-beta were not significantly changed after overexpression or knockdown of mir-26a , indicating that mir-26a functions through post-transcriptional regulation. 20075075_1 klf4 mrna is a direct target of mir-10b . 20075075_2 real time quantitative pcr of klf4 mrna showed that mir-10b overexpression or inhibition had no effect on klf4 mrna level , which indicated the post-transcriptional regulation of mir-10b on klf4 mrna. 20075075_3 the decreased klf4 expression in mir-10b overexpressing cells was due to the post-transcriptional regulation of mir-10b. 20815812_1 to demonstrate the effect of curcumin on pre-mir-21 and mir-21 expression and function, quantitative pcr and western-blot analyses were performed for pre-mir-21, mir-21 and pdcd4, which has been shown to be an mir-21 post-transcriptional target , with 24h of curcumin treatment. 18555017_2 by using an integrated approach of in silico prediction and mrna expression analysis, we further characterized stathmin 1 as a putative downstream target of mir-223. 18555017_3 integrative analysis further implicated stathmin 1 as a downstream target of mir-223. 18555017_4 a strong inverse relationship between stmn1 mrna and mir-223 expressions was shown . 18555017_5 a substantial reduction in stmn1 protein was further demonstrated upon restoration of mir-223 expression in hcc cell lines. 18555017_6 we further showed that mir-223 readily could suppress the luciferase activity in reporter construct containing the stmn1 3'untranslated region. 20407606_2 this mir-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 . 20407606_4 we also confirmed by ectopic expression and sirna knockdown, the ability of muc1 to promote cell invasion which can be reversed by mir-145. of interest, suppression of muc1 by mir-145 causes a reduction of -beta-catenin as well as the oncogenic cadherin-11. 26199425_1 these results indicated that mir-570 and mir-378 regulate cyp2e1 expression in haplotype-dependent and haplotype-independent manners, respectively. 26199425_2 when mir-570 was transfected into the hek/2e1 cells, the cyp2e1 protein level was significantly decreased , whereas this did not occur in the hek/2e1 cells . 24705038_1 mir-124 directly targets tlr signaling tlr6, myd88, traf7 and tnf-alpha. 21548134_1 traf6 and irak1 are bona fide targets of mir-146a. 21548134_2 consistent with our proposed model , analysis of mir-146a-搉ull bmdms revealed a marked increase in traf6 and irak1 protein levels in comparison with wt cells . 26754670_1 forced expression of mir-208a promoted cell proliferation and induced radioresistance via targeting p21 with a corresponding activation of the akt/mtor pathway in lung cancer cells, whereas down-regulation of mir-208a resulted in the opposite effects. 26754670_2 the present study provides evidence that mir-208a can affect the proliferation and radiosensitivity of human lung cancer cells by targeting p21 and can be transported by exosomes. 26754670_3 these results indicated p21 as a target of mir-208a for its regulatory function in lung cancer. 26754670_4 among the differentially expressed mirnas, mir-208a promoted lung cancer cell proliferation and decreased cell apoptosis by targeting p21 and akt/mtor pathway. 22472569_1 mir-145 target vegf by interacting with 3'utr. 22472569_2 on the basis of these results, we performed the luciferase assay and verified that mir-145 could down-regulate vegf at the translational level by partially binding to vegf 3' untranslated region . 22472569_4 these data demonstrated that mir-145-regulated vegf expression at the translational level by interacting with the 3'utr of vegf. the results showed that co-transfection with mir-145 and pmir-report-3' utr resulted in a significant decline of luciferase activity, which indicated that vegf is a direct targetgene of mir-145. 22472569_5 the expression of vegf may be negatively regulated by mir-145 on the translational level through binding to vegf 3' utr partially. 20428827_1 the study demonstrated that cisplatin induces k562 cells to apoptosis by reducing mir-106 which up-regulates rb1 or by inhibiting mir-150 which increases p53 expression. 25493074_1 mir-100 transfection reduces expression of baz2a, mtor and smarca5 mrna and protein in bc cell lines. 26390174_1 both mir-185-3p and mir-324-3p can target 3'-utr of smad7 and modulate growth and apoptosis of npc cells. 25666090_2 restoration of hbp1 abolished the effect of mir-155 on os cells. 25666090_3 the above data showed that hbp1 is an authentic target of mir-155 in os cells. 25666090_4 the data demonstrated that sihbp1-caused hbp1 suppression was able to prevent u2os cells from the effect of mir-155 downregulation on os cell proliferation and cell cycle progression . 26089393_2 we showed that biotin-tagged and thiouridine-labelled mir-9 can efficiently pull-out xrn2, srsf1, stau1, lsm14a and eif5 compared to non-thiouridine-labelled controls, validating them as direct mir-9 targets . 26089393_4 using western blots, we further confirmed that mir-9 efficiently regulates xrn2, srsf1 and stau1 at a translational level while non-target prdm5 did not show substantial change relative to control . 26487644_1 taken together, our results demonstrated that c-myc was a direct target of mir-320b in crc cells. 22898998_1 dnmt1 was identified as a direct target of mirna-140. 22898998_2 mirna-140 acts as a liver tumor suppressor by controlling nf-kappab activity via directly targeting dnmt1 expression. 22898998_3 our study identified dnmt1 as a critical target of mirna-140. 26800338_1 in the presentstudy, we investigated the role of mir-382 in crc and identified the regulation of nr2f2 by mir-382. 26800338_2 the direct bindingof mir-382 to the 3 ' untranslated region of nr2f2 was confirmed using a luciferase reporter gene assay. 26800338_3 the results suggest that mir-382 plays an important role in cell proliferation, invasion, and migration by regulating its target gene nr2f2 in human crc. in summary, the present study identifies the regulatory link between mir-382 and nr2f2 and describes a potential mechanism underlying nr2f2 dysregulation and its contribution to crc progression. 23615404_1 results showed that mir-145 significantly repressed the luciferase activity of reporter vector harboring wild-type 3'-utr of oct4, whereas mutation of the putative mir-145 binding site in oct4 3'-utr abrogated the inhibitory effect of mir-145. 23615404_2 western blotting analyses further confirmed that the oct4 protein level was markedly decreased upon mir-145 transfection. 23615404_3 however, mir-145 had no effect on the mrna level of oct4 as determined by qrt-pcr, suggesting that mir-145 regulates oct4 expression via translational inhibition in hcc cells. 17641203_1 we show that hcmv-mir-ul112 specifically down-regulates micb expression during viral infection. 26045777_1 thus, our results confirmed that, in mouse cornea, cx43 was the direct target of mir-206. 26045777_2 the result showed that the protein of cx43 was dramatically up-regulated while mir-206 was suppressed by mir-206-i ; further confirming that cx43 was directly regulated by mir-206 in mouse cornea. 26887050_1 the apoptosis regulator bim was identified as a direct target of mir-138, and its silencing mediated the induced tmz resistance phenotype. 26887050_3 immunoblot analysis for expression of the mir-138 target sox4 in ln-229 cells confirmed the biological activity of mir-138 inhibition . 26887050_4 conversely, the overexpression of mir-138 decreased sox4 levels by 40% in ln-308 cells selected for their low baseline mir-138 expression. 26887050_5 luciferase reporter assays assessing mir-138 binding to the bim-3'-utr region confirmed bim as a direct target of mir-138. 26887050_6 figure 4: bim downregulation via mir-138 confers tmz resistance to glioma cells. 19549910_1 two mirnas, mir-15a and mir-16, which are located at chromosome 13q14, have been implicated in cell cycle control and apoptosis, but little information is available about their role in solid tumors. 19549910_3 here, we show that mir-15a/mir-16 are frequently deleted or down-regulated in squamous cell carcinomas and adenocarcinomas of the lung. in these tumors, expression of mir-15a/mir-16 inversely correlates with the expression of cyclin d1. 19360360_3 subsequently, rtkn is identified as a potential mir-145 target by bioinformatics. 19360360_4 using reporter constructs, we show that the rtkn 3' untranslated region carries the directly binding site of mir-145. 19360360_5 additionally, overexpression of mir-145 in mcf-7 reduces rtkn protein expression as well as mrna level. 19360360_7 taken together, we propose that loss of mir-145 may provide a selective growth advantage for mcf-7 by targeting rtkn. 18945769_1 thus, the reporter assays demonstrated that targets such as pu.1, cebpe, hivep2, bcl2l13, and pdcd6 can be negatively regulated by both gga-mir-155 and mdv-1-mir-m4. 26351562_2 ovexpression of mir- 125b also inhibited pth1r downstream targets such as rankl and il- 8 expression, whereas knockdown of this mirna increased rankl and il- 8 expression , further indicating that pth1r is a target of mir- 125b in gct cells. 26351562_3 here, pth1r as a direct target of mir- 125b was further confirmed in luciferase activity assays and mir- 125b-mediated pthr1 expression analysis. 25174704_1 mir-195 overexpression resulted in a reduction in cell proliferation. in addition, the overexpression of mir-195 in hcc cells induced g1 phase cell cycle arrest and promoted apoptosis. 25174704_2 furthermore, wnt3a was demonstrated to be directly targeted by mir-195. 25174704_3 these findings suggest that mir-195 is key in regulating cell proliferation, cell cycle and apoptosis through targeting wnt3a. in addition, overexpression of mir-195 may be a potential therapeutic strategy in the treatment of hcc. 26097868_1 to further confirm nrp1 as a mir-148a target, mir-148a binding site in the nrp1 3'-utr region was mutated by site directed mutagenesis as shown in figure 5b. the cells expressing nrp1 3'-utr mutant construct failed to show reduction in the luciferase activity in the presence of mir-148a. 26097868_3 therefore, mir-148a appears to target only the full length nrp1 isoform and not the 80 kda isoform as it lacks the 3'-utr. 18505919_1 the mir-34a and mir-34c mimics showed dramatic growth inhibition in cell lines with 1p36 hemizygous deletion. 18505919_4 expression of mir-34a was also decreased in primary tumors with 1p36 deletion , but no mutations were discovered in resequencing of the mir-34a locus in 30 neuroblastoma cell lines. 18505919_5 bcl2 and mycn were identified as mir-34a targets and likely mediators of the tumor suppressor phenotypic effect. 16166379_1 when sgrs rna was induced, it resulted in the destabilization of ptsg mrna.the 16166379_2 degradation of ptsg mrna mediated by sgrs no longer occurred in a newly constructed strain totally lacking the hfq gene. 16166379_3 the sgrs level in the hfq strain was significantly decreased as presumed because of its reduced stability in the absence of hfq as observed in other hfq-binding small rnas.the 16166379_4 finding that hfq is tightly associated with rnase e strongly suggest that sgrs associates with rnase e through hfq. 23831330_1 it was further demonstrated in vitro that mir-30a was able to bind the 3- untranslated region of snai1 and overexpression of mir-30a blocked tgf--beta1-搃nduced up-regulation of snai1 and, therefore, inhibited emt and collagen expression. 23831330_2 as shown in figure 5b, overexpression of mir-30a in hmrsv5 cells attenuated the activity of wild-type snai1 3- utr reporter to 35%, which was not found in the mutant snai1 3- utr reporter. 23831330_3 interestingly, western blot analysis and real-time pcr showed that mir-30a overexpression dramatically down-regulated the protein level of snai1 , but did not alter its mrna level , demonstrating that mir-30a repressed the translation of snai1, but did not induce degradation of snai1 mrna. 23902770_1 because fccgammar clustering induces sflt-1 and because mir-181a was shown to negatively regulate sflt-1, we asked whether mir-181a was basally expressed in monocytes but down-regulated upon fcgammar activation. 23902770_2 figure 6. fcgammar clustering down-regulates mir181a while up-regulating sflt-1 transcription and protein synthesis. 18710938_1 these data are consistent with cyclin d1 protein and mrna expression patterns in differentiating mescs and with cyclin d1 being a target of mir-302 translational repression.//cyclin 18710938_2 d1 protein was significantly diminished in cells transfected with pre-mir-302a compared to its level in cells transfected with the negative control pre-mir, while cyclin d1 mrna was expressed at the same level in cells transfected with pre-mir-302a and negative control pre-mir.//the 18710938_3 cdk4 protein levels were increased in response to the inhibition of mir-302 in hescs , suggesting that cdk4 is also a target of mir-302. 18710938_4 additionally, the transfection of pre-mir-302a into hela cells caused the cdk4 protein levels to decrease , demonstrating that cdk4 is a target of mir-302 even in a heterologous system.these 18710938_5 data strongly suggest that mir-302a, -b, -c, and -d translationally repress cyclin d1 in hescs. 25337211_2 meanwhile mir-29b could induce apoptosis of mg63. 25337211_3 besides, mir-29b directly targets vegf and over-expression of mir-29b led to down-regulation of vegf protein level. 22210864_2 therefore, we performed 3'-utr reporter assays for mir-1 interference with translation using reporter constructs containing wild-type and mutant 3'-utrs of fn1, lasp1 and ptma. 22210864_3 xpo6 and notch3 have previously been shown to be a direct targetby mir-1 or mir-206. 22210864_4 the findings indicate that some of the mir-1 phenotypes in prostate cancer cells could be mediated by mir-1-induced disturbances of the actin filament network by directly targeting expression of fn1, lasp1 and xpo6, among other candidate transcripts that encode actin binding partners. 22210864_5 we found that mir-1 induces re-localization of lasp1 from the nucleus into the cytoplasm , which could be a compensatory process following lasp-1 down-regulation by mir-1. 23876508_1 mir-320a negatively regulates the expression of smar1 by directly binding to its 3'utr. in response to mild dna damage, mir-320a expression is decreased resulting in enhanced expression of smar1 protein, which in turn, reduces its targets, bax and puma inhibiting apoptosis. 21273305_1 we found that mir-539 and mir-381 are down-regulated by kit signaling and they repressed mitf expression through conserved mirna binding sites in the mitf 3'-untranslated region. 21273305_2 taken together, these results are consistent with the conclusion that the 3'-utr of mitf is specifically regulated by mir-539 and mir-381. 21273305_3 figure 7 mir-381 and mir-539 targetthe 3'-utr of mitf. 26548724_1 bioinformatics analysis revealed that mir-326 had a putative binding site within the 3'-untranslated region of nsbp1. 26548724_3 these results indicated that mir-326 could target the 3'-utr of nsbp1 and repress its expression in nsclc cells. 21145505_1 transfection experiments indicated that mirna-17 and mirna-20a directly repressed isl1 and tbx1. 22781587_4 this confirms that the expression of ghr is regulated by let-7b, and that the let-7b targetis located in the region of the ghr 3'-utr mutation. 22431749_1 in this paper, we report that a star strand mirna, mir-30c-2* , is induced by the protein kinase rna activated-搇ike er kinase pathway of the upr and governs expression of xbp1 , a key transcription factor that augments secretory capacity and promotes cell survival in the adaptive upr. 22431749_2 therefore, mir-30c-2* is functionally competent and recognizes the predicted cognate xbp1 3' utr target site in a sequence-specific manner. 22431749_3 these data establish that mir-30c-2* has the capacity to limit induction of xbp1 mrna, xbp1 protein, and xbp1-dependent target genes. 25984739_1 moreover, our results showed that key signal molecular traf6 is a target of mir-194, overexpression of mir-194 directly decreased traf6 expression and attenuated the release of proinflammatory cytokine tnf-alpha in pa-activated monocyte thp-1. 25984739_2 we conclude that mir-194 negatively regulates the tlr4 signal pathway which is activated by pa through directly negative traf6 expression. 25984739_3 as shown in figure 2e, mir-194 downregulated traf6 protein expression, while mir-194 inhibitor upregulated traf6 . 25984739_4 all of these results indicated that mir-194 directly target traf6. 26182877_1 mir-3178 regulates angiogenesis of hcc tecs, and egr3 is the functional target of mir-3178. 26182877_2 the results indicate the silencing effect of mir-3178 on egr3 mrna. 22167321_1 we demonstrate that mir-146a, mir-99b and mir-205, induced in hcc1937 brca1-expressing cells, bindand regulate traf2 gene. 22167321_2 collectively, these luciferase and western blot results showed that mir-146a, mir-99b and mir-205 act as negative regulators of traf2 expression. 22167321_3 we have identified traf2 as a novel targetgene for mir-146, mir-99 and mir-205 and shown that these mirnas are sufficient to modulate nf-jb pathway activity in breast cancer cells. 26518362_1 interestingly, there was no significant change in luciferase activity when mutant utr was co-transfected with mir-4516, suggesting that alteration of luciferase activity was because of direct binding of mir-4516 to the predicted binding sites on the ube2n 3'utr. 26614992_1 mir-577 in hcc group had a significant negative correlation relationship with the expression of downstream target of b -catenin . 26614992_2 mir-577 may inhibit the hcc cell growth through down-regulating the expression of b -catenin. 26614992_3 therefore, the negative regulation of mir-577 on b -catenin expression, which is confirmed by the present study, may have the important clinical value to ameliorate the treatment and prognosis of sorafenib resistant patients. 26402653_1 further studies determined that p21cip1/waf1 was the direct target of mir-423-3p, and that ectopic expression of p21cip1/wf1 totally rescued the effect of mir-423-3p on crc growth. 26402653_2 these data indicated that mir-423-3p inhibited the p21cip1/waf1 3'-utr by direct binding to site1. 26402653_3 these data suggested that mir-423-3p directly regulated p21cip1/waf1 expression in crc. 26402653_4 our current study showed that p21cip1/waf1 was the direct target of mir-423-3p in inhibition of crc occurrence. 18684319_1 utilizing human cell lines, we demonstrate that mirnas hsa-mir-106a and hsa-mir-520c bindto their predicted targetsequences in the app 3'utr and negatively regulate reporter gene expression. 18684319_2 over-expression of these mirnas, but not control mirnas,result utilizing human cell lines, we demonstrate that mirnas hsa-mir-106a and hsa-mir-520c bind to their predicted targetsequences in the app 3'utr and negatively regulate reporter gene expression. 18684319_3 over-expression of these mirnas, but not control mirnas,results in translational repression of app mrna and significantly reduces app protein levels. 18684319_4 we observed that mir-520c over-expression significantly decreased luciferase activity when the putative mir-106a targetsite was included in the reporter compared to either a reporter lacking the putative targetsite or a reporter carrying a seed-region mutant of the putative mir-106a targetsite . 19308264_1 in a screening of mb cell lines, the mirna mir-199b-5p was seen to be a regulator of the notch pathway through its targeting of the transcription factor hes1. down-regulation of hes1 expression by mir-199b-5p negatively regulates the proliferation rate and anchorage-independent growth of mb cells. 19308264_2 mir-199b-5p over-expression blocks expression of several cancer stem-cell genes, impairs the engrafting potential of mb cells in the cerebellum of athymic/nude mice, and of particular interest, decreases the mb stem-cell-like subpopulation of cells. in our analysis of 61 patients with mb, the expression of mir-199b-5p in the non-metastatic cases was significantly higher than in the metastatic cases . 19308264_4 these data showing the down-regulation of mir-199b-5p in metastatic mbs suggest a potential silencing mechanism through epigenetic or genetic alterations. 19308264_7 infection with mb cells in an induced xenograft model in the mouse cerebellum and the use of an adenovirus carrying mir-199b-5p indicate a clinical benefit through this negative influence of mir-199b-5p on tumor growth and on the subset of mb stem-cell-like cells, providing further proof of concept. 25878056_1 these explorations led to the identification of candidate targets of mir-199a-5p: wnt signaling, including fzd4 and wnt2 . 25878056_4 to verify that fzd4 and wnt2 are indeed repressed post transcriptionally by mir-199a-5p, we determined the effect of mir-199a-5p on protein expression. 25878056_5 the results of western blot analysis indicated that mir-199a-5p markedly lowered the levels of fzd4 and wnt2 proteins in mc3t3-e1. 25878056_6 the results indicated that mir-199a-5p significantly decreased fzd4 and wnt2 protein expression,and amo-199a-5p increased it. 26102062_1 collectively, our results suggested that prlr is a direct target gene of mir-135a, mir-135a is a novel regulator of prlr, and it might play an essential role in the regulation of animal mammary gland development and lactation. 26102062_2 these results indicated that mir-135a could directly target the 3'utr sequences of prlr; prlr is a direct target gene of mir-135a. 26102062_3 these results suggested that prlr expression is directly targeted and regulated by mir-135a, mir-135a is a negatively regulator of prlr. 26102062_4 this is the first study to show that prlr is negatively regulated by mir-135a at the post-transcriptional level through its target site within the 3'utr . 23579070_1 these suggest that mir-135a targets irs2 levels by binding to its 3'utr and this interaction regulates skeletal muscle insulin signaling. 23579070_2 these results imply towards a specific interaction between mir-135a and irs2 to regulate endogenous irs2 levels. 23579070_3 all these suggest that mir-135a decreases irs2 levels by binding to its 3'-utr. 20844033_1 we further analyzed changes in mir-126, an ec-specific mirna that regulates vascular integrity by suppressing spred1 and pik3r2 mrnas.the 21982769_1 mir-146a decreased the sensitivity to ifn-alpha through the suppression of apoptosis. 21982769_2 further experiments showed that mir-146a-related resistance to ifn-alpha was mediated through smad4. 22040413_1 then western blotting analysis and luciferase reporter assay were measured to determine whether fak was indeed regulated by mir-7. 22040413_2 these indicate that mir-7 modulates fak expression via its 3'-utr. 22040413_3 meanwhile, pearson's correlation analysis showed that mir-7 expression was negatively correlated with fak expression . 22040413_4 figure 2. mir-7 directly target the 3'-utr of fak mrna in glioma cell line. 21526342_1 taken together, these data imply that mir-126-3p may attenuate the expression of pgr by directly targeting the 3' utr of pgr. 21526342_2 fig. 1 mir-126-3p target 3' utr of pgr mrna. in conclusion, pgr gene confirmed mir-126-3p targetgenes through luciferase activity and western blotting. 21526342_3 and mir-126-3p could also inhibit proliferation of mousemammary epithelial cells and expression of -beta-casein , and down-regulate pgr protein . 26165303_1 luciferase reporter was employed to confirm the binding sites in 3'utr region of celf2 for mir-95-3p. 26165303_2 the correlation between expression of celf2 and mir-95-3p was determined by western blotting and qrt-pcr both in cell lines and human samples. 26165303_3 results showed celf2 was a direct target of mir-95-3p and expression levels of celf2 and mir-95-3p were negatively correlated. 26165303_4 finally, celf2 largely abrogated the effects of mir-95-3p on proliferation, invasion and apoptosis of glioma cells in rescue experiments, which verified the role of celf2 in mir-95-3p regulating glioma biological behavior. 26165303_5 in conclusion, our data suggest the expression level of mir-95-3p is positively related to glioma grade and downregulation of mir-95-3p affects proliferation, invasion and apoptosis of glioma cells by targeting celf2. 26165303_6 we identified mir-95-3p as a putative therapeutic target and celf2 as a potential tumor suppressor. 26165303_7 based on the above, we proved that mir-95-3p suppresses celf2 gene expression by regulating 3'utr at the post-transcription level. 26314959_1 notably, we identified that overexpression of mir-625-3p inhibited the expression of scai, while depletion of mir-625-3p increased scai level, suggesting that scai could be a target of mir-625-3p. 26314959_2 our findings demonstrated that mir-625-3p could promote cell migration and invasion through inhibition of scai and its target e-cadherin. 26314959_3 here, our data suggest that mir-625-3p inhibited scai and led to increased migration and invasion in crc cells. 26648817_1 mir-15b and mir-219-5p was predicted to induce hematopoietic differentiation due to targeting sall4 in different levels. 26648817_2 we hypothesized hsa-mir-15b and hsa-mir-219-5p have potential for targeting sall4. 26648817_3 as predicted by mirbase, 3' utr of sall4 had complementary sequence for has-mir-15b and has-mir-219-5p seed sequence. 26648817_4 these results indicate that down-regulation of hsa-mir-15b and consequently up regulation of sall4 lead to in the expansion of primary hscs. 26648817_5 based on our analyses, mir-15b targets sall4 mrna and reduced its expression in hscs. 22020437_1 escs over-expressing mir-34a, mir-34b, or mir-34c for 48 hours had decreased nanog, sox2 and n-myc protein levels , but unaltered mrna abundance . 24824743_1 taken together, these results suggest that mir-218 regulates mitf expression by directly binding its gene at 3'-utr. in our study, a novel function and mechanism of mir-218 was found in its targeting of mitf 3'-utr and suppression of melanogenesis in a normal melanocyte model of murine melan-a cells. 24824743_2 a luciferase activity assay demonstrated the direct binding of mir-218 to the 3'-utr of the mitf gene . 26394192_1 mir-340 directly targets the 3'-utr of hmgn5. 26394192_2 these results indicate that mir-340 directly targeted the 3'-utr of hmgn5. 26394192_3 the data further confirmed that mir-340 targeted and regulated hmgn5. 26143374_2 eif4e expression was dramatically reduced after transfection with mir-206 . 26258411_1 altogether, these data reveal that mir-373 directly suppresses the translation of itga2 by binding to the itga2-3'-utr. 24039891_1 to further evaluate the putative differential targeting of the mir-375 5- -isomirs, we selected the following three genes: mtpn, which regulates insulin secretion, is a known target of the 5- -reference mir-375 , but is not predicted to be targeted by the 5- -shifted isoforms; atp6v0c, which mediates glucose-sensitive intracellular vesicular transport and is predicted to be preferentially targeted by the 5- -shifted isoform mir-375+1; and cdc42, which is essential for the second phase of insulin secretion and is predicted to be preferentially targeted by the 5- -shifted isoform mir-375-1. 26117405_1 using microarray and bioinformatics analyses, pgc-1alpha was identified as a common target gene of mir-19b-3p, mir-221-3p and mir-222-3p, which are mainly located in the intima of atherosclerotic vessels. in vitro induction of mir-19b-3p, mir-221-3p and mir-222-3p by the inflammatory cytokines tnfalpha and ifngamma may affect pgc-1alpha protein production and consequently result in mitochondrial dysfunction in human aortic endothelial cells . 26117405_2 taken together, these results suggest that the drastic increase in the expression levels of micrornas mir-19b-3p, mir-221-3p and mir-222-3p in atherosclerotic vessels modulates pgc-1alpha protein production via targeting the 3'-utr of pgc-1alpha. 22438559_1 fig 3 the 8-hpi network shows a number of deregulated mirnas and their predicted targets, including mir-766, that is consistently upregulated throughout infection with h1n1. 20819078_1 furthermore, as shown by quantitative real-time rt-pcr and western blotting , ectopic transfection of mir-7 reduced the level of igf1r at both the mrna and protein levels. 20819078_2 knockdown of mir-7 led to increases in both igf1r mrna and protein. 20819078_3 thus these results demonstrated that mir-7 regulates igf1r expression by directly targeting the 3'-utr of the igf1r mrna. 20819078_4 together with the observed mir-7 effects on igf1-induced akt activation, these results suggest that mir-7 regulates tscc cell growth, at least in part, by targeting igf1r. 26354435_1 down-regulation of mir-125b, which targets gab2, mediates par 2 -induced cancer cell migration. 26354435_2 moreover, grb associated-binding protein 2 was identified as a novel target gene of mir-125b and it mediated par 2 -induced cell migration. 26354435_3 all these results suggest that mir125b partially regulates gab2 expression through the binding site within 3'-utr of gab2 mrna. 26354435_4 gab2 was identified as a novel target of mir-125b in the current study. 17761882_1 mir-133b regulates the maturation and function of midbrain dns within a negative feedback circuit that includes the paired-like homeodomain transcription factor pitx3 20736237_2 we tested whether mir-27b is able to regulate mef2c by generating luciferase reporter constructs with wild-type and mir-27 "seed" sequence-mutated mef2c 3'-utrs. in addition, we tested whether other micrornas, which have no predicted target site on the mef2c 3'-utr, might affect mef2c. 20736237_3 overexpression of mir-125a or mir-219 does not modify mef2c transcript levels . 20736237_4 thus, our data demonstrate a role for mir-27b regulating mef2c expression levels in myogenic cells. 23086751_1 restoration of mir-30b or mir-30c expression during kaposi sarcoma herpesvirus infection attenuated viral induction of dll4. 23086751_2 together these results demonstrate that the highly conserved molecular targeting of dll4 by the mir-30 family regulates angiogenesis. 23086751_3 figure 2 mir-30b and mir-30c regulate dll4. 23086751_4 taken together, these data indicate that the mir-30 family regulates endogenous dll4. 23086751_5 these data indicate that mir-30 influences the expression of dll4 in endothelial cells by targeting a predicted site within its 3'-utr. 23316333_1 tsp-1 is the main target of mir-467 and the main mediator in regulation of angiogenesis. 23316333_2 the experiments with the constructs, in which the binding site for mir-467 was mutated, demonstrated that the direct binding of mir-467 to the 3- utr of tsp-1 is required for the translational silencing of tsp-1 mrna in response to high glucose. 23316333_3 mutation of the mir-467 binding site in tsp-1 3- utr or mir-467 inhibitor relieved the translational silencing and restored tsp-1 production. 26604785_1 mir-328 and ptprj mrna expression levels were markedly upregulated and downregulated in hcc tissues. 26604785_2 the upregulation of mir-328 in hcc tissues was significantly correlated with the downregulation of ptprj mrna in hcc tissues 26092503_2 the time courses of expressions of mir-320 and phospho-hsp20 in the spinal cord, after the transient ischemia, indicated that expression of phospho-hsp20 was negatively correlated with expression of mir-320. 26092503_3 transfection of antagomir-320 significantly reduced expression of mir-320 in the spinal cord and dramatically up-regulated expression of phospho-hsp20. 20549700_1 to unravel the mechanism by which mir-125b restrains g1/s transition, we examined possible cell cycle-related target of e2f3, cyclin a2, cyclin e1, cyclin d1, cdc6 and cdk6. 20549700_2 we found that induction of mir-125b inhibited cyclin a2 at the mrna level in both t24 and 5637 cell lines, whereas cyclin e1, cyclin d1, cdc6 and cdk6 were almost unchanged compared with nc-transfectants . 24980823_1 mir-143 acts as a tumor suppressor by targeting n-ras and enhances temozolomide-induced apoptosis in glioma. 25569036_1 expression of mir-708 results in decreased ovarian cancer cell migration/invasion and metastasis mainly through targeting rap1b. 25569036_2 although our data only reflected mrna levels, and some genes might be affected translationally, we decided to focus on rap1b as the major target of mir-708 in ovarian cancer. 25569036_3 co-expression of anti-mir-708 fully reversed mir-708-mediated inhibition, indicating that rap1b is a direct downstream target of mir-708. 21642433_3 we found that mir-10b reduced the activity of a luciferase reporter gene fused to the wild-type 3'-utr of hoxd10 , but had no effect on the 3'-utr of nrp2 or nr4a3 . 21642433_4 to test the binding specificity of mir-10b, specific base pair mutations on the 3'-utr of hoxd10 mrna was performed using the site-directed mutagenesis method followed by co-transfection with mir-10b. 21642433_5 this suggested that mir-10b specifically targeted the 3'-utr of hoxd10 mrna . in addition, we observed significant expression of the luciferase reporter gene fused to the 3'-utr of hoxd10 after anti-mir-10b treatment . 21642433_6 to determine whether mir-10b could disrupt endogenous hoxd10 expression in endothelial cells, cell lysates from mir-10b-transfected or vector control hmec-1 cells were analyzed. 21642433_7 although mir-10b slightly inhibited mrna expression of hoxd10 in hmec-1 cells, it might impair hoxd10 expression through translational inhibition. 21642433_8 indeed, expression of the hoxd10 protein was significantly reduced in cells that overexpressed mir-10b . 21642433_9 these results suggest that hoxd10 is indeed an important functional target of mir-10b in hmec-1. 21642433_10 our results showed that inhibition of mir-10b expression and up-regulation of hoxd10 expression were implicated in this process. 26886754_1 in this study, we first investigated the effects of atorvastatin on mir-126 and its target gene, i.e., vascular cell adhesion molecule-1 in apolipoprotein e-knockout mice with carotid atherosclerotic plaque in vivo. 26886754_2 these data indicated that the down-regulated expression of mir-126 and the up-regulated expression of vcam-1 were involved in atherosclerotic formation and that treatment with atorvastatin regulated the level of mir-126 mrna expression . 22728051_1 loss of mir-21 also increased cleavage of caspase-3 and increased phosphorylation of elongation factor-2 in both cell lines. 22728051_2 our studies indicate regulation of pdcd-4 expression is not a primary mir-21 function in leiomyomas, but instead mir-21 is able to impact cellular apoptosis and translation, through unknown targets, in a manner consistent with its involvement in the pathophysiology of uterine fibroids. 22580051_1 therefore, we concluded that the inserted fragment of igf-ir was the target of mir-139. 23132946_1 furthermore, our studies demonstrate that pbx3 and meis1 are two direct targetgenes of mir-495, and forced expression of either of them can reverse the effects of mir-495 overexpression on inhibiting cell viability and promoting apoptosis of human mll-rearranged leukemic cells. 23132946_2 finally, our luciferase reporter and mutagenesis assays showed that mir-495 targeted the 3'-utr of both pbx3 and meis1 directly . 23132946_3 thus, several lines of evidence indicate that both pbx3 and meis1 are direct targetgenes of mir-495. 23132946_4 therefore, our data suggest that both pbx3 and meis1 are functionally important targetgenes of mir-495 in mll-rearranged leukemic cells. 25424744_1 to validate the interactions between mir-125b and hottip, luciferase reporter assay was performed with wild-type and seed-sequence mutated mir-125b target sequences of hottip. 25424744_2 when mir-125b precursor was cotransfected with the putative mir-125b target sequence of hottip in bel7402 cells, the luciferase signal was significantly suppressed as compared to the empty vector control, while the suppressive effect was significantly attenuated when the putative binding site was mutated. 26850595_1 abcb1 was a direct downstream target of mir-873 and downregulated by binding of mir-873 to its 3'-utr. 26850595_2 the predicted seed region in the 3'-utr of abcb1 showed that abcb1 was a direct target of mir-873. 19131573_1 mutations in the predicted mir-124a seed region abolished this repression, thus strongly indicating that mir124 binds the predicted targetsite in the ratgr mrna. 19131573_2 interestingly, mir-124a up-regulation is associated with a 70% reduction of gr protein , suggesting an interaction between endogenous mir-124a and gr mrna. 26679605_1 furthermore, mir-186 induced downregulation of jagged1 protein expression by directly targeting its 3 ' -untranslated region . 26679605_3 based on the collective results, we propose that mir-186 regulates protein expression of jagged1 by directly targeting its 3 ' utr region. 26324325_1 using bioinformatic analyses, we found that mucin 1 was a potential target for mir-1291. 26324325_2 luciferase assays were performed to reveal that mir-1291 inhibited muc1 expression by targeting the seed region of muc1 3'-untranslated region . 26324325_3 we also found that the expression of muc1 lacking in 3'utr abrogated the anti-invasion and pro-apoptosis function of mir-1291. 26324325_4 our results demonstrated the importance of mir-1291 in targeting muc1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for escc. 26324325_5 these results indicated that mir-1291 negatively regulated muc1 expression by directly binding to the 3'utr seed region in escc. 15210934_1 as in e. coli, induction of the prrf srnas leads to the rapid loss of mrnas for sodb , sdh , and a gene encoding a bacterioferritin. 15210934_2 thus, the prrf srnas are the functional homologs of ryhb srna. 21857646_1 we identify camta1 as an mir-9/9 and mir-17 target indeed, mir-9 inhibition effects on colony formation were rescued by camta1 depletion. 21857646_2 increased firefly activity was not observed, when reporters with mutated mir-9 or mir-9* bindsg sites were transfected. 21857646_3 furthermore, endogenous camta1 mrna as well as protein levels were elevated, when mir-9 or mir-9* was inhibited . of note, protein levels were much stronger increased than mrna levels, suggesting that mir-9/9* may preferentially inhibit camta1 translation. 21857646_4 we also observed a significant rescue of mir-9* inhibition, although not as strong as observed for mir-9. 21857646_5 indeed, overexpression of camta1 reduced the number of cd133+ cells, suggesting that the mir-9/9* effect is at least in part due to camta1 inhibition . 21857646_6 strikingly, inhibition of mir-9/9* or mir-17 increased nppa and npr-a expression presumably by inducing camta1 expression. 21857646_7 taken together, we have found that mir-9/9* and mir-17 regulate the expression of the novel tumour suppressor camta1 in cd133+ glioblastoma cells and camta1 itself stimulates the expression of the anti-proliferative peptide nppa. 20933503_1 real-time pcr analysis revealed that upregulation of mir-218 drastically repressed the expression level of mmp-9 mrna in u87mg and snb19 glioma cells , which indicated that mir-218 mediated the downregulation of mmp-9 at the transcriptional level. 20933503_2 taken together, our results suggest that upregulation of mir-218 reduces mmp-9 expression and inactivates nf-jb signaling. 22578566_3 however, by correcting the statistical analysis excluding double positive cases in which mir-205 and lamc1 were not expressed by the same cells , we observed a significant inverse correlation between mir-205 and lamc1 expression. 22578566_4 these data further indicate that mir-205 target lamc1 also in breast cancer tissues. 22578566_5 moreover, the mutation of the mir-205 binding site in lamc1 3'-utr prevented the downregulation of luciferase expression. 26898797_1 computational analysis predicted that mir-9 has two conserved binding sites in the 3'-utr of elavl1. 26898797_2 to further validate that elavl1 3'-utr is a direct target of mir-9, inhibition of mir-9 signi铿乧antly increased luciferase activity when compared to human cardiomyocytes transfected with mirna inhibitor negative control transfected cells. 26898797_3 these data evidently supports that mir-9 directly regulates elavl1. 26617805_1 the results showed that socs1 was a directly target gene of mir-19a. 26617805_2 we next investigated whether mir-19a could directly down-regulate socs1 expression in neuropathic pain models by western blotting analysis. 26617805_3 all these results implied that mir-19a might suppress socs1 in neuropathic pain models. 23764849_2 theseresults demonstrated the specific inhibition of akt3 expression by mir-29. 23764849_3 collectively, mir-29 inhibits myoblast proliferation by targeting the proliferation-associated genes akt3 and p85a. 26822763_3 these results indicate that mir-107 directly modulate cdk6 expression by binding mir-107 seed complementary site located in 3'-utr of cdk6. 26822763_4 furthermore, rt-pcr and western blot analysis showed that knockdown of neat1 in lscc cells led to increased level of mir-107 and decreased level of cdk6 protein . 24396870_1 hsa-mir-125b suppresses bladder cancer development by down-regulating oncogene sirt7 and oncogenic long non-coding rna malat1. 23322776_1 luciferase activity was reduced ~40% by mir-27a expression, but not by mir-24 expression , confirming that mir-27a indeed target the 3'-utr of gata-2 mrna in this cell type. 23322776_2 taken together, these results demonstrate that son knockdown up-regulates mir-27a, which, in turn, target the 3'-utr of gata-2 and down-regulates gata-2 expression. 23322776_3 our data revealed that reduction of the son level leads to depletion of the protein level of hematopoietic transcription factor gata-2 and this is mediated by mir-27a targeting gata-2 3'-utr. 23322776_4 we also observed that the 3'-utr of gata-2 with mir-27a binding site mutated was still affected, albeit less, by son sirna , which suggests other mirnas, in addition to mir-27a, regulated by the son level also targetthis 3'-utr to contribute to fine-tuning of the gata-2 protein level. 22362728_1 the dual-luciferase reporter gene assay results showed that ccnd3 was a direct target of mir-138. 22362728_2 these results indicated that mir-138 may be associated with ccnd3 and both of them may be involved in hcc tumorigenesis. 22362728_3 furthermore, transfection of mir-138 mimic decreased ccnd3 expression and transfection of mir-138 inhibitor increased ccnd3 expression in hepg2 cells at protein but not mrna level , suggesting that ccnd3 expression could be inhibited by mir-138 at post-transcriptional level. 22362728_4 together, the results show that mir-138 could regulate the expression of endogenous human ccnd3 by directly targeting the 3' utr of ccnd3 mrna and human ccnd3 is a new target of mir-138. 22362728_5 these results indicate that ccnd3 is most likely involved in the induction of cell cycle arrest by mir-138. 22362728_6 our data suggest the frequently downregulated mir-138 can regulate ccnd3 and function as a tumor suppressor in hcc. 21448283_1 since mir-34a is a direct target of p53 in many pathways 11, we next used p53 sufficient and deficient cell line hct116 p53+/+ cells and hct116 p53-/- cells to study the possible relationship of mir-34a and p53 in radio-sensitivity. 21448283_3 these data indicate that mir-34a is positively correlated to cellular radio-sensitivity and the induction of mir-34a was in a p53 dependent manner. 26820394_1 these results confirmed that mir-1 and mir-214 mimic transfection downregulated pim1 expression in mesothelioma cells. 26820394_2 here we add mir-1, mir-214 and its prediction target pim1 gene as possible target of therapeutic potential in mesothelioma. 26820394_3 in addition, by transfecting mir-1 and mir-214 mimic to two cell lines, acc-meso-1, and crl-5915, we also found the downregulation of pim1 protein expression suggesting the role of mir-1, and mir-214 in inhibition of pim1 expression. 21584493_2 the results indicated that rasa1 and rac1, related to cardiac hypertrophy, or tgfb3 and col1a1, related to myocardial fibrosis, were significantly increased in the heart tissue of diabetic mice . 22681957_1 over-expression of mir-221/222 increased cell invasion, whereas knockdown of mir-221/222 decreased cell invasion via modulating the levels of the target, timp3. 22681957_2 the present data indicate that mir-221 and mir-222 directly regulate cell invasion by targeting timp3 and act as prognostic factors for glioma patients. 22681957_3 furthermore, knockdown of mir-221/222 decreased invasion capability, reduced tumor growth and up-regulated the expression of the target, timp3, whereas ectopic expression of mir-221/222 exhibited the opposite effects. 22681957_4 these data indicate that mir-221/222 can directly modulate timp3 expression by binding to the 3- utr of timp3 in gliomas. 26844630_1 in silico analysis predicted two putative mir-932 target sites locate in the cds region of dnlg2 instead of regular 3'-utr mirna binding sites. 26844630_2 employing luciferase reporter assay, we further proved that the mir-932 regulates expression of its host gene dnlg2 via the binding cds region of dnlg2. 26844630_3 consistently, we observed mir-932 downregulated expression of dnlg2 in s2 cell, and the repression of dnlg2 by mir-932 at both protein and rna level. 26844630_4 furthermore, we found cds-located site1 is dominant for regulating expression of host dnlg2 by mir-932. 26844630_5 these results support the idea that dnlg2 may be a bona fide target of its intronic mir-932. 26844630_6 our results showed that cds region of host dnlg2 could be directly targeted by mir-932 and the level of dnlg2 as well as its mrna were decreased by mir-932. 20110463_2 taken together, the above data suggest that mir-221 target icam-1 3'-utr, resulting in posttranscriptional suppression in cholangiocytes. 20110463_3 moreover, no significant change in icam-1 mrna levels was found between the control cells and cells treated with anti-mir-221 , suggesting that mir-221 does not induce icam-1 mrna degradation. 25234165_1 luciferase reporter assays demonstrated that mir-29b targeted psme4 that encodes the proteasome activator pa200. 25234165_2 taken together, our study identifies mir-29b replacements as the first-in-class mir-based pis that also disrupt the autophagy pathway and highlight their potential to synergistically enhance the antimyeloma effect of bortezomib. 26879375_1 in addition, mir-640 bound to the 3'-utr of hif1a mrna and then inhibited the expression of hif1a. 26879375_2 overall, these results indicated that hif1a is a target for mir-640 in huvecs and it may promote the process of angiogenesis in vitro. 21217645_1 we demonstrate herein that an microrna mir-605 is a new component in the p53 gene network, being transcriptionally activated by p53 and post-transcriptionally repressing mdm2. 21217645_2 these analyses suggest a possibility of mir-605 to regulate mdm2 expression at the post-transcriptional level on one hand and to be regulated in its own expression at the transcriptional level by p53 on the other hand. 21217645_3 figure 1 mdm2 as a target of mir-605 for post-transcriptional repression. 23098654_1 mir-24 resulted in the largest ldh release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes. 23098654_2 additionally, the mrna and protein levels of the pro-apoptotic gene, bcl2l11, were down-regulated by mir-24 overexpression and up-regulated by mir-24 deficiency. 23098654_3 the luciferase reporter assay confirmed bcl2l11 to be a target of mir-24. 26166764_1 the txndc5 protein level decreased in rasfs after transfection with mir-573 mimic , but increased with the mir-573 inhibitor . 26166764_2 this evidence indicates that mir-573 may modulate txndc5 expression at the translational level by binding to the 3'utr of txndc5 mrna 21538319_1 we demonstrated that mir-126 directly inhibits dnmt1 translation via interaction with its 3'-untranslated region, and that overexpression of mir-126 in cd4+ t cells can significantly reduce dnmt1 protein levels. 21538319_2 taken together, these data strongly suggest that mir-126 up-regulation contributes to the reduction of dnmt1 protein levels in sle cd4+ t cells. 21538319_3 igure 2. effect of mir-126 on dnmt1 expression in cd4+ t cells, and identification of dnmt1 as an mir-126 target three days after transfection with psilencer-mir-126, mir-126 transcripts were increased by 4.68-fold, while those of the unrelated mir-142-5p gene remained unchanged. 19281778_1 indeed, cox-2 protein expression was suppressed by the overexpression of mir-101a, and the luciferase activity of reporter constructs containing the cox-2 3'utr was also suppressed by mir-101a overexpression. 19281778_2 to determine the target of mir-101a in the mammary gland, we analyzed the relationship between mir-101a and cyclooxygenase-2 . 19281778_3 cox-2 protein expression slightly decreased by dip stimulation and additionally decreased after the depletion of dip, showing an inverse relationship with the expression pattern of mir-101a. 19281778_4 we then analyzed changes in cox-2 protein expression in response to the overexpression of mir-101a and found that cox-2 was clearly suppressed by mir-101a . 19281778_5 furthermore, overexpression of mir-101a significantly reduced the luciferase activity of constructs containing the cox-2 3' -utr when compared to those containing the gapdh 3' -utr . 25027394_1 further, mir-137 was found to increase expression of e-cadherin and cytokeratin, but suppress expression of n-cadherin and vimentin. 25027394_3 these results suggest a novel mechanism that mir-137 regulates emt and inhibits cell migration via twist1 downregulation. 25027394_4 therefore, mir-137 may function as anti-migration and anti-metastasis in gist and our study provides a potential approach for developing mir-137-based therapeutic strategy for gist. 26416661_1 furthermore, mir-25 expression was negatively correlated with the protein levels of rgs3 in nsclcs tissues , indicating the possible translation inhibition of rgs3 by mir-25. 26416661_2 this result suggested that mir-25 directly targeted rgs3. 26416661_3 these results indicated that rgs3 was the functional target of mir-25 in nsclcs cells. 26416661_4 these data suggested that the upregulated mir-25 in nsclcs enhances the cell proliferation but retards cell apoptosis via rgs3. 26567220_1 further investigation revealed that igf1r, insr, ccnd2 and ccne1 were directly targeted by mir-195 and mir-497 in myoblasts. 26567220_2 this result indicates that mir-195 and mir-497 target the insr gene. 26567220_3 more importantly, the present study identified igf1r and insr as new targets of mir-195 and mir-497 in c2c12 cells. 22531314_1 mir-409-3p inhibits ht1080 cell proliferation, vascularization and metastasis by targeting angiogenin. 22531314_2 overexpression of mir-409-3p in fibrosarcoma ht1080 cells resulted in decreased steady-state level of ang transcript and ang production which were achieved through direct binding of this mirna to the ang 3'utr. 22531314_3 these data indicated that mir-409-3p downregulate ang expression through binding to its 3'utr. 25209181_1 this may be explained by the fact that mir-204-5p increases in colorectal cancer cases in order to inhibit increased activity of lc3b-ii in autophagy and bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor. 21181092_1 the signal from a luciferase reporter was significantly decreased at one mir-133a targetsite at the 3'utr of gstp1,suggesting that mir-133a directly regulates gstp1. 21181092_2 this suggests that mir-133a regulates gstp1 expression by cleavage or translational inhibition. 21181092_3 figure 5. mir-133a regulates gstp1 expression in the sas cell line at the mrna and post-transcriptional level by targeting the 3'utr of gstp1 mrna. 26460960_1 suppression of vegf-c by mir-27b, mir-101 and mir-128 was investigated by luciferase assays, western blot and elisa. 26460960_2 figure 3 mir-27b, mir-101, or mir-128 directly down-regulates vegf-c expression through posttranscriptional repression in gastric cancer cells. 26460960_3 collectively, our data suggest vegf-c is down-regulated by mir-27b, mir-101, or mir-128. 26893637_2 thus, it was concluded that ccr5 is negatively regulated by mir-107 in cervical cancer cells. 24250812_1 based on the identification of complementary binding sites in mir-223 and igf-1r mrna, it is proposed that mir-223 acts as a local regulator of igf-1r. 24250812_3 addition, proliferation, apoptosis, and differentiation were assayed in these two hesc populations and were compared in the presence of exogenous mir-223 and mir-223 inhibitor. 24250812_4 inhibition of mir-223 was found to maintain the undifferentiated state of hescs, while addition of mir-223 induced differentiation. 26302771_1 fxyd6 was verified to be directly interacting with mir-137, and its subsequent upregulation reversed the inhibitory effect of mir-137 upregulation in osteosarcoma. 26302771_2 therefore, the experiment of luciferase assay confirmed that fxyd6 is the downstream target of mir-137. 26302771_3 taken together, our work of dual-luciferase assay and qrt-pcr demonstrated that fxyd6 was directly linked with mir-137 in human osteosarcoma. 25228695_1 the mir-152-mediated reduction of the 14-3-3-beta expression was accompanied by an up-regulation of bax protein expression resulting in a pro-apoptotic phenotype. 26698246_1 these results confirmed that mir-155 can directly target ubqln1 3'-utr and decrease it expression 19996288_2 real-time rt-pcr analysis detected a slight reduction of muc1 mrna in mir-145 cells compared with the vector control in mda-mb-231 or lm2-4142 cells, but this difference was not significant , suggesting that mir-145 silences muc1 mainly at the translational level. 19996288_3 experimental metastasis assays further supported the role of mir-145 in suppressing invasion and metastasis by targeting muc1. 19996288_4 for example, muc1 plus vector produced an average of 85 tumor nodules compared with 13 nodules from the muc1 plus mir-145 cells , similar to the invasion results. 19996288_5 these results suggest that mir-145 target muc1, which in turn causes downregulation of -beta-catenin, cyclin d1, and cadherin 11, leading to suppression of invasion and metastasis. 21770019_1 micrornas mir-16-1 and mir-15b have been reported to function as tumor suppressors and negative regulators of cell growth. 21770019_3 bcl2 and the bcl2-like anti-apoptotic proteins bcl2-associated athanogene 5 and bcl2-like 2 are targets of mir-16 and mir-15a . 20886540_1 similar to the data obtained from western blot analysis, ectopic expression of mir-125bm induced a markeddownregulation of p53, puma and bak1 . 20886540_2 taken together, these data strongly support that mir-125b down-regulates the expression of p53, puma and bak1 in cap cells. 20886540_3 taken together, these results provide experimental validation that the 3'-utrs of p53 and puma are target of mir-125b. 19133651_2 using both a luciferase reporter assay and western blot analysis, we showed that microrna-101 repressed the expression of v-fos fbj murine osteosarcoma viral oncogene homolog oncogene, a key component of the activator protein-1 transcription factor. 19133651_3 moreover, using a luciferase expression vector driven by seven copies of an ap-1 cis-element, we observed that microrna-101 expression inhibited phorbol 12-myristate 13-acetate -induced ap-1 activity. 19133651_6 conclusion: microrna-101, which is aberrantly expressed in hcc, could repress the expression of the fos oncogene. 18384814_1 nfib protein usually bindhe mir-21 promoter in hl-60 cells as a negative regulator and is swept off from the mir-21 promoter during pma-induced macrophage differentiation of hl-60. 18384814_2 the translational repression of nfib mrna by mir-21 accelerates clearance of nfib in parallel with the simultaneous mir-21-independent transcriptional repression of nfib after pma stimulation. 18384814_3 to further validate whether nfib transcript is directly targeted by mir-21, we inserted the nfib 3- utr downstream of the luciferase gene driven by tk promoter in a reporter plasmid and transfected the resultant reporter plasmid into the pa-1 cell line, which expresses only marginal endogenous mir-21 . 18384814_5 such mir-21-dependent reduction was never observed when a reporter plasmid that has mutation in the mirna recognition element for mir-21 was used instead . 22677435_1 the expression of ccnd1, ccnd2 and cdk6 was suppressed by mir-16 in hmscs. 22677435_2 cdk6, ccnd1, and ccnd2 were shown to be modulated by mir-16. 22677435_3 real-time pcr result revealed that cdk6, ccnd1 and ccnd2 mrna expressions were not changed significantly in the mir-16-modified hmscs . 22677435_4 however, western blot analysis showed that cdk6, ccnd1, and ccnd2 expressions were significantly inhibited in mir- 16-modified hmscs . 24790458_1 mir-519d binding sites on the 3' untranslated region of x-linked inhibitor of apoptosis protein .overexpression of mir-519d decreased xiap expression at both the protein and mrna levels. 26865454_1 we further demonstrated that bcl6 was the direct target gene of mir-144, and mir-144 suppressed the expression of bcl6 via binding the 3' untranslated region ofbcl6 mrna. 26865454_2 these results indicate that mir-144 and bcl6 expression were negatively correlated in dlbcl patients. 20551325_4 these data demonstrated that mir-29a negatively regulates endogenous levels of dkk1, kremen2, and sfrp2 protein during osteogenic differentiation in human cells. 20967756_1 microrna mir-141 that targets dlc-1 was accentuated in cells infected with hcv genotypes 1a, 1b, and 2a. 20967756_2 we present several lines of evidence that efficient hcv replication requires mir-141-mediated suppression of dlc-1. 20967756_3 an increase in mir-141 correlated with the inhibition of dlc-1 protein in hcv-infected cells. 20578129_1 our findings suggest that mir-152 is frequently down-regulated and regulates dnmt1 in hbv-related hcc. 17554199_1 differential regulation of micrornas by p53 revealed by massively parallel sequencing: mir-34a is a p53 target that induces apoptosis and g1-arrest. 22102818_2 interestingly, we found that bcg significantly upregulated mir146a in dcs as compared with h37rv-infected dcs . 22102818_3 furthermore, specific knock-down of mir146a expression dramatically upregulate both mrna and protein level of il-6 in bcg-infected dcs . 19008416_1 to examine whether mir-101 could regulate the 3'-utr of ezh2, we generated luciferase reporters encoding the normal, antisense, and mutated versions of the ezh2 3'utr. 19008416_2 overexpression of mir-101, but not mir-217 or control mirna decreased the activity of the luciferase reporter encoding the 3'-utr of ezh2 . 19008416_3 mir-101 regulation of the 3'utr of ezh2. 19008416_4 overexpression of mir-101, but not mir-217 or control mirna, decreased the activity of the luciferase reporter encoding the 3'-utr of ezh2 . 19008416_5 mir-101 overexpression also leads to repression of ezh2 tight binding partners in the prc2 complex: eed and, to a lesser extent, suz12. 19008416_7 4c displays a heatmap representation of matched samples in which mir-101 transcript, ezh2 transcript, mir-101-1 genomic loci and mir-101-2 genomic loci were monitored. 19008416_8 ezh2 transcript levels were inversely associated with mir-101 transcript levels across prostate cancer progression to metastasis . 26692953_1 further dual luciferase reporter assay showed that mir-1269 with gg genotype have a stronger binding ability with sox6. 26692953_2 we found that mir-1269 could directly bind with the 3'-utr region of sox6 which resulting in the decreased fluorescence activity of plasmid containing the wild type of the 3'-utr region of sox6 . 26692953_3 the results indicated that the existence of an allele could cause a disability of mir-1269 on binding with sox6 which interfered the specific function of mir-1269 . 23177026_1 fasl is a direct target of mir-21 in pancreatic cancer. 23177026_2 these results were observed in both hek293 cells and the pancreatic cancer panc-1 cell line , which indicates that mir-21 suppresses fasl expression through the mirna-binding sequences within the fasl 3' utr. 23177026_3 therefore, the results from our study indicate that fasl is a direct target of mir-21 in pancreatic cancer. 23177026_4 taken together, these results suggest that mir-21 expression suppresses fasl expression and protects pancreatic cancer cells from gemcitabine-induced apoptosis . 19854497_1 mir-200 family members are expressed at low or negligible levels in normal ovarian surface cells and substantially increase in expression in ovarian cancer, whereas expression of zeb1 and zeb2 shows the opposite pattern. 19854497_2 there is reciprocal repression between mir-200 family members and zeb transcription factors, creating a double negative regulatory feedback loop resembling that reported in other cancer cell types. 19854497_4 conclusion: analysis of ovarian cancer tissues suggests that ovarian surface cells acquire a more epithelial mir-200-zeb1/2 phenotype as they undergo transformation, switching from a mir-200 familylow and zeb1/2high state to a mir-200 familyhigh and zeb1/2low phenotype. 21740905_1 in this study, we identified four differentially expressed mirnas between two premeiotic male germ cells, made predictions about their putative targets, and confirmed cyclin t2 as a direct target of mir-15a. 21740905_3 fig. 2. mir-15a directly targets the 3'-utr of ccnt2. 21740905_4 briefly, mir-15a negatively affected muscle differentiation by partly targeting ccnt2 at least. 16885212_1 nf-kb can induce the expression of mir-146a, which can then down-regulate irak1 and traf6 and thus acts as a component in a negative feedback loop that controls tlr signaling. 26885274_1 indicated ywhaz was a target gene of mir-451 in 293t cell lines . 26885274_2 mir-451 negatively regulates ywhaz expression via targeting ywhaz 3'-utr. 19265035_2 this reduction is required for the rapid upregulation of its target, hypoxia-inducible factor -1alpha. replenishing mir-199a during hypoxia inhibits hif-1alpha expression and its stabilization of p53 and, thus, reduces apoptosis. 19265035_3 on the other hand, knockdown of mir-199a during normoxia results in the upregulation of hif-1alpha and sirtuin 1 and reproduces hypoxia preconditioning. 19265035_4 sirt1 is also a direct target of mir-199a and is responsible for downregulating prolyl hydroxylase 2, required for stabilization of hif-1alpha. 26622447_1 a luciferase reporter assay was then conducted, which identified cdc42 as a direct target of mir-195, and the expression of cdc42 was significantly upregulated in bladder cancer tissues, as determined by western blotting. 26622447_2 furthermore, mir-195 negatively regulated the protein expression of cdc42 in bladder cancer cells. 26622447_3 identification of cdc42 as a novel target of mir-195. 26622447_5 3, the protein level of cdc42 was notably decreased in t24 cells transfected with mir-195 mimic, while increased in t24 cells transfected with mir-195 inhibitor, indicating that mir-195 negatively regulates the protein level of cdc42 in bladder cancer t24 cells. 22005523_1 downregulation of mir-130b promotes the development of multidrug resistant ovarian cancer partially by targeting the 3'-utr of csf-1, and the silencing of mir-130b may be mediated by dna methylation. 22005523_2 the mimics transfection dramatically inhibited csf-1 expression on both mrna and protein level in a2780/cp, a2780/tax and skov3/tax cells , and the mir-130b inhibitors transfection resulted in significant increases in csf-1 protein expression of a2780 and skov3 cells . 22005523_3 the luciferase expression increased to 1.57-fold by mut 1, 1.76-fold by mut 2, and 2.00-fold by mut 12 compared to wildtype , suggesting mir-130b negatively regulates csf-1 expression by direct binding to 3'-utr of csf- 1 mrna. 22005523_5 5a and s3, mir-130b inhibitors significantly increased ic50 for cisplatin and paclitaxel in a2780 and skov3 cells, and this resistance-inducing effect was greatly attenuated by csf-1 knockdown, suggesting down-regulation of mir-130b induces impaired sensibility of ovarian cancer cells to chemotherapeutic agents at least in part by targeting csf-1. 23323620_1 in 293 cells, luciferase reporter assay results demonstrated that aldh2 was a direct target of mir-34a. 23894561_1 bioinformatics analysis and functional studies indicated that mir-29b and mir-29c were 2 key mirnas involved in tlr-inhibited gc-induced pdc apoptosis. 26463633_1 mir-30a directly targets and inhibits beclin-1 expression. 26463633_2 we found that mir-30a has the seed region that matched the 3'-utr of beclin-1. 20719859_1 using a luciferase reporter assay, we confirmed that mir-448 targets the klf5 3'utr. 20719859_2 to further confirm this specificity, we mutated the candidate mir-448 target sites , which resulted in the loss of mir-448-mediated repression . 20719859_3 to further confirm that klf5 is the target of mir-448, we examined the effect of decoy mir-448 with or without the depletion of klf5. 20616003_1 mir-125a inhibits immature hematopoietic cell apoptosis and target bak1. 20616003_2 consistent with the observation that mir-125a is the single microrna within the mir-99b-let-7e-mir-125a cluster that mediates hsc expansion, mir-125a inhibited the bak1 3'-utr construct , whereas mir-99b and let-7e had minimal effect. 26278151_1 luciferase reporter assays and western blots showed that dlc1 was a direct target of mir-141 in crc. in conclusion, we demonstrated that mir-141 is up-regulated in crc and acts as a functional oncogene by targeting dlc1. 26278151_2 the relative luciferase activity of hek293t cells transfected with mir-141 in the presence of the wild-type dlc1 3'-utr was significantly suppressed, whereas that containing the mutant dlc1 3'-utr was unaffected , indicating that mir-141 may suppress dlc1 gene expression through the 3'-utr binding and silencing of dlc1 mrna. 26477310_1 the mirna mir-22 represses de novo fatty acid synthesis and elongation by targeting acly and long-chain fatty acid elovl6 22378464_1 genome-wide molecular target search and luciferase reporter assays showed that prothymosin-alpha and purine nucleoside phosphorylase are directly regulated by mir-1 and mir-133a. 26260454_2 consistent with our hypothesis, we discovered that over-expression of mir-200c reduced the dlc-1 expression whereas the inhibition of mir-200c resulted in up-regulation of dlc-1 expression . 26260454_3 our in vitro data showed that the down-regulation of mir-200c causes up-regulation of the tumor suppressor gene, dlc-1. 19620785_1 we examined the role of the muscle-specific mirnas mir-1 and mir-206 in human rhabdomyosarcoma , a soft tissue sarcoma thought to arise from skeletal muscle progenitors. 19620785_2 we have shown that mir-1 was barely detectable in primary rms of both the embryonal and alveolar subtypes and that both mir-1 and mir-206 failed to be induced in rms cell lines upon serum deprivation. 19620785_3 moreover, reexpression of mir-206 in rms cells promoted myogenic differentiation and blocked tumor growth in xenografted mice by switching the global mrna expression profile to one that resembled mature muscle. 19620785_4 finally, we showed that the product of the met proto-oncogene, the met tyrosine-kinase receptor, which is overexpressed in rms and has been implicated in rms pathogenesis, was downregulated in murine satellite cells by mir-206 at the onset of normal myogenesis. 19620785_6 we propose that tissue-specific mirnas such as mir-1 and mir-206, given their ability to modulate hundreds of transcripts and to act as nontoxic differentiating agents, may override the genomic heterogeneity of solid tumors and ultimately hold greater therapeutic potential than single gene-directed drugs. 25169552_2 studies indicated that mir-15a may directly interact with the 3'-untranslated region of sncg mrna, downregulating its mrna and protein expression levels. 20956382_1 these results suggest the direct binding of mir-1/mir-206 to the m1 and/or m2 sites within the longer 3'utr of pax3. 20956382_2 semiquantitative rt-pcr data clearly showed that the longer 3'-utr was used for pax3 expression in myod / myoblasts , suggesting that mir-1/mir-206 may negatively regulate pax3 expression through binding to m1 and/or m2 sites. 20956382_3 these results strongly suggest that myod regulates the transcription of mir-1/mir-206 expression, which in turn directly suppresses pax3 expression in myoblasts. 20956382_4 pax3-3'-utr is a targetfor mir-1 and mir-206. 25179844_2 the luciferase assay confirmed that mir-449a functioned through suppressing notch1 directly. 22956783_2 mir-181a targeted the 3' untranslated region of c-fos mrna by luciferase experiments. 22956783_3 microrna-181a represses ox-ldl-stimulated inflammatory response in dendritic cell by targeting c-fos. 25098679_1 furthermore, we proved that mir-31 suppressed the npc cell growth via targeting fih1 and mcm2. 20558719_2 the difference in mir-27 abundance correlates with up-regulation of the foxo1 protein in the presence of hsurs 1 and 2, which suggests that these hvs ncrnas perturb host gene expression via the mirna pathway. 20558719_3 knockdown of hsur 1 but not of hsur 2 correlated with higher levels of mir-27 and with lower levels of the mir-27 target protein, foxo1 , which suggests that hsur 1 is specifically involved in regulating mir-27. 26458859_1 furthermore, mir- 26a has target sites in the 3'utr of nras and e2f2 by luciferase reporter assay and reduces the expression levels of nras and e2f2. 26458859_2 our results suggest that mir- 26a can improve the sensitivity of gc cells to cisplatin-based chemotherapies through targeting nras and e2f2, and provide the first evidence of the potential utility of mir- 26a as a sensitizer in chemotherapy for gc. 26458859_3 these data support that mir- 26a directly targets 3'utrs of nras and e2f2. in contrast, knockdown of mir- 26a increased their expression levels in sgc- 7901 cells , further indicating that nras and e2f2 are the targets of mir- 26a in osteosarcoma cells. 26400206_1 mir-200c suppressed notch1 and panc -1 self-renewal ability. 23457043_2 luciferase reporter assay analysis confirmed the direct binding of mir-146a and prkce 3'-utr. 23457043_3 specific overexpression of exogenous mir-146a significantly decreased pkcepsilon levels in ptc cell line npa-187 and increased apoptosis. 25504437_1 this result was confirmed by western analysis showing that mir-125a-5p overexpression decreased hdac4 protein levels in vitro, but not hdac1 or hdac2, which do not contain the targeting sequence of mir-125a-5p in their mrna sequences . 25504437_2 these data indicate that mir-125a-5p directly targets hdac4 in human breast cancer. 25504437_3 overall, these results suggest that mir-125a-5p blocks tumor development by targeting hdac4. 26079153_1 taken together, these results indicate that mir-200b/200c/429 negatively regulates crkl by directly targeting its 30 -utr region. 26079153_2 these results suggest that mir-200c regulates cancer cell invasion partially through targeting crkl. 25505246_1 microrna-146a and microrna-146b regulate human dendritic cell apoptosis and cytokine production by targeting traf6 and irak1 proteins. 25505246_2 mir-146a and mir-146b expression in imdcs and mdcs was inversely correlated with traf6 and irak1 expression. 26152285_1 overexpressing tnfaip1 had similar effect as down-regulating mir-181a in pancreatic cancer. 26152285_2 thus, both mrna and protein levels of tnfaip1 were negatively regulated by mir-181a in pancreatic cancer cells. 26152285_3 therefore, our results suggest that tnfaip1 overexpression has similar tumor-suppressive effects as mir-181a down-regulation in pancreatic cancer. 26152285_4 therefore, our xenograft assay suggests that mir-181a has anti-tumor effect on pancreatic cancer and negatively modulates tnfaip1 in vivo. 25322940_2 the overexpression of mir-143 was able to downregulate the expression of atg2b at the transcriptional and translational levels by direct binding to its 3' untranslated region. 26526683_1 consistent with the blocked mir825 and mir825* function, the target genes were upregulated in the sttm825/825* transgenic plants . 26526683_3 these results, together with the results from transgenic plants, indicated that these genes were the direct targets of mir825 and mir825*, and were involved in the modulation of ar156-primed isr against pst dc3000. 26339601_1 qpcr and in silico hybridization revealed that mir-124 and mir-155 can be directly involved in the transcriptional regulation of runt-related transcription factor 2 and receptor activator of nuclear factor kappa-b ligand genes. in silico hybridization revealed that seed regions mir-124 and mir-155 can bind with the untranslated regions of the runx2 and rankl . 26339601_3 validation of mirnas using qpcr demonstrated that sublethal concentrations of naf can significantly upregulate mir-124 and mir-155 expressions in hos cells . 22917031_1 our data suggest that let-7c contributes to endothelial apoptosis through suppression of bcl-xl. 21764575_1 in accordance with a diminished mir-302a expression on the wtd, hepatocyte mrna expression levels of mir-302a targetgenes abca1 and in particular elovl6 were increased in response to wtd . in contrast, in accordance with a diminished mir-302a expression/function, the relative expression levels of the mir-302a target abca1 and in particular elovl6 were increased in response to the wtd in hepatocytes of ldlr / mice. 26388700_1 bioinformatics analysis identified cthrc1 as a target of mir-30b and western blotting and luciferase reporter assays confirmed that mir-30b regulates cthrc1 by directly binding to its 3'utr. 26388700_2 transfection of cthrc1 without the 3'utr restored the mir-30b inhibiting cell invasion. 26388700_3 up-regulation of mir-30b or down-regulation of cthrc1 had potential significance in the invasion and metastasis of nsclc. 26388700_4 these findings strongly suggest that mir-30b down-regulates the expression of cthrc1 by binding to its 3'-utr. 26388700_5 these results further suggest that cthrc1 is a major target of mir-30b, and expression of cthrc1 restores mir-30b anti-invasion function. 26309510_1 luciferase assays using a reporter carrying a putative mir-145 target site in the 3- untranslated region of dusp6 revealed that mir-145 directly targets dusp6. 26309510_2 the overexpression of mir-145 inhibited tpc1 cellular growth by targeting dusp6; this finding implies a better understanding of initiation and progression of papillary thyroid cancer. 26309510_3 in this study, we found overexpression of mir-145 inhibited cells- growth, most likely targeting dusp6. in addition, mir-145 mimics control cells, demonstrating that mir-145 specifically binds to the 3'-utr of dusp6 mrna. 26309510_4 our study revealed that mir-145 inhibited cellular growth in papillary thyroid cancer by targeting dusp6, which may act through a newly determined and a classical signal pathway-the mapk pathway and may provide additional evidences to further prove mir-145 is a potent tumor suppressor gene in papillary thyroid cancer. 26470727_1 in accordance with the negatively correlated expression pattern of mir-9 and foxo1 and overrepresented mir-9 signature in the foxo-null nspc transcriptome, we hypothesized that foxo1 could be regulated by mir-9 26420356_1 as a potential target gene of mir-107, glt-1 mrna and protein expression was significantly down-regulated in brain tissue following i/r accompanied by elevated plasma levels of glutamate, and these changes were reversed by mlb treatment except the effect on glt-1 mrna expression . 22446332_2 mir-181b could be induced by tgf-b1 and promote the growth of hscs by directly targeting p27. 21934093_2 in other words, the cases with the rs8126 cc genotype, which has the perfect complementary seed sequence for mir-184, had lower levels of tnfaip2 expression than did cases with the tt genotype. 21934093_3 taken together, these findings indicate that the mir-184 binding site snp in the 3' utr of tnfaip2 is functional by modulating tnfaip2 expression and contributes to scchn susceptibility. 21934093_5 relative expression levels of tnfaip2 mrna and mir-184 in pbmcs of 64 scchn cases with known tnfaip2 genotypes. 21934093_6 our results indicate that the tnfaip2 c allele, located in the mir-184 binding site, is likely to disrupt mirna target interaction, resulting in the alteration of tnfaip2 mrna expression, a possible underlying mechanism for the observed association with increased risk of scchn. 21934093_7 however, the exact effect of rs8126 on the binding between mir-184 and tnfaip2 still need further investigation by functional studies. 25712341_1 to precisely determine the expression levels of mir-146a/b and their target genes irak1 and traf6, we isolated the prostate cancer cells from tumor tissues by lcm. to determine whether downregulation of nuclear foxp3 contributes to mir-146-nf-κb signaling in prostate cancer, we analyzed the expression of mir-146a/b, irak1, and traf6 in microdissected cancer cells. in contrast to mir-146a/b expression levels, mrna expression of irak1 and traf6 was significantly lower in nuclear foxp3+ cancer cells than in foxp3- cancer cells . 26337230_1 the results of qrt-pcr analysis showed that mir-365 expression level was significantly lower in nsclc serum samples than in healthy control serum samples , while ttf-1 mrna expression level was significantly increased in nsclc serum samples compared to healthy control serum samples. 26337230_2 the relative expression levels of mir-365 in sera of nsclc patients were negatively correlated with those of ttf-1 mrna significantly. 26337230_3 we found that low mir-365 expression and high ttf-1 expression, alone or in combination, were all significantly associated with poor differentiation , advanced tnm stage and positive lymph node metastasis of nsclc patients. 22787204_1 introduction of anti-mir-130a in hepatocytes increased ifitm1 expression. 22787204_3 together, these results suggested that hcv infection of hepatocytes upregulates mir-130a and that use of anti-mir-130a may have potential for restriction of hcv replication. 26064277_1 potential target of mir-615 was predicted using targetscan 6.2, we found that akt2 was a potential target of mir-615. 26064277_2 western blotting analysis showed that mir-615 mimics markedly suppressed akt2 protein levels in mda-mb-231 cells , while mir-615-in clearly promoted akt2 protein expression. 26064277_3 the luciferase assay showed that mir-615 significantly led to the suppression of luciferase activity , indicating that mir-615 directly bound to its predicted binding site on akt2. 26064277_4 meanwhile, mir-615-mut had no effect on the luciferase activity of akt2 3'-utr wild type. 26064277_5 these results, taken together, demonstrated that akt2 is a bona fide target of mir-615. 26861148_1 mir-502-5p targeted the 3 ' -untranslated region of traf2 to inhibit its expression. 26861148_2 the results suggested that mir-502-5p was able to bind directly to the 3 ' -utr of traf2 mrna to suppress the translation. 21310958_2 we also identified sprouty homolog 1 as a direct target of mir-29c with a nearly perfect complementarity between mir-29c and the 3'-untranslated region of mouse spry1. 25198665_1 further, we observed an obvious inverse correlation between fscn1 and mir-133a levels in tumor samples, and fscn1 was confirmed as a direct target of mir-133a by using luciferase reporter assay. 25198665_2 these data indicate that fscn1 is a direct target of mir-133a in pancreatic cancer. 23913306_1 our in vitro study demonstrated that mir-224 played an oncogenic role in hepatoma cell migration and tumor formation through silencing its target gene smad4. 26686085_1 in contrast, the mutant luciferase activity was nearly comparable between nf魏b2+/+ and nf魏b2+/鈭抍ells , suggesting that mir-494 has an essential role in nf魏b2-mediated regulation of pten via directly targeting pten-3'-utr. 26686085_2 to further verify the role of mir-494 in regulation of pten expression, mir-494 expression construct was stably transfected into both nf魏b2+/+ and hct116 cells. 26686085_3 overexpression of mir-494 significantly inhibited pten expression and increased akt phos-phorylation . 20550618_1 microrna-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting rip1. 21606534_1 hepatitis c virus infection and hepatic stellate cell activation downregulate mir-29: mir-29 overexpression reduces hepatitis c viral abundance in culture. 23990798_1 the intronic long noncoding rna anrassf1 recruits prc2 to the rassf1a promoter, reducing the expression of rassf1a and increasing cell proliferation. 24300912_2 using mir-33 srebf1 mice, we demonstrate that srebp-1 is a target of mir-33 and that the mechanisms leading to obesity and liver steatosis in mir-33 mice involve enhanced expression of srebp-1. 24300912_3 figure 5 srebf1 is a mir-33 target gene. 22458297_1 in other words, disruption of this stabilizing element may account for yaho degradation upon micf induction. 20435064_1 luciferase assay co-transfecting with the two constructs showed that the mirnas, mir-19b, mir-302b* and mir-323-3p could repress gene expression in hek-293 cells,suggesting a role of these mirnas in the regulation of the fmr1 expression. 20435064_2 the result showed that, co-transfecting with the pre-mirnas expression constructs, the mt1 , mt2 and mt4 mutation constructs resulted in a significantly increase in luciferase activity comparing to that of the wild-type construct , suggesting that the mirnas, mir- 19b, mir-302b* and mir-323-3p, could repress gene expression in hek-293 cells. 26708715_2 these results indicate that mir-217 directly bindings to the 3'-utr of igf-1r and inhibits its expression. 26708715_3 these results indicated that mir-217 inhibits eoc growth and metastasis partially by targeting igf1r. 23045399_1 these data suggest that a trophic hormone and camp inversely regulate the expression of sr-bi and mirna-125a and mirna-455 in steroidogenic tissues/cells and that both mirna-125a and mirna-455, by targeting steroidogenic sr-bi, negatively regulate selective hdl ce uptake and hdl ce-supported steroid hormone. 23143396_1 levels of mir-16 and let-7a, measured by northern blot or rt-qpcr, indeed decreased significantly in cells treated with sirnas targeting ndp52, atg5 or atg7, but not p62, for an extended period of 4 days . in contrast, pre-mir-16 and pre-let-7a levels were not overtly modified suggesting that prolonged defects in autophagy specifically affect mirna stability after pre-mirna processing, but before mirisc formation and activity. 26227218_1 histological staining also showed that pokemon abundance was relatively lower in mir-125-high hcc samples than low mir-125 group . in hcc cells, the inverse association between mir-125 and pokemon was consistently confirmed. 26227218_2 we found that there are three potential recognition sites of mir-125 within the 3'-utr of pokemon. 26227218_4 we showed that mir-125 suppresses the expression of pokemon in hcc cells. 25246803_2 especially, it has been demonstrated that mir-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting pten. 19647520_1 here we show that degradation of mrna of -betatrcp1 is mirna-dependent, and identified mir-183 as a microrna that interacts with the coding region of -betatrcp1 mrna. 19647520_2 indeed, elevated levels of -betatrcp1, achieved by inhibition of mir-183 function, accelerated the degradation of known -betatrcp1 substrates such as -beta-catenin and ikappabalpha , inhibition of -beta-catenin-driven transcriptional activity and decreased expression of -beta-catenin/tcf targetgenes . 18057241_1 through mirna microarray analysis, we demonstrate that lmp1 dysregulates the expression of several cellular mirnas, including the most highly regulated of these, mir-146a. 18057241_2 quantitative reverse transcription-pcr analysis confirmed induced expression of mir-146a by lmp1. 18057241_3 reporter studies demonstrated that lmp1 induces mir-146a predominantly through two nf-kappab binding sites in the mir-146a promoter and identified a role for an oct-1 site in conferring basal and induced expression. 26473412_1 we also identified arfgef1 and paxillin as novel targets of mir-27b, and found that mir-27b-mediated regulation of arfgef1 is crucial for controlling anchorage-independent growth, and that of paxillin is important for controlling cell adhesion and invasion. 26473412_2 we also show that mir-27b directly targets arfgef1 and paxillin to suppress tumor growth and invasion in human colon cancers, and that mir-27b-mediated repression of paxillin attenuates focal adhesion-mediated signaling. 26473412_3 microrna-27b directly targets arfgef1 and paxillin, which are required for tumor growth and cancer cell adhesion/invasion, respectively. 24913918_1 altogether, we conclude that mir-581 promotes hbsag expression by targeting dicer and edem1. 24913918_2 our findings suggest that downregulation of mir-581 during hepatocarcinogenesis may lead to a reduction in hbsag expression and impede hcc development. 22771905_1 in the present study, we found that mir-155, an ifn--beta-induced mirna, mediated the suppressive effect of ifn--beta on osteoclast differentiation by targeting socs1 and mitf, two essential regulators of osteoclastogenesis. 22771905_2 our data suggest that mir-155 is induced by ifn--beta, and mediates the suppressive effect of ifn--beta on osteoclast differentiation by targeting socs1 and microphthalmia-associated transcription factor , two positive regulators during osteoclastogenesis. 22771905_3 our data indicated that mir-155 could target socs1 and mitf during osteoclastogenesis, therefore, mir-155 might inhibit osteoclast differentiation by targeting socs1 and mitf, thus at least partially mediate the suppressive effect of ifn--beta on osteoclastogenesis. 20945401_1 furin was confirmed as a novel target of mir-24 by 3' utr luciferase assay and western blot. 20945401_2 specifically, mir-24 might play an important role in modulating the induction of tgf-beta1 mediated by cms through direct targeting of furin. 20945401_3 furin was among the genes significantly down-regulated by mir-24 and computational predictions indicated that mir-24 shares complementarity with the 3'-utr of furin. 20945401_5 furin down-regulation was confirmed at protein level after transfection with mir-24 or scrambled . 22479552_1 our results suggest that mir-141 suppressed hbv replication by reducing hbv promoter activities by down-regulating ppara. 20201611_2 data showed that gvt treatment of ts1-infected mice significantly increased their expression of bcl-2 and vegf in brainstem compared with ts1-infected untreated mice. 20201611_3 we also studied the expression of specific micrornas such as mirna-15 and -16 , and mirna-20 . 25587085_1 mir-34a specifically repressed lef1 expression through direct binding to its 3'-untranslated regions . 25587085_2 mir-34a modulated the levels of lef1 to regulate emt in prostate cancer cells. 25587085_3 functionally, mir-34a negatively correlated with the migration and invasion of prostate cancer cells through lef1. 25652288_1 moreover, we identified that mir-126 directly targeted pik3r2 and affected pi3k/akt signaling axis. in this study, we discovered that mir-126 enhanced epcs migration and tubulogenic activity, by targeting pik3r2 directly. 25652288_2 taken together, these data implied that mir-126 may attenuate the expression of pik3r2 by directly targeting the 3'-utr of pik3r2. 25652288_3 these results showed that mir-126 directly targeted pik3r2 and involved in the regulation of pi3k/akt signaling pathways. 21471522_1 to ascertain that mcl-1 can be targeted by mir-29a in alk+ cells, we performed a gain-of-function experiment of mir-29a in karpas-299, su-dhl-1, and cost cells. 21471522_2 mir-29a or a mir negative control was transiently transfected and endogenous mcl-1 expression was detected by western blotting . 21471522_3 figure 5 mir-29a targets mcl-1 in npm-alk+ alcl cells. 21471522_4 mir-29a-搕ransfected tumors displayed a significant increase of apoptotic cells with respect to the control , that correlated with mcl-1 protein down-expression . 21471522_5 these results support a tumor suppression effect of mir-29a in vivo, via a decreased mcl-1 expression. 25003638_2 integrated analysis identified lim domain kinase 1 as a direct and functional target of mir-143. 25003638_3 overexpression of limk1 attenuated the tumor suppressive effects of mir-143 in nsclc cells. 25003638_4 moreover, mir-143 was inversely correlated with limk1 expression in nsclc tissues. 25003638_5 together, our results highlight the significance of mir-143 and limk1 in the development and progression of nsclc. 22510686_1 mir-484 is able to attenuate fis1 upregulation and mitochondrial fission, by binding to the amino acid coding sequence of fis1 and inhibiting its translation. 22510686_2 in exploring the underlying mechanism of mir-484 downregulation upon apoptosis, we observe that foxo3a transactivates mir-484 expression. 22510686_3 our present study shows that mir-484 can repress fis1 expression and is able to inhibit mitochondrial fission through targeting fis1. 22510686_4 mir-484 targets the amino acid coding sequence of fis1. 26101704_2 we also generated mutated luciferase constructs , and introduced these constructs into the mir-135b binding site of lats2 3'-utr. 26101704_3 we found that the binding site was responsible for the role of mir-135b in regulating lats2 expression. 26101704_4 our data indicate that mir-135b is able to target lats2 directly, and that lats2 may contribute to chemoresistance. 19903841_1 these data suggested that a clear inverse correlation existed between mir-15a and mir-16 levels and bmi-1 expression. 19903841_2 mutation of the single mir-16 site rescued the luciferase activity, thus confirming a direct interaction of mir-16 with the 3'-utr of bmi-1 mrna. 19903841_3 thus, after determining that mir-15a and mir-16 target the 3'-utr of bmi-1 as well as downregulate bmi-1 protein levels, we next wanted to determine the effect of these mirnas on the proliferation and clonal growth of ovarian cancer cells. 19903841_4 these results prove that in ovarian cancer, mir-15a and mir-16 indeed regulate proliferation and clonal growth through downregulation of bmi-1. 21221132_1 ectopic expression of mir-k12-11 resulted in decreased ikk expression, while inhibition of mir-k12-11 was found to restore ikk expression in kshv-infected cells. 23437304_1 ectopic expression of mir-18a significantly inhibited the repair of dna damage induced by etoposide , leading to accumulation of dna damage, increase in cell apoptosis and poor clonogenic survival.mir-18a 26317551_1 dual-luciferase report assays demonstrated that mir-106b directly targets c1orf24 by binding its 3'-utr. 26317551_2 we provide evidence that c1orf24 expression is directly regulated by mir-106b. 26317551_3 these results support the hypothesis that mir-106b directly interacts to and negatively regulates c1orf24 expression by binding to its 3'-utr mrna. 26762119_1 dual-luciferase reporter assay showed that cdkn1a is a target of mir-20a. 26762119_2 luciferase activity was significantly repressed when mir-20a was co-expressed with the 3'-utr of cdkn1a , whereas luciferase activity in mutated 3'-utr of cdkn1a did not change , indicating that mir-20a suppressed the expression of p21 by directly binding to 3'-utr of p21 mrna. 26762119_3 our results indicate that the effect of stroke serum priming on the increased proliferation rate of mscs is related to the up-regulation of mir-20a, which regulates the cell cycle inhibitor p21 cdkn1a. 26400524_1 based on the dual luciferase assay and western blot analysis, we confirmed that both mir-21 and mir-183 can simultaneously target socs6 and modulate its expression at protein level. 26400524_2 both mir-21 and mir-183 can directly target socs6 and modulate its expression. 21145002_1 by screening gal4 enhancer traps with a uas-gfp-mcd8 reporter, we found that insertions upstream of the mir-310, -311, -312, -313 cluster exhibited activity in larval stage motor neurons. 21145002_2 these results are consistent with khc-73 being a key target of the mir-310 cluster. 21145002_3 while reducing khc-73 in motor neurons using a knockdown transgene did not significantly affect synaptic transmission, overexpression of khc-73 induced a strong increase in qc , phenocopying the effect of deleting the mir-310 cluster, thus further supporting the link between khc-73 and the mir-310 cluster. 21145002_4 our findings show that khc-73 transgene with 3- utr is much more sensitive to the endogenous levels of mir-310. 21145002_5 these results together provide strong evidence indicating that khc-73 is the relevant target of mir-310 cluster in vivo and provide some of the first evidence for in vivo relationship between mirnas and their target through seed sequences within the coding region. 21145002_6 these results together suggest that the regulation of khc-73 by mir-310 cluster in motor neurons is essential for the ability of retrograde signalling at the nmj to regulate presynaptic neurotransmitter release. 26052614_1 regulation of lamc1 and mcl1 expression by mir-22 and mir-29a, respectively, was further investigated by reporter gene assays. 26052614_3 thirty-six hours after cotransfection of pc3 cells with reporter gene and either antimirs or mirna mimics, a significant up- or down-regulation of the reporter gene activity was measured confirming the predicted modulation by mir-22 and mir-29a . 26052614_4 as hypothesized, higher mir-22 and mir-29a levels in the benign tissue were associated with a decreased amount of their target proteins, lamc1 and mcl-1. 26589234_1 we selected hsa-mir-193a-5p as it was shown to be down regulated in our array data and also predicted to target il-12b. 26589234_2 upon transfection of thp-1 cells with pre-mir-193a-5p, the transcript level of il-12b was clearly less in mimic-transfected group . 25197360_1 one encompassing the proximal half of the 3'-utr also including the predicted mir-27a binding site, and a second overlapping construct containing the distal half without the mir-27a binding site . 25197360_4 downregulation of cellular mir-27a in achn cells increased the expression of the mcph1 protein. 22487517_1 mir-15b and mir-16 could induce apoptosis of rat pscs by targeting bcl-2. 23933812_1 using the lncrna rt-pcr array carrying 83 human disease-related lncrnas, we show that mir-21 is capable of suppressing the lncrna growth arrest-specific 5 . 23933812_2 this negative correlation between mir-21 and gas5 is also seen in breast tumor specimens. of interest, gas5 can also repress mir-21 expression. 23933812_3 whereas ectopic expression of gas5 suppresses, gas5-sirna increases mir-21 expression. 23933812_4 importantly, there is a putative mir-21-binding site in exon 4 of gas5; deletion of the mir-21-binding site abolishes this activity. 23933812_6 we further show that the biotin-labeled gas5-rna probe is able to pull down the key component of the rna-induced silencing complex and we subsequently identify mir-21 in this gas5-risc complex, implying that mir-21 and gas5 may regulate each other in a way similar to the microrna-mediated silencing of target mrnas. 21993663_1 we demonstrated that mir-200bc/429 cluster might play an important role in the development of mdr in human gastric and lung cancer cell lines by targeting the anti-apoptotic genes bcl2 and xiap. in both sgc7901/vcr and a549/cddp cells, a significant decrease in relative luciferase activity was noted when pgl3-bcl2-3'-utr or pgl3-xiap-3'-utr was co-transfected with the mir-200bc/429 cluster mimics, but not with the mirna mimic control, respectively , suggesting that bcl2 and xiap were the common targetgenes of the mir-200bc/ 429 cluster. 21993663_2 since bcl2 and xiap were both anti-apoptotic protein and the target of the mir-200bc/429 cluster, we hypothesized that the mir-200bc/429 cluster might modulate multidrug resistance of cancer cells via inhibiting the bcl2 and xiap protein expression. 21993663_3 these results suggested that mir-200bc/429 might modulate multidrug resistance of cancer cells at least in part by inhibiting the bcl2 and xiap protein expression. 21820586_2 these findings indicate that mir-21 modulates fasl and timp3 expression by binding the 3' utr of these genes. 21820586_4 however, when we transfected with timp3 lacking 3' utr and mir-21, expression of timp3 largely overrode the mir-21 anti-apoptosis function. 21820586_5 these results indicate that timp3 is a major target of mir-21. 21820586_6 figure 2. fasl and timp3 identified as targetgenes of mir-21. 26101708_1 mir-30c directly targeted the ier2 3'-utr. 26852921_1 interestingly, though both smad6 and smad7 are the targets of mir21, there is lack of reports that mir-21 could regulate smad6 in colon cancer cells, to the best of our knowledge. 26852921_2 to examine the smad6 expression level treated with and without inhibition of mir-21, pcr analysis were implemented. 26852921_3 as our expected, results show that the expression level of smad6 is becoming significantly higher when inhibit the level of mir-21 in colon cancer cells . 21878637_2 these data suggest that mir-99a may suppress gene expression by directly binding to the 3'-utr of igf-1r and mtor. 21878637_3 figure 7.mir-99a directly target igf-1r and mtor. 21878637_4 markedly, igf-1r and mtor protein levels were both inversely correlated with the mir-99a expression level in hcc tissues . 21878637_5 collectively, these results imply that endogenous levels of igf-1r and mtor in liver tissues can be negatively regulated by mir-99a. 26296572_1 in silico analysis indicated that hsa-mir-23a-3p and hsa-mir-29a-3p target the coding region of cyp2c19 with hybrid stabilities of - 27.5 kcal/mol and - 23.3 kcal/mol, respectively. 26296572_2 rna electrophoresis mobility shift assays showed that both hsa-mir-23a-3p and hsa-mir-29a-3p mirnas were able to bind directly to their cognate targets in the cyp2c19 transcript. 26296572_3 however, our strategy did predict that hsa-mir-23a-3p and hsa-mir-29a-3p might efficiently interact with the coding region of cyp2c19. 21368878_1 antiapoptotic genes bcl2l2 and e2f6 are identified as the targets of mir-205 and mir-31, respectively. 21368878_2 the bcl2l2 mrna contains a 3' untranslated region sequence that is partially complementary to mir-205, and the e2f6 mrna has a 3' utr recognized by mir-31 . 26549849_1 we identified the methyltransferase ash1l as a pivotal target of mir-291 mediating this effect. 26549849_2 however, we discovered that mir-291 regulated another trithorax group protein, the h3k36 methyltransferase ash1l. 26549849_3 ash1l is a predicted target of mir-291, which we validated using reporter assays. 26096783_1 loxl2 was a direct target gene of mir-29s, as shown by genome-wide gene expression analysis and luciferase reporter assay. 26096783_3 these data suggested that mir-29s bound directly to two specific binding sites in the 3 ' -utr of loxl2 mrna. in this way, we identified loxl2 as a target gene of tumour-suppressive mir-29s and validated the direct binding of this mirna to the 3 0 -utr of loxl2 using luciferase reporter assays. 24505359_1 we also found that mir-545 caused cell cycle arrest at the g0/g1 phase and induced cell apoptosis in lung cancer cells by targeting cyclin d1 and cdk4 genes. 24505359_2 the effects of cyclin d1 and cdk4 down-regulated by mir-545 were similar to those caused by sirnas of cyclin d1 and cdk4, and overexpression of cyclin d1 and cdk4 could abolish the mir-545-induced inhibition of cell proliferation. 22073238_1 igf-1r was the functional targetfor mir-223 suppression of cell proliferation and its downstream pi3k/akt/mtor/p70s6k pathway suppressed by mir-223 was by targeting igf-1r. 22073238_2 transfection with igf-1r cdna could totally overcome the suppression caused by mir-223 since the construct contained no 3'-utr. 22073238_3 in the tumor tissues at xenograft nude mice, the expression of igf-1r was also suppressed in mir-223 group as compared with ev group . 22073238_4 figure 3 igf-1r was directly targeted by mir-223. 22073238_5 these results strongly indicated that mir-223 suppressed of akt/mtor/p70s6k pathway is by targeting igf-1r. 22073238_6 this result suggested that mir-223 targeted igf-1r not only in hela cells, but also in leukemia and hepatoma cells. 19102781_1 here we report the functionality of predicted mir-29a target site in the hiv-1 nef gene.our 19102781_2 results show that the cellular mirna hsa-mir29a downregulates the expression of nef protein and interferes with hiv-1 replication. 23517578_1 transfection of cd8+ t cells with mirna-15b mimics could prevent t cells from apoptosis by inhibiting the translation of dedd . 26544536_2 and hsa-mir- 145 rna levels in umuc2 cells transfected with hsa-miir- 145 mimic and negative control or hsa-mir- 145 inhibitor and negative control. 26469406_1 additionally, mir-26a directly targeted the 3'utr of the gsk3-beta, suppressing the expression of gsk3-beta protein. 26469406_2 taken together, our data showed that mir-26a suppressed the protein levels of gsk3-beta, whereas the knockdown of mir-26a increased gsk3-beta protein expression. 26469406_3 furthermore, mir-26a repressed the translation of gsk3-beta by directly binding to position 4636- 4643 of the gsk3-beta 3'-utr. 26469406_4 these findings suggested that gsk3-beta was a direct target of mir-26a. 25460509_2 collectively, fbxo45 is a direct target of mir-27a* in cells. 25460509_3 taken together, these data demonstrated that mir-27a* mediates tumor cell emt processes through stabilizing the core emt-tfs by direct suppression of fbxo45 that is a module of spf ubiquitin e3 complex. 23169590_3 inhibition of mir-451 expression correlated with increased ywhaz protein expression and decreased zfp36 expression, providing a possible mechanism for the elevated secretion of il-6, tnf, ccl5/rantes, and ccl3/mip1 alpha. 26175939_1 low levels of mir-93 were associated with high levels of mmp3 and vegfa protein, indicating a potential role of mir-93 in regulating the expression of mmp3 and vegfa. 26175939_2 these results indicate that mir-93 targets the 3'-utr of mmp3 and vegfa mrnas, leading to down-regulation of mmp3 and vegfa protein. 26175939_3 these data indicate that mir-93 suppresses the expression of mmp3 and vegfa through binding to seed sequence at the 3'-utr of mmp3 and vegfa mrna. 21156648_1 furthermore, we identified a novel direct target of mir-7, the mrna for associated cdc42 kinase 1 , with the expression levels of mir-7 and ack1 being inversely correlated in human schwannoma samples. 21156648_2 together, these data indicate that the ack1 3'-utr is a specific target of mir-7 and that all 3 predicted mir-7-bindsg sites in the ack1 mrna 3'-utr are likely to be specific and direct target of mir-7 with a marked total effect on expression. 21156648_3 we next examined the effect of mir-7 on the endogenous mrna and protein levels of ack1. 21156648_4 elevated mir-7 levels in a mouse schwannoma cell line, nf2s-1, also produced a marked reduction in the protein levels of ack1, pak1, and egfr . 21156648_5 taken together, our data suggest that ack1 and pak1 are especially important target of mir-7 in schwannoma cell growth. 21156648_6 no significant correlation was found between mir-7 downregulation and egfr mrna upregulation , suggesting that in schwannoma samples not all mirna-mrna interactions result in degradation of mrna. 21156648_7 these results show that mir-7 is a major regulator in schwannoma growth by regulation of ack1 and pak1 expression. 26820128_1 these results suggested that pik3r3 is a target gene of mir-152 in crc. 26348153_1 mir-223-5p and -3p could negatively regulate the expression of sema3a and stat3, respectively22 ; and 3 sema3a and stat3 both contribute to inflammatory response29,30,31,32. we therefore speculated that the presence or absence of mir-223 in mscs might affect cellular levels of sema3a and stat3, which were consequently incorporated into exosomes at different concentrations. 26348153_2 put together, these results indicate that wt-exosomes could deliver mir-223 to the myocardium and consequently, inhibit the expression of sema3a and stat3, two bona fide targets of mir-223; whereas mir-223-ko exosomes could deliver sema3a and stat3 proteins to the myocardium. 26431674_1 mir-17 directly targets ccnd1 in metastatic breast cancer. 26431674_2 mir-17 could directly target 3'-utr of ccnd1 mrna. 26252200_1 further study by luciferase reporter assay demonstrated that mir-24 could directly target carma3. 26252200_3 mutation of the mir-24-binding site in the carma3 3'-utr abolished the effect of mir-24, which suggested that carma3 was directly and negatively regulated by mir-24. 21930776_1 we identified arpc3, a component of the arp2/3 actin nucleation complex, as a bona fide target for down-regulation by mir-29a/b. 21930776_2 furthermore, we demonstrate that mir-29a/b directly target the mrna encoding for arpc3, a subunit of the arp2/3 actin nucleation complex . 21930776_3 here, we propose that the role of mir-29a/b is to modulate the activity of the arp2/3 complex by targeting the regulatory subunit arpc3 , thus maintaining flexibility in neuronal net- works. 21930776_4 the aforementioned data demonstrate that arpc3 levels are directly regulated by the targeting of mir-29a or -29b to the identified 3'-utr mre. 26802132_1 we identified arc as a mir-223 downstream target to mediate the function of mir-223 incardiac hypertrophy. 26802132_2 in this study, we show that heart-related circrna directly binds to mir-223 and acts as an endogenous mir-223 sponge to inhibit mir-223 activity, which results in the increase of arc expression, a target for mir-223. 26802132_3 further, we attempted to investigate whether mir-223 and arc are functionally related in hypertrophy and observed that the inhibitory effect of mir-223 knockdown on hypertrophic responses was decreased in the absence of arc , indicating that mir-223 exerts its effect through arc. 26802132_4 these data indicate that arc is a downstream target of mir-223 in regulating cardiac hypertrophy and heart failure. 26404566_1 cxcr4 is a novel direct target of mir-622 in hepatoma cells. 26771516_1 mir-1303, which function is not defined yet, is found to negatively regulate mycobacteria-induced atg2b protein production, ultimately down-regulate mycobacteria-induced autophagy. 26771516_2 we herein show that mir-1303, a mirna which function is not yet defined, targets atg2b and ultimately regulates mycobacteria-induced autophagy. 26771516_3 together the results indicate that mir-1303 binds to putative target sites on atg2b and represses the translation of atg2b. 26771516_4 we hereby show that atg2b can be targeted by a novel mirna, mir-1303, in human primary macrophages. 23249809_1 interestingly, we found that the rsv nonstructural genes ns1 and ns2 antagonized the upregulation of let-7i and mir-30b. 22363537_1 the presence of the mir-338 expression vector significantly reduced luciferase activity by 15% in b35 cells as compared to null-vector co-transfected neurons, indicating that 39utr of aatk mrna is targeted by mir-338 . in contrast, luciferase levels did not change significantly when the mir-338-5p mimic was co-transfected with this reporter plasmid, indicating that rat aatk mrna is specifically targeted by mir-338-3p. 22363537_2 collectively, these results suggest that mir-338-3p has the capacity to modulate rat aatk mrna levels. 18535243_2 xci, tsix is downregulated on xi as xist upregulates >30-fold. 18535243_3 on xa, tsix persists as xist is downregulated. 16166262_2 both mutants completely abolish the interaction between mir-15a and mir-16-1 and the 3'utr of bcl2 . 16166262_4 whereas in normal cd5+ lymphoid cells the levels of both mirnas were high and the bcl2 protein was expressed at low levels, in the majority of leukemic cells both mir-15a and mir-16-1 were expressed at low levels and bcl2 was overexpressed . 16166262_6 thus, in cll cases we observed a concordant down-regulation of mir-15a and mir-16-1 and overexpression of bcl2 protein. 16166262_7 this result demonstrates that mir-15a and mir-16-1 do not affect mrna stability and regulate bcl2 expression at the posttranscriptional level. 20889678_1 silencing mir-106a by transfection with the mir-106a inhibitor suppressed cell proliferation, induced cell cycle arrest and apoptosis, and inhibited anchorage-independent growth and tumor growth in nude mice. 20889678_2 bioinformatic analysis showed that tumor suppressor rb1 is one of predictive targets of mir-106a. 22446044_1 additionally, we confirmed that chicken hoxa1 is a mir-10a targetgene, suggesting a conserved role for mir-10a in the regulation of hematopoiesis across vertebrates. 22446044_2 in the present study we validated hoxa1 as a mir-10a targetgene in chickens . 22446044_3 taken together, these studies suggest a conserved function of mir-10a in vertebrates in the maintenance of hematopoietic stem cell populations through the targeting of hoxa1 and possibly itgb1. in addition, the involvement of mir-10a in the regulation of hoxa1 in hematopoesis is likely conserved in avian species. 26314198_1 luciferase reporter assay results showed that cdk2-associated cullin 1 was a direct target of mir-106a* in ec. the results of western blot and qrt-pcr showed that cacul1 mrna and protein significantly increased in ec tissues compared with their normal tissues . 26314198_2 it indicates that mir-106a* can inhibit cacul1 expression through its binding sequences at the 5'utr. 26853553_1 then, we mutated these binding sites by site-directed mutagenesis and demonstrated that mutations on the binding sites for mir-141 and mir-22 successfully abolished the previous suppressive effect , suggesting that mir-141 and mir-22 did target h19 by inducing transcriptional suppression rather than directly degrading h19 rna transcript. 26853553_2 collectively, our results pinpointed a functional role of h19 as a natural mirna decoy for mir-141 and mir-22. 19571673_1 wrap53 is a natural antisense transcript of p53 that regulates endogenous p53 mrna levels and is furthermore required for induction of p53 protein by targeting the 5'untranslated region of p53 mrna. 19571673_2 this could be due to a transient interaction between the complementary transcripts resulting in a permanent modification of the p53 mrna that protects it from degradation even after detachment of the wrap53 mrna. 25566965_1 moreover, overexpression of mir-192 significantly induced apoptotic death in bladder cancer cells, increased the levels of p21, p27, and bax, and decreased the levels of cyclin d1, bcl-2, and mcl-1. 23392577_1 a luciferase reporter assay assessed the mir-130b targeting potential of dicer1. 23392577_2 dicer1 is a mir-130b target gene in human endometrial cancer cells. in our study, overexpression of mir-130b empower cell motility through targeting dicer1, meanwhile, increased cell viability and reduced cell death and apoptosis. 22179486_2 oligo microarray analysis suggested that the mesoderm development candidate 1 gene was a target gene in mir-574-3p transfectants. 23318420_1 let-7 targets a variety of molecules involved in differentiation and early embryogenesis, and mir-200 directly regulates e-cadherin transcriptional repressors, zeb1 and zeb2. 23318420_2 the expression pattern of mir-200b/c was coincident with the elevation of the zeb1 level. 23318420_3 we transfected let-7b/d/g and mir-200b/c into mcf-7 cells and demonstrated that forced expression of these exogenous mirnas dramatically restored the expression of e-cadherin and downregulated the levels of zeb1, snail and fibronectin . 23318420_4 these data indicate that stat3 upregulates the expression of hmga2 and zeb1 at the post-transcriptional level by suppressing let-7 and mir-200. 20404570_1 we found that in both a549 and h1299 cells, protein levels of prkce were significantly reduced by mir-129 . 20404570_2 3'utr luciferase reporter with wild type 3'utr of prkce was significantly suppressed by mir-129, but not by mir-410 . 20404570_3 this indicated that prkce is a direct target of mir-129. 25753579_1 importantly, lin28b and let-7 can function as a molecular switch, in that let-7 targets lin28b mrna for degradation and lin28b functions to sequester pre-let-7 from processing to functional mirna . 25754817_1 mir-5100 translationally repress rab6 by targeting specific sequences in the 3'-utr of rab6. 25754817_2 these results indicate that mir-5100 negatively regulates rab6 by targeting a specific site in the rab6 3'-utr. 25754817_3 these data suggest that exogenous expression of rab6 compromises the ability of mir-5100 to promote cell growth in vitro and in vivo, which is consistent with its role as a functional target of the mir-5100 pathway. 21329689_2 tlr4 protein was significantly down-regulated by transfection with mir-146a mimics, but was only slightly reduced by mir-146a inhibitors in oxldl-stimulated microphages . in this study, with sustained oxldl stimulation, tlr4 was up-regulated with a decrease in expression of mir-146a. 21329689_3 in contrast, tlr4 was down-regulated by over-expression of mir-146a. 21317190_1 this work shows that hsa-mir-125a-5p, a microrna expressed in human liver, is able to down-regulate the expression of hbv s gene thus reducing the amount of secreted hbsag. 23403649_1 in this study, hybrid-pcr screening was used to identify target genes and dual luciferase reporter assay was used to evaluate the binding effect of hcmv-mir-ul148d to the 3' untranslated region of iex-1. 25116893_2 moreover, we showed that the mir-125a mimic downregulated the antiapoptotic bcl2 protein and upregulated caspase 3, suggesting that these two proteins represent molecular targets for mir-125a. 26761212_1 furthermore, we demonstrated that arhgdia is a potential target of mir-151-5p and mir-16 in gliomas. 26761212_2 arhgdia is a target mrna of pcbp2 and is also a target of mir-151-5p/mir-16 in gliomas. 26761212_3 we demonstrated that arhgdia is a potential target of mir-151-5p and mir-16 in gliomas. 26089375_2 encompassed within the validations were the novel reciprocal mirna-rna pairings mir-133a/mcl1, mir-96/foxo3a, mir-513c/stat1, mir-34a/ppp2r2a, mir-145/itpr2 and mir-145/mkk4 . 26232047_1 furthermore, the luciferase reporter assay demonstrated that lamp2 and hexb were the direct targets of mir-207 and mir-352, respectively. 26232047_2 these results suggested that mir-207 and mir-352 down-regulated the expression of lamp2 and hexb proteins. 26232047_3 furthermore, in vitro, the luciferase reporter assay suggested that mir-207 and mir-352 down-regulated the lamp2 and hexb proteins in primary cortical neuronal cells. 20886090_1 mir-103 is part of the g1/s transition regulatory network, which targets ccne1, cdk2, and creb1 during igf-1 stimulated proliferation. 20886090_2 we explored whether mir-103 could affect the identified gene targets through interaction with the mrna 3'-utr. in hek293 cells, co-transfection with mir-103 mimic could repress the luciferase activity generated by luciferase vectors containing the mrna 3'-utrs of ccne1, cdk2, creb1 of human and mouse origin in a dose dependent manner, clearly indicating direct binding between the mirna sequence and the genes. 20886090_3 to examine whether the mir-103 targets are involved in igf-1 stimulated mouse intestinal cell proliferation, immunoblotting analyses were performed on the crypt cells before and after igf-1 treatment. 20886090_5 mir-103 directly binds and represses ccne1, cdk2, and creb1 mrna through 3'-utr. 18417445_1 moreover, we provide evidences of mir-221 and mir-222 capabilities to regulate two distinct but functionally convergent pathways of melanocyte transformation through the cyclin-dependent kinase inhibitor 1b on one side and c-kit and its downstream genes on the other. 26499439_1 mir-107 suppresses mitochondrial hadha levels in hepg2 cells. 26870225_1 previous studies have reported that akt may be a potential target of mir-147. 26870225_2 demonstrates that mir-147 expression repressed the phosphorylation of akt, p70s6k and 4e-bp-1 in mda-mb-231 cell, but appeared to have no effect on the total level of these proteins. 26870225_5 generally, the effect of mir-147 on akt/mtor pathway was analogous to that of sirna directed at akt. 20691260_1 overexpression of mir-204 in caki-2 cells leads to downregulation of tr-beta1 mrna and protein. 20691260_2 transfection with mir-204 precursor resulted in a large induction of mir-204 expression which was followed by ~ 42% decrease of tr-beta1 mrna expression and ~ 35% decrease of dio1 mrna expression when compared with scrambled control. 9018369_1 electrophoretic mobility shift experiment indicates that 7sk rnp participates in transformation-dependent deregulation of the c-myc gene by activation of two c-myc minor promoters. 26762410_1 finally, mef2d is a direct target of mir-19, which was found to be decreased in gastric cancer clinical specimens. 26762410_2 the above results demonstrated that mef2d is the direct target of mir-19. 25337209_1 luciferase reporter assays and western blot further confirmed the direct interaction of mir-423-3p with adipor2. 25337209_2 finally, we further confirmed that the directly interaction between mir-423-3p and adipor2 by western blotting. 25337209_3 the novel finding in our study is that adipor2 was identified as a target for mir-423-3p . 26361793_1 our luciferase reporter and western blotting assays demonstrate that both errfi1 and fzd7 are direct targets of mir-126 . 26361793_2 errfi1, spred1 and fzd7 are critical direct targets of mir-126. 19137007_1 mir-143 is mirna that targets kras. in colon cancer tissues, there is an inverse correlation between kras protein and mir-143 expression. 19137007_3 apart from kras, it was identified erk5 and dnmt3a as direct targets of mir-143. 26297956_1 these results indicated that mir-145 was significantly downregulated and adam17 was upregulated in npc.thus, mir-145 may be a tumor suppressor in npc and may have a negative correlation with adam17. 26297956_3 after transfecting cne-1 and cne-2 cells with mir-145 mimic or nc, adam17 mrna and protein expression was determined through qrt-pcr and western blot analysis, respectively. 26297956_4 transfection of mir-145 mimic into cne-1 and cne-2 cells significantly downregulated the protein expression of adam17 . 26307612_1 we also identified that trove2 is a novel target of mir-128 by the luciferase reporter system. in this study, we evaluated the expression profile of mir-128 in the different grades of astrocytomas and identified that trove2 as a new target for mir-128 in astrocytoma tissues. 26307612_2 these results strongly suggested that mir-128 regulates the expression of trove2 directly. 26307612_3 here, we identified that trove2 as a novel target of mir-128 by luciferase reporter system and western blot. 23233482_1 bioinformatics analysis and luciferase reporter assay revealed that mir-145 directly targeted the 3'-untranslated region of ets1 mrna. 23233482_2 overexpression or knockdown of mir-145 responsively altered both the mrna and protein levels of ets1 and its downstream genes, matrix metalloproteinase -1 and -9, in gastric cancer cell lines sgc-7901 and mkn-45. 23233482_3 these results show that mir-145 suppresses ets1 expression via the binding site in the 3'-utr, thus inhibiting the invasion, metastasis, and angiogenesis of gastric cancer cells. 23233482_4 overall, these results showed that mir-145 considerably inhibited ets1 expression through posttranscriptional repression. 22064828_1 sirt1 and bcl2 are two major target genes suppressed by mir-34a. in all, the only sharp inverse relationship detected at early adult life between mir-34a and its target, sirt1, is observed in plasma. 26708214_1 rasa1 was validated as a target of mir-335 that was downregulation in crc. 26708214_2 we show that to acquire such proliferation capacity, mir-335 targets the ras p21 protein activator 1 , which acting as a suppressor of ras function. 26708214_3 moreover, mir-335 could not decrease the luciferase activity of mutant rasa1 in the mir-335 binding site , indicating mir-335 targets the specific region on rasa1 3 ' utr. 26708214_4 our results confirmed that rasa1 was a direct target of mir-335. 21701775_2 molecular target identification of these mirnas showed that transgelin 2 and purine nucleoside phosphorylase were regulated by mir-1 and mir-133a. 23606743_1 mir-128a was found to regulate the target genes involved in insulin signaling, which include insr , irs1 and pik3r1 at both the mrna and protein level. 23606743_2 overexpression of mir-128a in myoblasts inhibited cell proliferation by targeting irs1. 23606743_5 these results indicated that overexpression of mir-128a in myoblasts attenuated cell proliferation by suppressing the levels of irs1 and phosphorylated akt. 23606743_6 our findings have highlighted mir-128a function in myogenesis, and identified novel muscle-enriched target gene, irs1. 21159845_1 direct interaction with thrb was shown for mir-21 and mir-146a. 21159845_4 we showed inhibition of luciferase activity by mir-21 and mir-146a but not by mir-181a and mir-221 . 11461923_1 the refolded hok mrna is translatable but can also bind the inhibitory sok antisense rna. 11461923_3 a coherent model predicts that during transcription hok mrna must be refractory to translation and antisense rna binding. 11461923_4 the metastable structure reduces the rate of sok rna binding and completely blocks hok translation in vitro. 23504349_3 fasl, timp3 and reck are direct targets of mir-21. 26450370_1 in this study, we identified mir-145 as an mirna that targets cbfb. 26450370_2 we also demonstrated that mir-145 inhibits osteoblastic differentiation in cooperation with mir-34c, which targets runx2. 26450370_3 mir-34c inhibits osteoblast differentiation by regulating runx2 expression . 26450370_4 these results indicate that mir-145 and -34c cooperatively inhibit osteoblast differentiation through cbfb and runx2 protein expression. 23410941_2 inactivation of mir92a stabilizes nog3 mrna, leading to repression of bmp signaling and abnormal behaviors of chondrogenic progenitors. 23410941_3 in contrast, ectopic expression of mir92a duplex decreases nog3 mrna levels and, as a result, derepresses bmp signaling and promotes cell apoptosis. 25152372_2 ectopic expression of mir-133a in gastric cancer cell lines bgc-823 and sgc-7901 markedly inhibited the protein translation of cdc42 and remarkably repressed the activation of pak1 kinase . 25152372_3 and the results also prove that cdc42 is a target of mir-133 in gastric cancer. 21228099_1 together, these data indicate that both dcx and chrdl-1 are novel, bona fide targets of mir-134. 21228099_2 the apparent, regional enrichment of mir-134 and its target dcx in the cp would argue against a strong posttranscriptional regulatory interaction in vivo. 21228099_3 thus, under in vitro conditions, elevated mir-134 levels can promote npc proliferation in a manner that can be rescued by either chrdl-1 or dcx co-expression and by enhanced cell death and enhanced senescence, respectively. 21228099_4 importantly, co-expression of either dcx or chrdl-1 cds with pre-mir-134 was sufficient to rescue mir-134-搃nhibited cell migration , suggesting that both proteins may regulate npc migration in vitro. 21228099_5 these results suggested that pre-mir-134 modulates dendritic maturation in response to exogenous bmp-4 application, in part, through posttranscriptional modulation of the bmp antagonist, chrdl-1 . 26317550_2 aldh1a1, pir and pdcd4 were all expressed at lower levels in cl16-mir-155-derived tumors than cl16-ctrl-derived tumors. 26317550_3 immunocytochemical staining of nm-2c5 and cl16 cells showed that aldh1a1, in contrast to cl16, was not expressed in nm-2c5 , and pir showed weaker expression in nm-2c5 than in cl16, correlating with high mir-155 expression in nm-2c5 . 19771525_2 the lack of mir-17-3p expression correlated with an increase in vimentin synthesis and tumorigenicity. 19771525_3 stable expression of mir-17-3p in the m12 subline reduced vimentin levels 85% and reverted growth to organized, polarized acini in lrecm gels. in vitro motility and invasion assays suggested a decrease in tumorigenic behaviour, confirmed by reduced tumor growth in male athymic, nude mice dependent on mir-17-3p expression. 26408907_1 mir-761 suppresses mitochondrial biogenesis of c2c12 myocytes by targeting the 3' -utr of peroxisome proliferator-activated receptor gamma coactivator-1 . 26408907_2 mir-761 directly targets 3' -utr of pgc-1a. 26408907_3 mir-761 suppresses mitochondrial biogenesis of c2c12myocytes by targeting the 3' -utr of pgc-1a mrna. 25925429_1 we used mir-1 as a positive control, which was as assayed by the down-regulation of the ptk9 target gene . 25925429_2 transfection of mir-1 also showed significantly higher troponin t expression because mir-1 also regulates proliferation and differentiation of myoblast cells by targeting the transcription of hdac4 . 22739938_1 moreover, we identified the cyclin d1 gene as a novel direct target of mir-138. in consistent with the knocked-down expression of ccnd1, overexpression of mir-138 inhibited cell growth and cell cycle progression in npc cells. 22739938_2 furthermore, ccnd1 was widely upregulated in npc tumors, and its mrna levels were inversely correlated with mir-138 expression. 22739938_3 taken together, our findings suggest that mir-138 might be a tumor suppressor in npc, which is exerted partially by inhibiting ccnd1 expression. 22739938_4 collectively, these in vivo studies demonstrated that mir-138 could downregulate ccnd1 and inhibit the tumorigenicity of cne2 cells in nude mice. 23175432_1 these results suggested that tle1 is a direct target of mir-657 in hcc cells. 23175432_2 using western analyses, we further found that tle1 protein expression levels were significantly reduced by mir-657 transfection in hep3b, huh7, cl-48, and hepg2 cells . 23175432_3 taken together, these results suggested that tle1 is a direct target of mir-657 in hcc cells. 23175432_4 our observations suggest that tle1 may be frequently downregulated in hcc samples and the reduction may be caused by overexpression of mir-657. 23175432_5 taken together, these results showed that mir-657 activated nf-jb, and the activation is likely mediated by tle1. 23175432_6 therefore, our data suggest that mir-657 contributes to hepatocarcinogenesis through tle1. 23519696_1 these results demonstrate that overexpression of mir-144 results in decreased abca1 protein levels in both mouse and human hepatocytes, suggesting that the mechanism may be conserved across these species. 23519696_2 it is also interesting to note that mir-144 regulates abca1 largely at the protein level. 21358675_1 mir-451 directly target rab14 gene by interaction with the 3-utrs. 21358675_2 these data indicated that mir-451 could directly targetrab14 in nsclc cells by interaction with the 3'-utrs of rab14 gene. 21358675_3 notably, the tumor suppressor effects of rab14 knockdown mediated by sirna were similar to those of ectopic mir-451 expression, suggesting that rab14 targeting might be a mechanism of the tumor suppressor function of mir-451 in nsclc cells. 21358675_4 taken together, our results showed that restoration of rab14 expression could partially rescue the tumor suppressor function of mir-451 in nsclc cells, which further showed that rab14 might be potentially involved in mir 451-regulated tumor suppressing function. 21358675_5 therefore, higher expression of rab14 protein was negatively associated with downregulated mir-451 in nsclc tissue samples, suggesting that rab14-mir-451 interaction might be biologically significant in human nsclc 25340791_1 bioinformatics analyses indicated that mir-30c might target several other key mrnas, including metastasis-associated genes metadherin and high-mobility group at-攈ook 2 . 25340791_2 we found that there are four binding sites for mir-30c in mtdh 3'-utr and one binding site in hmga2. 25340791_3 ectopic expression of mir-30c led to significantly decreased levels of mtdh and hmga2 in h1299 and a549 cells. 25340791_4 taken together, these data suggested that mtdh and hmga2 are direct target genes for mir-30c in lung cancer. 25340791_5 these data strongly suggest that fhit and mir-30c inhibit metastasis through targeting the metastasis-related genes, mtdh and hmga2. 23326547_1 a dual luciferase reporter assay confirmed that beclin-1 was a target gene of mir-30a. in summary, these findings suggest that beclin-1 was a target gene of mir-30a. in additional experiments, we further demonstrated that beclin-1 is the target gene of mir30a, and that mir-30a binds with the 3'utr of beclin-1. 18818396_1 using a luciferase reporter assay, we found that mir-15a directly bindhe 3'-utr of c-myb mrna. 18818396_2 together, these results demonstrate that mir-15a decreased c-myb protein expression by inhibiting mrna translation, not by targeting c-myb mrna for degradation. 18818396_3 the resulting constructs, pbub1/myb3u/mir-15a1, pbub1/myb3u/ mir-15a2 and pbub1/myb3u/ mir-15a1,2 were cotransfected together with mir-15a into hek293 t cells. 26586336_1 inthisstudy, we identified hoxa9 as a target gene of mir-196b and determined that the mechanism of mir-196b-mediated emt and invasion processes involves the regulation of hoxa9 expression in nsclc cells. 26586336_2 this result indicated that the 3 ' utr of hoxa9 is directly regulated by mir-196b. 26586336_3 these results suggest that hoxa9 is direct target of mir-196b in nsclc cells. 26586336_4 therefore, our data provide evidence suggesting that hoxa9 is controlled by mir-196b in nsclc cells 26612211_1 mir-124 negatively regulated notch1 signalling by targeting jag1. in addition, mir-124 can regulate notch1 signalling by targeting notch ligand jagged1 in gc cells. 26612211_2 these results suggest that mir-124 targeted the 3 ' utr region of jag1 and inhibited jag1 expression, thereby negatively regulating the notch1 signalling pathway. 26719710_1 it showed there was significant binding between mir-125a-5p and wt naif1 firefly luciferase vector, confirming that naif1 was the direct target of mir-125a-5p. 26719710_2 in addition, the result of western blot showed that the protein expression levels of naif1 and caspase-3 were also significantly upregulated by mir-125a-5p down-regulation in du145 and vcap cells 26749280_1 mir-378 directly targets and inhibits runx1 in human breast cancer cells 18708351_1 the expression of mir-221 and mir-222 was also significantly elevated in her2/neu-positive primary human breast cancer tissues that are known to be resistant to endocrine therapy compared with her2/neu-negative tissue samples. 18708351_3 the protein level of the cell cycle inhibitor p27 , a known target of mir-221/222, was reduced by 50% in oht cells and by 28-50% in mir-221/222-overexpressing mcf-7 cells. 22864815_1 luciferase reporter and invasion assays revealed that c1qtnf6, sparc, and col4a2 were targeted by mir-29b and that the degradation of any one of these mrnas could promote invasion in mcf-7 cells. 22864815_2 c1qtnf6, col4a2, and sparc showed quenching percentages lower than 50%, confirming that the predicted targetsequences were specifically responsible for the mir-29b sensitivity of these 3'utrs. of these five candidate targetgenes, c1qtnf6, sparc, and col4a2 were confirmed by luciferase analysis to contain 3'utrs that are directly targeted by mir-29b and should be considered target of this mirna. 25775145_1 the results of the luciferase reporter assay revealed that mir-181b negatively regulated aid and ifn-alpha. 25775145_2 these results suggested that both aid and ifn-alpha 17 have the potential to be the direct targets of mir-181b. 19544458_1 this mir-92b-mediated inhibition was eliminated when the seven-nucleotide mir-92b seed binding sequence was deleted . 19544458_2 these results together suggest that p57 is one of the direct target of mir-92b. of these 16 genes, cdkn1c had the highest pictar score. 19544458_3 these results together suggest that p57 is one of the direct target of mir-92b, and that p57 downregulation by mir-92b likely contributes to the smaller fraction of cells in g1 phase characteristic of human es cells. 24973144_3 notably, we showed that syt1 and atg9a are mir-34a targets in neural differentiation context, markedly decreasing after mir-34a overexpression. 24973144_4 syt1 overexpression and rapamycin-induced autophagy partially rescued the impairment of neuronal differentiation by mir-34a. 25801675_1 luciferase reporters containing the 3'utr of trpc6 or a mutated 3'utr of trpc6 in the mir-26a binding site were constructed and transfected into 293t cells . 25801675_2 we found that mir-26a markedly inhibited the luciferase activity of the vector containing the wild-type binding site, whereas the mir-26a inhibitor increased luciferase activity . 25801675_3 moreover, transfection of mir-26a failed to affect the luciferase activity of the reporter carrying the mutated mir-26a binding site. 25801675_4 overexpression of mir-26a inhibited the ox-ldl-induced trpc6 upregulation . 25801675_6 these findings indicate that trpc6 acts as a downstream effector of mir-26a in haecs. 25139024_1 mir-136 directly targets e2f1 in glioma cells by interaction with the 3'-utrs to suppress e2f1 expression. 22293115_1 luciferase reporter assay confirmed the ability of mir-125b to dramatically suppress bcl-2 transcription, suggesting that bcl-2 is a targetgene for mir-125b. 22293115_2 in contrast, the luciferase activity of the mutant reporter in the presence of phrs-1cla-mir125b was almost unaffected , indicating that mir-125b may suppress bcl-2 gene expression through its binding sequence at the 3' utr of bcl-2. 22293115_3 these data were confirmed by ihc staining of xenograft tumor tissue, which showed that bcl-2 protein level was inversely correlated with mir-125b expression . 22293115_4 taken together, these results suggest that mir-125b can promote cancer cells apoptosis by directly inhibiting the expression of bcl-2. 23886710_1 moreover, bioinformatic analysis combined with luciferase reporter assay, and western blot validated that mir-145 negatively regulated sp7 expression. in this study, we characterized mir-145, a novel down-regulated mirna , and investigated its effects on osteoblast differentiation. 23886710_2 we identified sp7 as its target, proposing a regulatory mechanism in which mir-145/sp7 controls osteoblast differentiation. 23886710_4 these results suggested that mir-145 could negatively regulate sp7 expression. 23886710_5 these results suggested that mir-145 suppressed osteogenic differentiation of c2c12 cells partially by inhibiting sp7 expression. 25742789_1 murine mir-128, mir-134, and mir-330 directly target and inhibit mmp3, mmp10, and mmp13, respectively. 25742789_2 furthermore, the expression levels of mir-128, mir-134, and mir-330 correlated negatively with those of mmp3, mmp10, and mmp13 22895360_1 mir-145 targets a binding site of myosin va. the luciferase reporter assay for mouse myo5a confirmed an actual target site for mir-145. 22895360_3 parallel to the mouse, we were able to show that the first binding site of myo5a mediates the interaction between mir-145 and myova 3'-utr. 22895360_4 a luciferase reporter assay demonstrated direct targeting of myo5a by mir-145 in mouse and human melanocytes. 22895360_5 mir-145 regulates myo5a expression by targeting the 3- -untranslated region of myo5a messenger rna. 22265971_1 therefore, mir-195-5p is a novel and also the first identified mirna that target glut3, and the aberrant decreased expression of mir-195-5p and consequent glut3 up-regulation may contribute to bladder carcinogenesis. 22265971_3 2b, the expression of mir-195-5p was strikingly down-regulated in t24 cells compared with that in huc cells, suggesting an inverse correlation between mir-195-5p and glut3 expression in t24 cells. 22265971_4 these data demonstrate that mir-195-5p directly inhibits glut3 expression by targeting glut3 3'-utr. 22265971_5 therefore, mir-195-5p may decrease glucose uptake of bladder cancer cells by down-regulating glut3. 25605244_1 these findings suggest that up-regulation of mir-125b or targeting sema4c could serve as novel approaches to reverse chemotherapy resistance in breast cancers. 25605244_2 taken together, these findings suggest that mir-125b specifically targets the 3'-utr of sema4c and subsequently inhibits its expression. 23315007_2 these target genes, besides pik3cb, were shown to be significantly up-regulated by qrt-pcr assay, which further suggested that pik3cd, ppp3ca, ppp3r1, casp3, il1a could be regulated by mir-384-5p. 26893711_1 overall, these results strongly indicate that cyld is a direct target of mir-362-5p in breast cancer cells. 26137169_1 therefore, in the current study vim was selected to investigate whether mir-134 may target vim in skov3-tr30 cells. 26137169_2 combined with luciferase reporter assay , the results indicate that vim is likely to be direct target of mir-134 and that vim protein was regulated at the post-transcriptional level in skov-tr30 cells. 19855844_2 luciferase activity of the 3- utr erk-luc construct was decreased in the presence of mir-143, whereas luciferase activity of mutated -luc construct was not affected, suggesting that mir-143 modulate erk5 expression through binding to erk5-3'-utr . 19855844_3 finally, analysis of erk5 protein level by immunohistochemistry indicated that erk5 expression was decreased in presence of mir-143 in lncap and c4-2 tumors . 21841313_1 here, we demonstrate that mir-107 negatively regulates the tumor suppressor mirna let-7 via a direct interaction. 21841313_2 taken together, these results indicate that mir-107 interacted with let-7 and suppressed let-7-mediated gene regulation. 21841313_3 these observations support the direct interaction between mir-107 and let-7. 21841313_4 these results indicated that mir-107 modulated the stability of let-7 and therefore had an impact on its ability to regulate gene expression. 21841313_5 together with the above information, this suggests that mir-107 could directly bind and suppress all let-7 family members. 26589421_1 the luciferase reporter assay showed that atp6v1a and il13ra1 were targets of mir-143 and that mir-26 regulates binp3l and arl6ip6. 22751012_1 we demonstrated that mir-125a target dies1 and regulates its expression in escs. 22751012_2 dies1 is a target of mir-125 in mouseescs. 22751012_3 mir-125a and mir-125b directly regulate dies1 expression in escs by targeting its 3'-utr. 22751012_4 we first demonstrated that dies1 is a direct target of mir-125a in mouseescs. 22751012_5 figure 1.mir-125a and mir-125b directly regulate dies1 expression in escs by targeting its 3'-utr. 22751012_6 altogether, these results indicate that the effects of mir-125a overexpression on esc pluripotency are mostly mediated by dies1. 22751012_7 overexpression of the 2 pre-mirs confirmed the in silico prediction, resulting in a clear decrease of dies1 protein level , while dies1 mrna remained unaffected , indicating that inhibition of translation rather than mrna degradation is the main mechanism of dies1 regulation by mir-125. 22751012_8 conversely, the suppression of mir-125a and mir-125b resulted in the accumulation of dies1 protein , whereas its mrna was unchanged . 25394901_1 bioinformatics analysis predicted that the seed sequence of mir-218 binds to the 3- utr sites of brca1 at 212- 218 and 345- 351. to evaluate the extent of binding between mir-218 and the 3- utr region of brca1, mir-218 target reporter luciferase reporter assay was performed by evaluating the luciferase activity of hek-293 cells transfected with pmir-brca1 3'-utr plasmids and comparing this activity with that of cells transfected with control plasmids. 25394901_2 these results indicate that mir-200 regulates brca1 not at the level of rna stability but at its translation. 18716028_1 the effects of mir-377 on sod translation, and proteins were also evaluated. 18716028_2 in a luciferase assay in which the 3'-utrs of sod1 and sod2 were included in the pgl3r vector, mir-377, but not mir-143 as control, considerably reduced luciferase activity 23788640_1 fog2 expression is down-regulated in glomeruli of diabetic mice. in addition, the 3'-utr of fog2 is highly conserved in humans and mice. 23788640_2 therefore, we examined whether fog2 could also be down-regulated by mir-200b/c under diabetic conditions in mmc. 23608226_1 taken together, we conclude that ebv-encoded mir-bart20-5p inhibits t-bet translation with secondary suppression of p53 in invasive nasal nk/t-cell lymphoma. 23349340_1 interestingly, lygdi was discovered as a new target gene of mir-34a, and downregulation of lygdi promoted rac1 activation and membrane translocation, resulting in cell apoptosis. 26231042_1 the microrna mir-34a inhibits prostate cancer stem cells and metastasis by directly repressing cd44. in figure 4, liu and colleagues present data supporting the hypothesis that cd44 is a target of mir-34a. 26231042_2 tumors with exogenous mir-34a showed reduced levels of cd44 expression , and mutation of two putative mir-34a binding sites in the cd33 3- utr partially abrogated signal repression in a luciferase assay . 21544626_1 in a549 cells, mir-200b targeted the predicted binding sites in the 3'-untranslated region of vegf, flt-1, and kdr as revealed by a luciferase reporter assay. 21544626_3 fig. 2. down-regulation of vegf, flt-1, and kdr by mir-200b through direct targeting of 3'-utrs. 21544626_4 together, these results show that mir-200b and mir-200c down-regulate flt-1, kdr, and vegf at the protein level. 21544626_5 taken together, these data indicate that mir-200b directly regulates vegf, flt-1, and kdr through interaction with predicted binding sites in their 3'-utrs. 24586173_1 through biochemical assays and functional rescue analysis, we confirmed that mir-bart9 specifically inhibits e-cadherin to induce a mesenchymal-like phenotype and promote the migration of npc cells.a 24586173_4 through bioinformatics analysis and functional verification, we demonstrated that mir-bart9 directly repressed e-cadherin . 21071935_1 we then showed that mir-25 negatively regulated nox4 expression by directly targeting the 3' -utr by luciferase reporter assays. 21071935_2 these results further confirm nox4 to be a mir-25 target. 21071935_3 our results indicate that mir-25 as an endogenous gene silencing factor importantly contributes to the regulation of nox4 gene expression in dn. in summary, our results strongly indicate that mir-25 as an endogenous gene silencing factor importantly contributes to the regulation of nox4 expression and function in dn. 21366874_1 acsl1 was a target gene of mir-34a and mir-34c that became dysregulated in hepatic fibrotic tissues.these 21366874_2 results suggested that acsl1 is a direct target gene of mir-34a and mir-34c. 21366874_3 acsl1 is a direct target gene of mir-34a and mir-35c that become dysregulated in hepatic fibrotic tissues. 26459459_1 naip is a shared target of mir-145 and mir-1, but not mir-451 in hct116 cells. 19775284_3 mir-1 was up-regulated in mi, possibly due to the concomitant increase in srf, a transcriptional activator of the mir-1 gene, accounting for decreased kir2.1. 19775284_4 treatment with tanshinone iia prevented increased srf and hence increased mir-1 post-mi, whereas quinidine did not. 19775284_5 conclusions and implications: down-regulation of mir-1 and consequent recovery of kir2.1 may account partially for the efficacy of tanshinone iia in suppressing ischaemic arrhythmias and cardiac mortality. 18299284_1 hiv-1 tar element is the target of the viral transactivating tat protein, which is expressed during the course of hiv-1 infection and known to act at the rna level to enhance viral gene expression by >100-fold . 22908386_1 the data suggest mir-483 perturbs melatonin production by promoting destruction of the aanat transcript. 22908386_2 together, these findings are consistent with the conclusion that mir-483 acts early in life to suppress melatonin production by promoting degradation of aanat transcript; elevation of mir-483 under pathological or physiological circumstances might also suppress melatonin production. 23597480_1 contrary to this hypothesis, in this issue, wang et al. demonstrate that linc-ror actually functions as a microrna sponge to post-transcriptionally regulate the mrnas of the core transcriptional factors oct4, nanog, and sox2. 23597480_2 a direct competition for mir-145 binding occurs between linc-ror and the mrnas encoding the core tfs, and this tug of war regulates hesc self-renewal and differentiation . 23597480_3 the study by wang et al. strongly supports that linc-ror acts as a microrna sponge. 23597480_4 linc-ror modulates mir-145 levels, a sits overexpression diminishes endogenous mir-145 in self-renewing hescs and drastically delays the increase in mir-145 upon hesc differentiation. 22777896_1 we showed in a human hepatocyte cell line that mir-27b regulates the expression of several key lipid-metabolism genes, including angptl3 and gpam. 22777896_2 mir-27b inhibition also resulted in significantly increased cellular gpam levels . 22777896_3 inhibition of mir-27b increases cellular gpam and secreted angptl3 protein levels. 22777896_4 after site-directed mutagenesis to eliminate the putative mir-27b site , mir-27b failed to knock-down firefly luciferase activity, indicating that the site is directly involved in mir-27b mediated regulation of gpam . 22751499_1 here, we report that the microrna mir-8 and its target u-shaped , a conserved microrna/targetaxis that regulates insulin signaling, are critical forecdysone-induced body size determination in drosophila together, these results indicate that ecr signaling regulates mir-8 and its target ush, in vivo. 22751499_2 these data raised a possibility that mir-8 and ush may be temporally and reciprocally modulated by ecdysone signaling during larval development, where most of the organismal growth occurs . 23338605_1 in our tested mirnas, lef1 and ikk-b , mmp16 , cdk6 , e2f3a and bmi-1 were shown to overexpressed when ad-trail-4mres were applied. 26464649_1 moreover, a recent study identified that mir-7 was reported to inhibit a549 cell growth by targeting bcl-2. 25496461_1 gain- and loss-of-function analysis suggested that under hypoxia, the increased expression of mir-98 led to the downregulation of cyp19a1 mrna and protein expression and that it may have contributed to a reduction in estradiol production. 25496461_2 these data suggest that the hypoxia-upregulated mir-98 could repress cyp19a1 expression via specific interaction with its target site in the 3'-utr of the cyp19a1 mrna. 25496461_3 overexpression of pre-mir-98 led to a substantial decrease in cyp19a1 protein levels, while the anti -mir-98 treatment partially restored normal cyp19a1 protein levels . 25496461_4 overall, these results suggest that mir-98 is a hif-1-regulated mirna that downregulates cyp19a1 expression in hypoxic cells; and the reduction in cyp19a1 expression may account, in part, for the reduction in e2 production in hypoxic cells. 24486107_1 mir-1 targets pik3ca and inhibits tumorigenic properties of a549 cells. 24486107_2 mir-1 overexpression led to downregulation of pik3ca protein, but not mrna by western blot and quantitative real-time pcr, respectively. 22822053_2 however, data analysis identi-fied 36 genes that were differentially expressed during infection in the presence of mirna mimics: decreased expression was observed for 26 genes, whereas 10 genes increased expression .examination of mirna abundance in human lung cell lines revealed endogenous mirnas, including mir-7, mir-132, mir-146a, mir-187, mir-200c, and mir-1275.gene 25550803_1 down-regulation of mir-181b promotes apoptosis by targeting cyld in thyroid papillary cancer. 25550803_2 western blot analysis indicated that downregulation of mir-181b results in the upregulation of cyld at protein levels. 25374067_1 ectopic mir-338-3p expression significantly suppressed the in vitro proliferation and colony formation of nsclc cells and enhanced apoptosis. of note, ectopic mir-338-3p expression significantly inhibited ras related protein 14 mrna and protein expression, and reduced luciferase reporter activity containing the rab14 3'-untranslated region through the first binding site. 26884465_1 these results indicate that mir-675-3p can target zo-1 and e-cad mrnas. 26254226_1 spred2 is a mir-210 target gene. 26254226_2 transfection of the mir-210 mimic and inhibitor into hasmcs significantly and dose-dependently influenced spred2 protein expression . 26499912_1 pten is a downstream target of mir-616 in hcc cells. in all, these data demonstrated that pten is a direct downstream target of mir-616 and mir-616 can inhibit the expression of pten by binding to its 3'-utr. 26620926_1 these results suggested that mir-181b binds directly to putative tgf-betar1 3'-utr regions, as predicted. 23531080_1 our study's results are consistent with mir-497 being a candidate tumor suppressor in neuroblastoma, through the direct targeting of wee1. 22940131_1 to further determine if mir-16-mediated enac expression is through nedd4 modulation, we monitored the expression levels of nedd4 in mir-16 overexpressed a549 cells and controls post-treated with 1 or 2 mm serotonin. 22940131_2 levels of nedd4 were slightly reduced in mir-16 transfected a549 cells post-treated with 2 mm serotonin when compared to controls .our 22940131_3 data suggest that mir-16 mediated upregulation of enac is independent of nedd4. 21862142_2 specific antagomirs against these mirnas substantially increased hiv-1 protein translation in resting cd4 cells. 21383058_1 mir-24 inhibits apoptosis and represses bim in mouse cardiomyocytes. 26503460_1 taken together, these data indicate that zeb2 is a target of mir-154. 23343627_2 among the five mirna hits, the only upregulated mirna in response to influenza infection corresponded to mir-146a.table 1. gene expression data for the 16 mir-146a target genes down-modulated after influenza infection. 23097559_3 furthermore, western blot analysis showed that over-expression of mir-18a suppressed the endogenous dicer1 expression in the npc cell lines hk1 and 5-8f, whereas blocking mir-18a resulted in upregulation of endogenous dicer1 expression . 23097559_4 these results supported the hypothesis that mir-18a executes an oncogenic effect on npc cells, at least partly, through downregulating the expression of dicer1. 23097559_5 the lentivirus-mediated knockdown of dicer1 reversed the effects of antogomir-18a, suggesting that mir-18a affected the expression of e-cadherin and k-ras through the regulation of dicer1 . 22139073_1 the direct targeting of hmga1 by mir-16 , and of hmga2 by let-7a and mir196ab was previously reported. 22139073_2 moreover, previous studies showed that mir-26a regulates hmga2 expression .taken 22139073_3 together, our data clearly demonstrate that both hmga proteins are direct targets of mir-15, mir-16, mir-26a, mir-196a2 and let-7a. 22319171_1 accordingly, the seed region of this version of mir-1304 presents perfect complementarity with its predicted target site region at the 3- utr ofenam and amtn . 22319171_2 as shown in figure 3a, a statistically significant reduction of the luciferase activity was observed for enam and amtn when cotransfected with the ancestral mir-1304 as compared with the modern mir-1304 . 17613256_1 rather,we found that host mir24 and mir93 could target viral large protein and phosphoprotein genes, and a lack of mir24 and mir93 was responsible for increased vsv replication in dicer1 cells. 26718330_1 to unveil the underlying mechanism of the disrupted angiogenesis mediated by mir-497, the expression of vegf in mcf-7 cells was measured by western blot analysis.the 26718330_2 result indicated that the overexpression of mir-497 reduced the protein level of vegf while the suppression of mir-497 revealed an opposite result under normoxic conditions. 26718330_3 to further investigate the underlying mechanism, the expression of the transcription factor hif-1alpha, which is responsible for vegf regulation, in mcf-7 cells was examined through western blot analysis.fig. 4 shows that the expression of hif-1alpha was decreased in the mcf-7 cells after being transfected with the mir-497 mimics, correlating with decreased vegf production. 26718330_4 vegf is the direct target of mir-497 and inhibits angiogenesis. 25203395_1 this indicated that cse transcripts represented a genuine target of the mir-30 family. 25203395_2 our data demonstrated for the first time that the mir-30 family was able to regulate h2s production by directly targeting cse. 25203395_3 as shown in figure 2c, all five members of the mir-30 family have one 8-bp conserved target site in the 3'-utr of cse. 25203395_4 this strongly led us to believe that the 3'-utr of cse could be a target of mir-30 family. 25203395_5 mir-30 suppresses cse expression at both mrna and protein levels, indicating that mir-30 regulates cse expression by promoting mrna degradation. 25203395_6 in conclusion, our study is the first to identify and validate cse as a target of the mir-30 family and to demonstrate the role of the mir-30 family in mi injury. 23733246_1 we show that microrna-128 directly targets mrna of suz12,a key component of prc2, in addition to bmi1, a component of prc1 that we previously showed as a target as well. 23733246_2 therefore, mir-128 suppression of suz12 expression is most effective when both target sites of the suz12 mrna are targeted. 23733246_3 in fact, here we report that mir-128 targets a component of prc2 as well: suz12. 26878873_1 thus, mir-193b may mediate some of its effects on chemosensitivity in kyse450 cells through the negative regulation of the stathmin 1 transcript. 21316776_1 mir-204 regulate cardiomyocyte autophagy induced by hypoxia-reoxygenation through lc3-ii. 26779627_1 in summary, these data suggest that mir-155 can directly target the 3'-utr of xiap. 21245045_2 analysis of manxyz mrna stability and translation in the presence and absence of sgrs indicate that manxyzis regulated by sgrs under stress conditions and when sgrs is ectopically expressed. 21245045_3 in vitro footprinting and in vivo mutational analyses showed that sgrs base pairs with manxyz within the manx coding sequence to prevent manx translation. 21868360_1 the mir-221/222-mediated reduction in e-cadherin abundance depended on their targeting of the 3' untranslated region of trps1 , which is a member of the gata family of transcriptional repressors. 21868360_3 a titration of mir-221/222 revealed a down-regulation of luciferase production for the trps1 wildtype 3'-utr but not the trps1 3'-utr mutant construct, confi rming that trps1 is highly likely to be a targetfor mir-221/222 in vivo. 21868360_4 we also observed a decrease in trps1 at the protein level upon transfection of cells with mir-221/222. 21868360_5 indeed, depletion of zeb2 by sirna blunted the ability of mir- 221/222 expression and trps1 depletion to up-regulate e-cadherin expression. 25000291_1 mpt64 protein from mycobacterium tuberculosis inhibits apoptosis of macrophages through nf-kb-mirna21-bcl-2 pathway.furthermore, the results provided strong evidence that bcl-2 up-regulation was positively controlled by mirna-21. 25000291_2 finally, nf-κb was identified as the transcription factor for mirna-21 using a chip assay. 20638779_1 the data reported here are the first to indicate that mir-27a plays an oncogenic role by targeting spry2 and modulating the malignant, biological behavior of pancreatic cancer cells. 20638779_2 these data indicated that spry2 carries a putative binding site for mir-27a and can be directly regulated by mir-27a. 20638779_3 furthermore, the overexpression of mir-27a in panc-1 and mia paca-2 cells may decrease spry2 level, promoting cell proliferation and migration. 20638779_4 this suggests that mir-27a may be involved in the ras/mapk pathway by affecting spry2 expression. 26159618_1 furthermore, foxq1 was identified as a direct target of mir-1271. 26159618_2 knockdown of foxq1 inhibited gc cell malignant behavior, whereas foxq1 overexpression partially restored the suppression effects of mir-1271. 26159618_3 additionally, mir-1271 expression was negatively correlated with foxq1 in gc tissues. 26159618_4 taken together, these results suggest that mir-1271 regulates foxq1 expression by directly targeting its 3'-utr. 26159618_6 this result further supported that mir-1271 targets foxq1. 21777146_1 in loss-of-function experiments, wild-type p53 mrna and protein expression was decreased by blocking hsa-mir-125a-5p. 21777146_2 to confirm whether the suppressed proliferation and enhanced apoptosis by hsa-mir-125a-5p are associated with p53, we detected the levels of p53 mrna and protein by qrt-pcr and western blotting, respectively. 21777146_3 p53 mrna and protein in a549 cells were significantly increased by either oligo-mir-125a-5p mimics or pgcsiu6-mir-125a-5p transfection . 23836929_1 a microrna, mir-129, that repressed kv1.1 mrna translation when mtorc1 was active. 23381389_1 we found upregulated mir-200a expression to increase e-cadherin and suppress the wnt/-beta-catenin pathway by targeting zeb1 and zeb2 in ga, thus delaying tumor growth in vivo. 26717041_1 uvrag was identified as a mir-183 target by microt-v4. 26717041_2 to confirm the bioinformatics-based predictions, we performed western blot analysis of uvrag expression in mir-183 or amo-183 transfected cell. 19063684_1 mir-196a target hoxc8 mrna in the 3'utr. 19063684_3 insertion of mir-196a targetsequences within hoxc8 3'utr leads to diminished luciferase reporter activity in the presence of mir-196a and increased activity in the presence of an mir-196a inhibitor. 24382668_1 forced expression of mir-224 suppressed pca cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating trib1. 26261515_1 we identified the smoothened gene as a functional target of mir-218, and found that smo overexpression counteracts the chemosensitizing effects of mir-218. 26261515_2 these findings suggest that mir-218 inhibits mdr of gastric cancer cells by down-regulating smo expression. 26261515_3 these results strongly suggest that mir-218 inhibits mdr in gastric cancer cells by down-regulating smo expression. 22958893_2 furthermore, rap1b was revealed to be directly regulated by mir-518b. 26713860_1 among the three potential targets, only zbtb7a mrna expression was suppressed by mir-125a in both cells. 26713860_2 suppression of zbtb7a protein expression by mir-125a was con铿乺med in a549 cells. 26713860_4 these results indicated that zbtb7a was a direct target for mir-125a. 26713860_5 expression of mir-125a and zbtb7a mrna showed a significant inverse correlation as calculated by spearman's correlation analysis. 21731696_1 in contrast to downregulation of the mir-34a targetgenes cmet and axl by overexpression of mir-34a in nsclc cell lines, the intrinsicexpression of cmet and axl was low in sclc cell lines and was not influenced byoverexpression of mir-34a. in summary, we demonstrated that ectopic expression of mir-34a could down-regulate mir-34a targetgenes in cells expressing the target. 21731696_2 we observed an inverse correlation between mir-34a and c-met but not bcl-2 expression in 5 sclc cell lines . 21731696_3 transfection of mir-34a precursor downregulated mrna expression of the axl gene in a549 and nci-h1299 nsclc cells by more than 70% , whereas the mrna expression of the axl gene in nci-h82 and nci-n592 sclc cells was too low to be detected by real-time pcr assay . 21731696_4 intriguingly, all the sclc cell lines tested in this study expressed low level of cmet and axl, two mir-34a targetgenes. 12737800_1 mutation experiments indicated that the hbl-1 3'utr is both necessary and sufficient to downregulate a reporter gene during development, and the let-7 and lin-4 micrornas are both required for hbl-1/gfp downregulation. 24633485_2 also, we discovered mir-429 plays a role in osteosarcoma by binding the 3'utr of zinc finger e-box-binding homeobox 1 mrna, and that overexpression of zeb1 could reverse the proliferation, subsequently blocking effect of mir-429. 23142051_1 in a direct test of endogenous targeting, individual mirna inhibition in metastatic lm2 cells led to an increased target-driven luciferase activity that was abrogated upon mutating the mirna target sites , revealing apoe to be directly targeted by mir-1908 and mir-199a-5p and dnaja4 to be directly targeted by all three mirnas . 23142051_2 these findings establish apoe and dnaja4 as direct targets of these mirnas in melanoma. 23142051_3 in agreement with this, we found a significant anti-correlation between the endogenous levels of both apoe and dnaja4 and the aggregate expression levels of the three mirnas across our collection of parental and metastatic lines . 22523078_1 the expression of mir-204/211 targetgenes was significantly increased only in cells co-transfected with both anti-mir-204 and -211. 26445551_1 itgb3 is a target of mir-98 and contributes to cell proliferation. 22593544_1 cotransfection experiments demonstrate that mir-146a's regulation of pressure-induced cytokine secretion depends on its targeting of both irak1 and traf6. 22593544_2 mir-146a target irak1 and traf6 in hsaepcs. in this study, we clearly demonstrate that overexpressing mir-146a down-regulates the irak1 and traf6 target in hsaepcs. 22593544_3 since this increase was not observed, these data indicate that mir-146a's ability to regulate pressure-induced cytokine secretion depends on its modulation of both the irak1 and traf6 target. 21339483_1 first, we demonstrated that overexpression of mir-100 represses mtor expression on both the mrna and protein levels in endothelial cells, whereas mir-100 inhibition resulted in a modest but significant upregulation of mtor . 21339483_2 confirming our findings, the binding site of mir-100 in the 3'-utr of mtor was characterized and experimentally verified by another group during the course of our study.10 21339483_3 next, we investigated the functional role of mtor in mir-100 signaling. 21339483_4 these data suggest that mir-100 regulates mtor expression not only in vitro but also in vivo . in summary, we demonstrate that mtor is a target of mir-100 in vascular cells and that it conveys its effect on cell proliferation. in addition, the stimulatory effect of antagomir therapy was abolished by simultaneous rapamycin treatment, demonstrating that the therapeutic effect of mir-100 inhibition in hind-limb ischemia is dependent on the intact signaling ability of its target gene mtor. 21339483_5 taken together, these results show that mir-100 inhibition enhances vascularization involving the upregulation of mtor in vivo. 26541455_1 moreover, the results showed that pre-mir-143 significantly reversed the upregulation of bag3 in shikonin treated gscs .furthermore, 26541455_2 our results identified that bag3 overexpression could markedly attenuate the enhanced cytotoxic effect on cell viability and induction of apoptosis by pre-mir-143 in shikonin treated gscs. 26541455_3 mir-143 enhanced the tumor suppressive effect of shikonin partly through the regulation of bag3 in gscs. 26541455_4 bag3 overexpression significantly abolished the enhanced apoptosis induced by pre-mir-143 in shikonin treated gscs. 23765281_1 we describe anovulation and infertility in female mice lacking the micrornas mir-200b and mir-429. 23765281_3 given that the zeb1 mrna level in the pituitary was not altered by deficiencies in these mirnas, the amount of zeb1 must be regulated by a posttranscriptional mechanism . 23765281_4 moreover, the increased level of zeb1 in mir-dko mice was decreased to near the wild-type level in the mir-200b and mir-429 transgenic mouse lines . 21363966_1 expression of ezh2, known to be negatively regulated by mir-214 , was about fourfold increased following injection of anti-mir-214 . in contrast, levels of actin and ezh2 in tooth germs treated with anti-mir-214 were significantly increased by 63 ± 5% and 71 ± 6%, respectively . 26323558_1 a luciferase reporter assay further confirmed that bcl-2 was a direct target of mir-873, and mir-873 decreased the level of the bcl-2 protein in cisplatin-resistant glioma cells. 26323558_3 therefore, mir-873 could downregulate the expression of bcl-2 by directly targeting the bcl-2 3'utr. 22733810_1 microrna-30d induces insulin transcription factor mafa and insulin production by targeting mitogen-activated protein 4 kinase 4 in pancreatic -beta-cells*. 22733810_3 together, our data conclusively demonstrated that map4k4 is a direct target of mir-30d in pancreatic -beta-cells. 22733810_4 further, a moderate reduction in map4k4 mrna was detected in pre-mir-30d transfected cells, indicating that the down-regulation of map4k4 by mir-30d was mediated via both translational repression and mrna instability. 22733810_5 this is likely due to the lower level of endogenous mir-30d in min6 cells, and anti-mir-30d only slightly reduced the mir-30d level, which had little effect on the map4k4-wt reporter activity. 22733810_7 the identification of map4k4 as one of mir-30d target describes an important role for mir-30d in protecting -beta-cell function against the inhibitory actions of tnf-alpha. 22034194_1 take together, these results suggest that mir-21 participates in cse/h s-mediated-smc differentiation by targeting sp1. 22034194_2 fig. 4. the sp1 3'-utr is a targetfor mir-21. 22034194_3 we further demonstrated that mir-21 repressed sp1 protein expression by directly targeting at sp1 3' untranslational regions, which in turn downregulated cse mrna expression and stimulated smc proliferation. 22034194_4 these mutations and sp1 abolished the suppressive effect of mir-21 precursor on the luciferase activity, verifying the functionality of the putative mir-21 binding sites in the human sp1 gene. 26499759_1 in addition, sirt1 was identified as a direct target of mir-22 by a luciferase reporter assay. 26499759_2 figure 4. mir-22 targets the 3'utr of sirt1 and downregulates its expression. 26499759_3 these results demonstrated that mir-22 negatively regulates sirt1 expression by directly binding to the 3'-utr of sirt1. 26499759_4 these findings suggested that mir-22 suppressed renal cancer tumorigenicity in vivo by targeting sirt1. 26634512_1 restoration of mir-577 down-regulates fgf-21 expression,the 3'-utr of the fgf21 gene contains binding sites for mir-577. 26634512_2 mir-577 suppresses the expression of a luciferase reporter gene harboring the 3'-utr of fgf21. 26634512_3 mir-577 inhibits fgf-21-activated fgf receptor downstream signaling cascades in -beta-cells. 26756701_2 4b suggesting that the mir- 4295 directly targeted runx3- 3'-utr. 20501832_1 these experiments validated the regulatory potential of mir-520h via binding within the pp2a/c 3'-utr and confirmed mir-520h-搈ediated modulation of endogenous pp2a/c in cancer cells. 20501832_2 together, our results indicated that pp2a/c is one target of mir-520h, and loss of pp2a/c promotes cancer cell mobility and invasive activity. 20501832_3 in this study, we identified pp2a/c as a target of mir-520h, which inhibited pp2a/c protein translation by binding to pp2a/c 3'-utr, and we suggest that e1a induces pp2a/c expression through a mirna regulatory mechanism. 26316103_1 mir-130b-3p negatively regulated erbb2ip expression by directly targeting the 3'-utr of erbb2ip. 26316103_2 the most interesting finding of the present study is that erbb2ip were demonstrated as apotential target of mir-130b-3p. 26316103_3 our findings of mir-130b-3p directly targeted erbb2ip and caused the following pathogenesis such as emt. 23353819_1 in addition, the patients whose tumours express high levels of mir-155/low levels of vhl exhibit even worse prognosis . 23353819_2 these findings suggest that mir-155 regulates vhl resulting in a more aggressive phenotype in breast cancer. 23353819_3 luciferase assays revealed that mir-155 repressed the activity of pmir-report-vhl-3'utr-0.8 but not pmireport-vhl-3'utr-0.68 . 23353819_4 these data indicate that the vhl is a direct target gene of mir-155. 23353819_5 these data suggest mir-155 down-regulation of vhl in vitro and in vivo. 18474618_1 in support of this hypothesis, expression of mir-126 alone in mll-enl-immortalized bone marrow cells decreased endogenous hoxa9 protein, while inhibition of endogenous mir-126 increased expression of hoxa9 in f9 cells. 18474618_2 mir-126, mir-145, and let-7 targetthe full-length hoxa9 cdna. 23135265_1 we further demonstrated that vimentin is a target of mir-378, and ectopic transfection of vimentin inhibited sox2 expression, resulting in decreased cell survival. 23135265_2 computational analysis indicated that mir-378 potentially target vimentin. 23135265_4 re-expression of vimentin was sufficient to cause cell death, suggesting that the effect of mir-378 on enhanced survival was at least partly taking place through repression of vimentin expression. 23135265_5 figure 8. confirmation of mir-378 targeting vimentin. 23637992_1 mir-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27 kip1. 23637992_2 we show that mir-221 is an oncogene and modulates cell proliferation and tumor progression via targeting p27 kip1 and emt transition in tnbcs both in vitro as well as in vivo. 23637992_3 knockdown of mir-221 in mda-mb-231, bt-20, and mda-mb-468 tnbc cell lines induced significant increases of p27 kip1 both in mrna expression and protein levels as shown in figure 2c and figure 2d, confirming that p27 kip1 is a target of this mirna in tnbcs. 24166503_1 an immunocytochemical study of hnrnp a1 and lc3-ii and the inhibition of autophagy by 3-methyladenine and atg7, p62 and bag3 sirna showed that mir-18a and hnrnp a1 formed a complex that was degraded through the autophagolysosomal pathway. 24166503_2 this is the first report showing a novel function of a mir in the autophagolysosomal degradation of an oncogenic protein resulting from the creation of a complex consisting of the mir and a rna-binding protein, which suppressed cancer progression. 25854542_1 mir-494 targets pten in tubular epithelial cells. 25854542_2 together, these data indicate that mir-494 targets pten and negatively regulates its expression. 22407237_1 in the cox multivariate analysis, it was shown that mir-107 expression in gastric cancer tissues was an independent prognostic factor for os and dfs. 22407237_2 significant inverse correlations were demonstrated between mir-107 and dicer1 mrna. 22407237_3 furthermore, the relationship between mir-107 and the mrna levels of its targetgene dicer1 was examined. 22407237_4 these results suggest that the expression of dicer1 mrna may be negatively regulated by mir-107. in the present study, we examined the relationship between mir-107 and dicer1 mrna levels, and demonstrated a significant inverse correlation. 26152337_1 additionally, one target of mir-1268a was show to be the adamts4 mrna and rs28599926 polymorphism might modify adamts4 expression. 26152337_2 to investigate whether the effects of mir-1268a rs28599926 polymorphism affected the expression of this gene, western blotting analysis was accomplished and proved that mir-1268a-wt can down-regulate adamts4 expression. 26152337_3 however, mir- 1268a-mt has no effects on the adamts4 expression . 21673106_1 of the mirnas identified to target klf4, only mir-143 and mir-145 were induced at least 1.5-fold by both bmp4 and tgf--beta, suggesting that they may be critical for bmp4- and tgf--beta-mediated reduction of klf4. 21673106_2 importantly, a decrease in klf4 mrna was observed concomitant with mir-143 and mir-145 up-regulation with bmp4/ tgf--beta stimulation. 21673106_3 under this condition, mir-143 mimic and mir-145 mimic reduced klf4 mrna to -68 and -48% of the endogenous level, respectively , suggesting that mir-145 is a more potent regulator of klf4 in comparison with mir-143. 21673106_5 to further confirm the direct association of mir-145 with the 3- utr of klf4, the predicted the mir-145 binding site in the human klf4 3- utr was cloned into a luciferase reporter vector. 21673106_6 overexpression of mir-145, but not a control mirna mimic, repressed expression of the wt klf4 binding site reporter . 21673106_7 importantly, mir-145 did not repress a vector containing a mutated mir-145 binding site . 21673106_8 these results demonstrate that the level of klf4 expression is negatively regulated by mir-145/143 in pasmc and plays a critical role in contractile gene expression levels. 23757351_1 direct binding of mir-223 to the 3'-utr of parp1 was further confirmed by a firefly luciferase assay. 23757351_2 parp1 was down-regulated at both the transcript and protein level upon mir-223 over-expression in eac cells, and we confirmed the direct binding of mir-223 to the 3'-utr of parp1 using a luciferase assay. 23757351_3 mir-223 over-expressing cells exhibited an aggressive phenotype; however, they were also more sensitive to dna-damaging agents due to the direct interaction between mir-223 and parp1. 23757351_4 high endogenous levels of mir-223 in eacs were significantly associated with lower parp1 levels, and those patients might benefit more from treatment with dna-damaging agents. 19270061_2 to understand posttranscriptional regulation of abcg2 and role of micrornas in drug disposition, we found that microrna-328 might readily target the 3'-untranslated region of abcg2 when considering target-site accessibility. 19270061_3 we then noted an inverse relation between the levels of mir-328 and abcg2 in mcf-7 and mcf-7/mx100 breast cancer cells, and the fact that mir-328 levels could be rescued in mcf-7/mx100 cells transfected with mir-328 plasmid. 19270061_4 luciferase reporter assays showed that abcg2 3'-utr-luciferase activity was decreased over 50% in mcf-7/mx100 cells after transfected with mir-328 plasmid, the activity was increased over 100% in mcf-7 cells transfected with a mir-328 antagomir, and disruption of mir-328 response element within abcg2 3'-utr led to a 3-fold increase in luciferase activity. 19270061_5 furthermore, the level of abcg2 protein was down-regulated when mir-328 was over-expressed, and the level was up-regulated when mir-328 was inhibited by selective antagomir. 19270061_7 lastly, mir-328-directed down-regulation of abcg2 expression in mcf-7/mx100 cells resulted in an increased mitoxantrone sensitivity, as manifested by a significantly lower ic50 value when compared to the control . 19270061_8 together, these findings suggest that mir-328 targets abcg2 3'-utr and consequently, controls abcg2 protein expression and influences drug disposition in human breast cancer cells. 26888602_1 altered microrna-122 and hif-1alpha expression in liver confirms hcc in mice. 26888602_2 altered liver microrna-122 and hif-1alpha correlates with hcc in mice. 26888602_3 n livers with tumors, loss of mir-122 expression with a significant up-regulation of mir-122 target hif-1alpha is seen. 23696548_1 microrna-124-mediated regulation of inhibitory member of apoptosis-stimulating protein of p53 family in experimental stroke.infusion of mir-124 decreased brain levels of iaspp, whereas inhibition of mir-124 enhanced iaspp levels and significantly reduced infarction in mouse focal cerebral ischemia. 19258506_1 ezh2 is a direct target of mir-101. 19258506_2 we conclude that mir-101 may be a potent tumor suppressor by altering global chromatin structure through repression of ezh2. to make a clear comparison, we plotted mir-101 rt-qpcr data from 20 individual patient samples from fig. 1b above the mrna levels of ezh2 that were obtained by rt-qpcr . 19258506_3 our results showed that ezh2 was up-regulated in the tumor samples relative to the adjacent normal specimens, whereas mir-101 is down-regulated in these same samples . 19258506_4 therefore, mir-101 represses ezh2 by binding to the 3'-utr of ezh2 in a direct and sequence specific manner. 23074286_1 we showed that proto-oncogene src kinase and akt are direct target of mir-23b. 23074286_4 these results indicate that src kinase is a direct target of mir-23b in pca. 23074286_5 we demonstrated that mir-23b inhibits src kinase at protein levels by directly binding to its 3'-utr complimentary sequences. 26492332_2 the rensp luciferase level measured by luminometer showed that mir-26a mimics bind with hmga2 in a dose-dependent manner ; further suggesting that hmga2 is a target of mir-26a. in the present study, we found that hmga2 is negatively regulated by mir-26a at the posttranscriptional level through a specific target site within the 3'-utr. 25955685_1 we reasoned that mir-206 could downregulate mrtf-a expression by targeting its 3'-utr in thyroid cancer and that mrtf-a was overexpressed in thyroid cancer, due to lack of mir-206. 25955685_2 all the data illustrated that mir-206 degraded mrtfa by targeting the specific sites predicted in silico in anaplastic thyroid cancer cells. 25955685_3 thus, we concluded that mir-206 inhibited migration and invasion via degrading mrtf-a expression. 26055330_1 mir-224 directly binds to the 3- utrs of slc4a4 and cftr mrnas. 17581274_2 mir-127 is located on chromosome 14q32, a region that is involved in several types of translocations in hematological malignancies and deleted by loh in solid tumors. 18199536_1 significantly, mir-214 induces cell survival and cisplatin resistance through targeting the 3'-untranslated region of the pten, which leads to down-regulation of pten protein and activation of akt pathway. 18199536_5 immunoblotting and rt-pcr analyses revealed that pten protein but not mrna was considerably decreased in mir-214-ransfected hiose-80 cells . in contrast, knockdown of mir-214 by 2'-o-me mir-214 in a2780cp cells, which express high levels of endogenous mir-214 , increased the protein level of pten . 18199536_6 further, the phosphorylation levels of akt, a major target of pten , and akt substrates glycogen synthase kinase 3' and p70s6k were elevated by ectopic expression of mir-214 and decreased by knockdown of mir-214 , suggesting that mir-214 target the pten/akt pathway. 18199536_7 inverse correlation of expression of pten and mir-214 was investigated in primary ovarian tumor specimens. of the 30 primary ovarian tumors examined, 13 exhibited down-regulation of pten and 17 had overexpression of mir-214 . 18199536_8 among 17 tumors with elevated mir-214, 11 had decreased pten levels . 18199536_9 these data further support the findings that the pten is a direct target of mir-214. 22890560_1 finally, luciferase activity assay showed that mir-92a inhibits klf4 expression by targeting its 3' -utr . 22890560_2 using gain and loss of function experiments, we showed that mir-92a modulates regulation of klf4 and mkk4 expression level in endothelial cells. 22890560_3 the results of this study reveal that mir-92a controls klf4 and mkk4 mrna and protein levels in endothelial cell. 22890560_4 furthermore, luciferase assays with wt and mutated 3' utr-binding sites confirmed that klf4 is a target of mir-92a. 21903586_1 remarkably, we found that the core binding factor cbf-beta had the most reduced activity, and the predicted binding sites are conserved among species , suggesting that cbf-beta is likely to be the most important targetregulated by mir-125b. 21903586_2 altogether, these data demonstrate that cbf-beta may be the target of mir-125b and that the putative binding sites are critical for mir-125b-mediated regulation of cbf-beta expression. 21903586_3 these data indicate that cbf-beta is an important functional target of mir-125b in malignant myeloid cells. 21903586_4 taken together, these results demonstrated that down-regulated cbf-beta by mir-125b is associated with the hematopoietic malignancies. 18539114_2 we observed a dramatic reduction in myb protein level upon ectopic expression of mir-150 . 18539114_3 next, we cloned the myb 3'utr into a luciferase reporter and found that mir-150 repressed reporter activity by more than 6-fold, again consistent with mir-150 targeting myb. 18539114_4 importantly, mutation of the four candidate mir-150 binding sites abrogated mir-150 repression, and a mutant mir-150 construct designed to be complementary to the mutant myb 3'utr binding sites restored mir-150-mediated repression, but did not affect the wild-type myb 3'utr . 18539114_5 these experiments establish that mir-150 negatively regulates the protein level of myb directly through its 3'utr. 25550988_1 together, these data suggested that mir-155 directly regulates socs1 expression. 25550988_2 collectively, these results suggest that mir-155 regulates dc maturation at least in part by targeting socs1. 26709677_1 the interaction between mir-363-3p and notch1 was confirmed by dual luciferase assays. 26709677_2 notch1 is the targeted gene of mir-363-3p. in the present study, notch1 is the targeted gene of mir-363-3p. 26265437_3 6b, overexpressing mir-1908 significantly suppressed pten levels in glioblastoma cells meanwhile silencing mir-1908 increased pten expression . 23447020_1 as we expected, the expression levels of target genes of mir-222, cdkn1b and cdkn1c, were downregulated in the nickel-induced tumor. 23447020_2 we conclude that mir-222 may promote cell proliferation infinitely during nickel-induced tumorigenesis in part by regulating the expression of its target genes cdkn1b and cdkn1c. 23447020_3 our results indicated that cdkn1b and cdknic, as the bona fide target genes of mir-222, may have a high correlation with the nickel-induce tumorigenesis. 23447020_4 these results indicated that mir-222 and its target genes, cdkn1b and cdkn1c, may play a role in the progress of the nickel-induced tumorigenesis. 17416635_1 by western blot analysis, down-regulations of caspase 3 were observed in cudr transfectants. 17416635_4 results support an idea that the protective effect of cudr on doxorubicin-induced apoptosis in a431 cells may be related to its effect on the down-regulation of caspase 3 rather than on the process of drug-induced caspase 3 activation. 19126550_1 as a control, we also monitored the levels of the previously reported let-7 target ras, using an antibody that recognizes both n-ras and k-ras and an antibody to n-ras . 19126550_2 under both the asynchronous and the synchronous protocols, pre-let-7b transfection led to a larger and more rapid decrease in cdc34 levels than in ras protein levels. 22411914_1 we thus concluded at this stage that mir-199b-5p bind the 3'-utr of cd15 mrna, thus impairing its expression. 22411914_2 this provided additional evidence that mir-199b-5p target cd15 in mb. of interest, we found that cd15 is an additional direct target of mir-199b-5p. 22999387_1 we also found that eag1 was widely over-expressed and inversely correlated with mir-296-3p in clinical specimens. 22999387_2 taken together, our findings suggest that mir-296-3p may play a role of mdr inglioblastoma at least in part by targeting eag1. 22999387_4 taken together, all these results strongly suggested that eag1 is a direct target of mir-296-3p in gbm cells. 22999387_5 mir-296-3p decreases cell growth and drug resistance by repression of eag1. 25405387_1 we identified zeb1 and crkl as potential targets of mir-429 by analyzing combined results from in silico search and global expression array of the same rna samples. 25405387_3 moreover, immunoblot assay showed that mir-429 reduced zeb1 and crkl significantly, which is a classical emt inducer in breast cancer . 23740614_1 these results indicated that upregulation of mir-335 can simultaneously suppress the invasiveness and promote apoptosis of lung cancer cell a549 and h1299 by targeting bcl-w and sp1. 26144250_2 confirming that ccnd3 was a direct target of mir-15b, overexpression of synthetic mir-15b significantly inhibited ccnd3 mrna and protein expression levels in l929 cells. 26144250_3 downregulated mir-15b and upregulated ccnd3 are confirmed in the b cells of an imiquimod-induced lupus-like model. 20057369_1 to determine whether the mir-519d bindsg sites on the ppara mrna are functional, we cotransfected a plasmid that expresses the renilla luciferase gene under the control of the cytomegalovirus promoter with the 3- utr region of the ppara mrna that contains the putative mir-519d bindsg sites and pre-mir-519d. 20057369_2 these data are compatible with a functional interaction between mir-519d and the 3- utr of the ppara mrna, thereby suggesting that changes in mir-519d levels may modulate the expression of genes regulated by this transcription factor. 26025408_1 more importantly, we provide evidence that igf1r is a direct and functional target of mir-30a. 26244545_1 we found that slc7a5 had the highest fold changes in both cell lines upon mir-126-3p overexpression, and adam9 had the second highest fold change in ftc-133 cells, which were used for both in vitro and in vivo assays in the present study. 26244545_2 both adam9 and slc7a5 play important roles in several cancers and have been shown to be targeted by mir-126-3p. 26244545_3 we found that mir-126-3p overexpression reduced slc7a5 protein expression in tpc-1 and xtc-1 cells and reduced adam9 protein expression in all three cell lines . 26244545_4 we also found that mir-126-3p overexpression downregulated adam9 protein expression in ftc-133-luc2 tumor xenografts that had been inoculated subcutaneously into the flanks of athymic nude mice and allowed to develop for 10 days. 26244545_5 we found that mir-126-3p overexpression significantly decreased luciferase activity as compared to the negative control , suggesting that mir-126-3p directly targets the 3'-utr region of adam9 and slc7a5 in thyroid cancer cells. 26244545_6 we next analyzed whether there was an association between mir-126-3p expression and adam9 and slc7a5 mrna expression in the tcga papillary thyroid cancer dataset, and found a significant inverse association with slc7a5 mrna expression but not with adam9 mrna expression. 26316085_1 mir-452 could binding the 3'utr of bmi1 and regulate its expression level. 26316085_2 the bioinformatics method was used to predict target gene of mir-452,suggeseted that 3'utr of bmi1 binds to mir-452. the result showed that mir-452 had a negative regulatory effect on bmi1 expression in both a549 and spca1 cell lines. 26316085_3 these data agreed with our previous hypothesis that bmi1 was one of the target genes of mir-452,and it could regulate bmi1 expression by binding its 3'utr in nsclc cell lines. 24297308_1 we found that restoration of mir-205 down-regulated the proliferative markers of dihydrofolate reductase and proliferating cell nuclear antigen and apoptotic regulator of bcl-2. 26251599_1 these results suggest posttranscriptional regulation of pten, p27kip1, and timp3 by anti-mir-221. 25997960_1 plc-beta1 was one of the potential targets of mir-205 and the dual luciferase report system demonstrated that plc-beta1 was a direct target of mir-205 in cells. 25997960_2 this indicates that plc-beta1 may be one of the direct targets of mir-205 in hcc tumors. 25997960_3 these data suggest that the over-expression of plc-beta1 is associated with a loss of mir-205 in hcc. 25997960_4 these results indicate that mir-205 promotes stemness of hcc by targeting plc-beta1 and increasing cd24 expression. 20831814_1 furthermore, we showed that mir-21 levels were increased in pdcd4-negative tumors, and that pdcd4 expression may be down-regulated in oscc by direct binding of mir-21 to the 3'utr pdcd4 mrna. 20831814_3 these results indicate that mir-21 directly binds the pdcd4 3'utr in oral carcinoma cells. 21527937_1 mir-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via zeb1 inhibition. 20682640_1 transfection of mir-1 resulted in a downregulation of timp3 mrna by 46%, whereas transfection of mir-206 downregulated timp3 mrna by 78%. 20682640_2 co-transfection of the two micrornas did not alter timp3 mrna downregulation to levels seen with mir-206 alone . 20682640_3 these data indicate that mir-206 is highly efficient in mediating timp3 downregulation, and that the less-efficient mir-1 does not compete with mir-206 in the regulation of timp3 gene expression. 20682640_4 therefore, downregulation of timp3 is primarily mediated by mir-206 similarly to connexin43 . 17943132_1 in addition, we demonstrate that ifnbeta treatment leads to a significant reduction in the expression of the liver-specific mir-122, an mirna that has been previously shown to be essential for hcv replication. 21636706_1 either downregulation of mir-21 or overexpression of its target, pdcd4, in glioblastoma-derived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar. 21868760_1 gab2 and fn1 are targeted by let-7g to regulate mammary carcinoma cell migration and invasion. 21868760_3 consistently, forced expression of let-7g diminished gab2 expression at both mrna and protein levels , indicating gab2 is a bona fide target of let-7g. 21868760_4 similarly, we identified fn1 as a direct target of let-7g and mapped the major let-7g binding site within the fn1 3'-utr . 21868760_5 we showed that sirna-mediated depletion of fn1 expression significantly abrogated the enhanced migration and invasion consequent to let-7g depletion . 21868760_6 thus, both gab2 and fn1 play important roles downstream of let-7g. 22189055_1 mir-610 directly target the 3'-utr of vasp and represses its expression. 22189055_2 these data demonstrate that mir-610 is downregulated in human gastric cancer tissues and there is an inverse correlation between vasp and mir-610 expression levels in cultured gastric cancer cells after egf stimulation. . 22189055_3 taken together, these data provide strong evidence that mir-610 specifically target vasp and represses its expression in gastric cancer cells. 22189055_4 these results indicate that mir-610 inhibits gastric cancer cell migration and invasion in vitro by repressing vasp expression. 26316586_2 foxo1 overexpression vector lacked 3'-utr together with mir-370 mimic transfection strongly abrogated mir-370-induced cell proliferation and the formation of capillary-like structures in huvecs. 26316586_3 taken together, our results revealed that the upregulation of mir-370 might facilitate the repair of amputated fingers by regulating angiogenesis through targeting foxo1. 26316586_4 these results demonstrated that foxo1 was a bona fide target of mir-370. 25703026_1 the results presented that antagonism of mir-100 increased the expression level of hs3st2, the target gene of mir-100, and further resulted in the activation of the notch-apoptosis pathway in tumor cells. 26744318_1 a significant inverse correlation was found between mir-100 and mtor in invasive breast cancers ,5a, implicating mtor as a target of mir-100 in breast cancer. 26194864_1 since our data suggest a relationship between mir-203 and slug in gc cells, we checked whether mir-203 may target slug mrna. 26194864_2 our data show that the mir-203 binding sites in the slug mrna sequence 3'-utr ranged from 351th base site to 358th base site. 25797263_1 lrp6, trim29 and pygo2 are direct targets of mir-432. 25797263_2 suppression of lrp6, trim29, and pygo2 is functionally important for the biological effects of mir-432 in hcc. 21558425_1 accordingly, dj1 and parkin expression was reduced in pd brain samples displaying strong mir-34b/c downregulation. 21558425_2 our data suggest that parkin and dj-1 are indirect target of mir-34b/c. 21558425_3 these findings suggest that mitochondrial dysfunction linked to mir-34b/c downregulation may involve, at least in part, a decreased expression of dj1 and parkin. 26846737_1 our results demonstrated the novel mechanism controlling pten expression via mir-301a in es cells. 26846737_2 although mir-301a might influence the expression of many genes, we focused on pten mrna as a mir-301a target in es cells. 26846737_3 furthermore, sequence analysis suggested possible association of mir-301a with the 3'-utr of pten mrna. 22922827_1 the upregulation of mir-15a and mir-16-1 in the cell line sosp-9607 induces apoptosis and cell cycle arrest. 25661343_1 bancr regulated lc proliferation and migration via p38 mapk and jnk inactivations. 25661343_2 when bancr was up-regulated, p38 mapk and jnk pathways were both inactivated. 25661343_3 more importantly, when p38 mapk and jnk were inactivated by the inhibitors, inhibition of bancr expression remedied the inactivation 23516428_1 dnmt3a is a mir-29c target in silico analysis showed high score and a low mean free energy for dnmt3a and mir-29c interaction indicating that dnmt3a is a robust target of mir-29c. 23516428_2 we confirmed the mir-targetrelationship experimentally using dnmt3a 3'-utr luciferase vector assays by challenging with premir-29c. 23516428_3 the mir-29 seed sequence in the 3'-utr of dnmt3a mrna. 12808467_1 hes1 is a target of mir-23 in nt2 cells. 12808467_2 these results suggest that ts23 in hes1 mrna is a target of mir-23 and that the natural near complementarity of ts23 to mir-23 is necessary for mir-23- mediated post-transcriptional silencing of gene expression. 12808467_3 this observation suggests that the function of mir-23 has been conserved phylogenetically as a regulator of hes1 in human and mouse. 12808467_4 these results further suggest that synthetic mir-23 might suppress the expression of the gene for hes1 at the translational level. 22593189_1 mir-103/107 targetedapk and klf4 in crc cells. 22593189_2 overexpression of mir-103/107 reduced the activities of dapk and klf4-based reporters, whereas antagomir-103/107 markedly increased the activities of 2 reporters . 22593189_3 these results indicate that mir-103/107 suppress the expression of dapk and klf4 by targeting their 3'-utrs. 22593189_4 these data support that mir-103/107-dependent regulation of dapk and klf4 is associated with metastasis and poor prognosis of patients with crc. 18983236_1 the inhibition of mirna-221 and -222, which are abnormally expressed in melanoma and favor the induction of the malignant phenotype by downregulating c-kit receptor and p27kip, might in the future represent an efficient treatment for translation into the clinical setting. 20181935_1 we further show that ccl8/mcp-2 is a target for mir-146a in hiv-1 infected microglia, as overexpression of mir-146a prevented hiv-induced secretion of mcp-2 chemokine. 21616184_4 additional validations include exogenous reporters have been mutated to disrupt targeting by a ectopic mirna, ectopic mirna suppresses endogenous target mrna and/or protein levels, de novo infection with kshv represses endogenous target expression, mirna inhibitors and/or mutant virus display derepression of endogenous target mrna and/or protein levels, and repression of mirna target is observed in kshv clinical samples. 21672940_1 further studies showed that mir-124 could directly targetthe 3'-untranslated region of both rock2 and ezh2 mrnas, and suppress their mrna and protein expressions. 21672940_2 conversely, when we performed luciferase assays using a plasmid harbouring the 3'-utr of rock2 and ezh2 mrnas, in which the binding sites for mir-124 were inactivated by site-directed mutant genesis, the luciferase activity of mutant reporters were unaffected by the simultaneous infection of mir-124 . 21672940_3 meanwhile, the protein levels of rock2 and ezh2 were also substantially decreased after ectopic overexpression of mir-124 in lm9 and hepg2 cell lines as evidenced by western blot assays . 21672940_4 collectively, these data support the bioinformatics predictions indicating rock2 and ezh2 3'-utrs as direct target of mir-124. 21672940_5 taken together, these results provide evidence suggesting that rock2 and ezh2 are involved in mir-124-regulated hcc cell invasiveness and metastasis. 26332146_2 further-more, we found that overexpression of mir-372suppressed igf2bp1 protein level in the cells. 26332146_3 our dataobtained from gain-of-function approaches conmmed that igf2bp1 is a direct target gene of mir-372. 26332146_4 mir-372 overexpressing 786-o cells waspartially increased after igf2bp1 transfec-tion. 17715156_1 mir-1 and mir-133 are involved in regulating cell fate with increased mir-1 and/or decreased mir-133levels favoring apoptosis and decreased mir-1 and/or mir-133 levels favoring survival. 17715156_2 post-transcriptional repression of hsp60 and hsp70 by mir-1 and of caspase-9 by mir-133 contributes significantly to their opposing actions. 21534877_1 mirna-15a transfected myeloma cells were arrested in g1/s checkpoint and secreted less vegf compared to control transfected cells, although no significant difference was found in vegf mrna levels. 26206152_1 hdac4 is a target of mir-10b. 26206152_2 ectopic expression of mir-10b resulted in the down-regulation of hdac4 in mcf-7 cells and, conversely, down-regulation of mir-10b in mcf7tr cells resulted in increased expression of hdac4 . 26626440_1 the dual-luciferase reporter assay verified that that mir-186 combined with the 3- -untranslated region of abcb1. 26626440_2 our results demonstrate that mir-186 significantly decreased the relative luciferase activity of the wild-type abcc1 3'-utr compared with the mutant abcc1 3'-utr, indicating that mir-186 may directly bind to the 3'-utr of abcc1 . 26626440_3 therefore, we suggest that mir-186 may increase cell sensitivity of ovarian cancer cells lines to paclitaxel and cisplatin by targeting abcb1 but not abcc1. 26626440_4 based on these findings and our study results, we consider that mir-186 may inhibit the development of drug resistance by targeting abcb1 and regulating gst-蟺 expression in ovarian cancer cells. 21642990_2 briefly, mir-19b regulates pten expression15 . 21642990_3 mir-20a and mir-26a reduce levels of pten and phf6, and mir-20a has similar effects on bim. 21642990_4 ikzf1, nf1 and fbxw7 are regulated by mir-27a, and mir-148a regulates ikzf1, pten and bim. 21642990_5 similarly, mir-92 affects ikzf1, fbxw7 and, to a lesser extent, bim and pten, but not mouse nf1. 21642990_6 mir-223 is a strong regulator of fbxw7. 21642990_9 mcl1 is a target of the fbxw7 e3 ligase28,29 and accordingly, we found that mcl1 levels are increased in mouse leukemias expressing mir-223 and mir-92, both of which target fbxw7 . 21642990_10 there are cell-line-搒pecific differences, and in koptk1 cells, which express high levels of mir-148, an antagomir against mir-148 restores bim and pten expression . 21642990_11 this indicates that mir-148 maintains bim and pten repression in koptk1 cells but not in tall-1 cells. 21642990_12 similarly, co-expression of mir19b and mir-92 or mir-19b, mir-26a and mir-92 produced additive effects on the bim and pten 3'-utr reporter activity, respectively . 19347736_1 it has previously been shown that mir-34a is directly regulated by p53 and target bcl-2. 19347736_2 moreover, bcl-2 is downregulated by mir-34 in cell lines , which might be in line with their possible role in cll pathogenesis. 26693396_1 thus, forkhead box f2 was identified as a downstream target of mir-519a in hcc. in conclusion, mir-519a is a novel prognostic predictor for hcc patients and it may potentiate proliferation and inhibits apoptosis of hcc cells by targeting foxf2. 26693396_3 taken together, these results indicate that foxf2 is a direct downstream target of mir-519a in hcc. 21551130_1 in the present study, we found that overexpression of mir-29c inhibited cyclin e expression by targeting 3' untranslated region of cyclin e messenger rna in escc cells. 21551130_2 these results indicated that mir-29c target cyclin e mrna at 3- utr and impairs cyclin e mrna translation. 21551130_3 these results provided further evidence to demonstrate that overexpression of mir-29c regulate cyclin e expression in escc cells. 21551130_4 these results suggested that in escc cells, mir-29c have the potential of regulating g1 to s cell cycle progression, and cyclin e play a key role in this effect. 19682266_1 the authers reported that the conserved micm rna downregulates ybfmn expression through complementary interaction with the translational initiation region of ybfm messages, causing them to be degraded.hfq 19682266_2 binds efficiently to micm and ybfm mrna and is essential for in vivo stability of the srna as well as for micm-mediated decay of the ybfmn messages in vitro. 26535690_1 mir-29a is a potential mirna directly targeting stat3. 26535690_2 it was verified that stat3 was a new target gene of mir-29a. 26535690_3 these data indicate that stat3 is a direct target gene of mir-29a. in summary, we examined the role of mir-29a in sepsis. 26535690_4 stat3 was predicted as the target gene of mir-29a by targetscan and verified the predicted result. 21283761_2 we found that mir-k12-7 targeted the rta 3' untranslated region in a seed sequence-dependent manner. 26770408_1 we validated that adamts13 is a target for mir-525-5p with a luciferase reporter activity assay. 26770408_2 furthermore, mir-525-5p was identified and characterized to interact with 3'-utr of adamts13; thereby, mir-525-5p antagomir was capable of upregulating adamts13 expression that might protect neurons from ischemia-induced cell death. 26770408_3 collectively, these data indicate that adamts13 is a potential target of mir-525-5p. 26770408_4 this is consistent with the idea that an ischemia-induced reduction in mir-525-5p negatively regulates adamts13 expression. 23166305_1 mir-145 negatively regulates the expressionand function of p-gp through the repression of mrna by direct interaction on the 3'-utr of mdr1 mrna. in the present study, we focused on the decreased mir-145 in the small intestine after liver i/r because the 3'-utr of mdr1 as well as mdr1a mrna have a potential mir-145 target site as predicted by in silico analysis . the results from the luciferase assays using mdr1 3'-utr reporter plasmid in hek293 cells and the downregulation of mir-145 in caco-2 cells demonstrated that mir-145 negatively regulates the expression and function of p-gp through the repression of mrna by direct action on the 3'-utr of mdr1 mrna . 23166305_2 therefore, it is strongly suggested that mir-145 regulates the expression and function of p-gp through the translational repression of mdr1 mrna. 20444872_1 after showing that hoxa9 up-regulated mir-155, and that mir-155 mediates at least some figure 2.mir-155 expression is highest in bm stem cell pools, mir-155 is downstream of hoxa9, and mir-155 down-regulates pu.1. 20444872_2 functionality, we used the available prediction programs to identify pu.1 as a putative target for mir-155 . 20444872_4 to test the effects of mir-155 on pu.1 expression, we generated a retroviral vector that expressed a mir-155 hairpin precursor. 20444872_5 although this vector produced an ~600-fold increase in mir-155 in 293t cells , mir-155 expression increased only 8-fold following viral infection of wild-type bm cells . 20444872_6 infection of either wild-type or hoxa9-deficient bm cells with this mir-155 expression vector resulted in an ~50% decrease in pu.1 protein , a finding that has been reported by others since the inception of this work . 20444872_7 these findings strongly suggested that hoxa9 might regulate pu.1 via mir-155, and that this might be a significant window into understanding how the hoxa9 protein influences hematopoiesis. 26303523_1 online software was used to identify smad7 mrna as a potential target of mir-195. 26303523_2 the direct interaction of mir-195 and smad7 mrna was investigated using a biotinylated mir-195 pull-down assay. 26303523_3 overexpression of a mir-195 precursor lowered cellular levels of smad7 protein; conversely, antagonism of mir-195 enhanced smad7 translation without disturbing smad7 mrna levels. 26303523_4 a luciferase reporter assay revealed a repressive effect of mir-195 via a single smad7 3'-utr target site, and point mutation of this site prevented mir-195-induced repression of smad7 translation. 20018894_2 luciferase activity was significantly decreased by the overexpression of mir-34a, but not by mir-24. 20018894_3 these results suggested that mir-24 and mir-34a down-regulate the hnf4alpha expression by different mechanisms, i.e. mrna degradation and translational repression, respectively. 20018894_4 these results support that mir-24 and mir-34a down-regulate the hnf4alpha expression through recognizing the elements in the coding region and the 3'-utr of hnf4alpha mrna, respectively. 20018894_5 this was accompanied by increases of the mature mir-24 and mir-34a levels . 20018894_7 it was considered that pma or h2o2 repressed the hnf4alpha expression though increasing the mir-24 and mir-34a levels. 25480586_1 taken together, these data suggest that mir-101 may inhibit proliferation of saos-2 cells by targeting mtor. 22407479_4 since the 3'-utr region from chip mrna is specifically targeted by mir-764-5p, we reason that the inhibition of the wt luciferase reporter is due to the expression of mir-764-5p during the osteoblast differentiation. 25123132_1 kd of mir-146a caused decreased proliferation and increased apoptosis, effectively ablating the effects of p53 loss. 25123132_2 furthermore, we found that mir-146a upregulation decreased nf-κb expression and downregulated the nf-κb-dependent extrinsic apoptotic pathway and antagomir-mediated mir-146a kd restored expression of these components, suggesting a plausible mechanism for mir-146a-dependent cellular responses. 22733138_1 moreover, mir-24 overexpression can overcome apoptosis resistance in cancer cells via downregulation of xiap expression, and the resulting cancer cell death induced by tumor necrosis factor-related apoptosis-inducing ligand is executed by the canonical caspase-mediated apoptosis pathway. 21453483_1 co-transfection of a mir-223 expression vector with pmir-artn led to the reduced activity of luciferase in a dual-luciferase reporter gene assay, suggesting that artn is a targetgene of mir-223. 21453483_2 consistent with this result, silencing of mir-223 using an mir-223 inhibitor resulted in an increase of artn protein level in ec9706 cells . 21453483_3 these results indicate that artn is post-transcriptionally regulated by mir-223. 21453483_4 figure 3 mir-223 interacts with the artn 3'utr and regulates endogenous artn protein expression. 21453483_5 furthermore, artn mrna was a direct and functional target of mir-223. 26884822_1 as a result of this, we demonstrated that mir-30a could target snail 1 by binding to its 3'-utr in myocardial fibroblasts. 26884822_2 results of dual-luciferase reporter assay also suggested that mir-30a could directly target snail 1gene. 26884822_3 our study found that mir-30a decreased significantly in cardiac fibrosis cells and tissues, while up-regulation of mir-30a could inhibit the cardiac fibrosis by targeting snail 1. 26885275_1 mlk3 is a direct target of mir-199a-5p in bladder cancerous cells and contributes to tumor-suppressing effect of mir-199-5p. 23402302_1 il-32 expression was induced by active hcmv infection and could be functionally down-regulated by ectopically expressed hcmv-mir-ul112-1. . 23925649_1 egfp reporter assay, real-time pcr and western blot were performed to verify that mir-223 targeted abcb1 3'utr directly, and mir-223 downregulated abcb1 at both mrna and protein levels. 20844036_2 from luciferase assays with reporter plasmids containing the 3' untranslated region of tweakr suggest a targeting of tweakr by mir-k10a.the 20844036_3 expression of tweakr was downregulated in cells transfected with mir-k10a as well as during de novo kshv infection. 24953694_1 overexpression of mir-29c with mir-29c mimic enhanced iav-induced a20 protein expression and conversely that mir-29c inhibitor significantly blocked iav-induced a20 protein expression in a549 cells. 26832151_1 mir-505 directly targets tgfa and regulates tgf-alpha expression in ec cells 25344561_2 we observed mir-15b directly targets tet3 and represses tet3 and 5hmc expression levels. 25344561_3 the mutation of the mir-15b target site within the tet3 3- utr abolished the inhibitory effects of mir-15b on luciferase expression ,4c, suggesting that tet3 is directly regulated by mir-15b. 25344561_4 taken together, these data demonstrate that mir-15b can directly target tet3, thereby regulating tet3 levels and 5hmc expression. 25755729_2 taken together, these results indicate that mir-21 negatively regulates wwp1 expression in epcs by directly targeting the 3'-utr of the wwp1 gene. 20676037_1 studies of the underlying mechanisms showed that the mrna encoding stathmin, a developmentally regulated cytosolic phosphoprotein with a catastrophe-promoting microtubule-depolymerization acitivty, is a direct target of mir-9 regulation. 20676037_2 thus, stathmin is a key essential target of mir-9. 20676037_4 this finding confirms the developmental function of mir-9 in an in vivo setting, in which stathmin seems to be a key target as well. 18790736_1 of the elevated mirnas in eralpha-negative cells, mir-221 and mir-222 directly interact with the 3'-untranslated region of eralpha. 18790736_2 mir-221 and mir-222 negatively regulate er and render cells resistant to tamoxifen. 18790736_3 era protein but not mrna is suppressed by mir-221 and mir-222. 18790736_4 the luciferase activities of pmir-er alpha1-3 'utr but not pmir-eralpha 2-3' utr were significantly suppressed in mir-221/222-positive mda-mb- 468 cells but not in mir-221/222- negative mcf-7 cells . 18790736_5 mir-221 and mir-222 play a significant role in the regulation of er expression at the protein level and could be potential target for restoring er expression and responding to antiestrogen therapy in a subset of breast cancers. 18790736_6 these findings further support the notion that eralpha is a direct target of mir-221 and mir-222 at the translation level. 26617792_1 furthermore, we demonstrate hmgb1 was a directly target of mir-142-3p in nsclc cells, and confirmed the target specificity between mir-142-3p and the hmgb1 3'-untranslated region by luciferase reporter assay. 26617792_2 furthermore, we identified the downstream target of mir-142-3p and find mir-142-3p was directly targeted hmgb1 in nsclc. 26617792_3 these results suggest that 3'-utr of hmgb1 is a direct target of mir-142-3p. in summary, we present here the first evidence that hmgb1 is potential target for mir-142-3p and that mir-142-3p may modulate nsclc cell tumorigenesis through targeting hmgb1. 20619534_1 taken together, our results suggest that mir-126 may function as a tumour suppressor in gastric cancer, with crk as a direct target taken together, these results indicate that 3' utr of crk carries the direct binding sites of mir-126. 20619534_3 5c, the crk protein level was decreased in mir-126 precursor-transfected sgc-7901 cells compared with control precursor-transfected sgc-7901 cells. 20619534_5 these results strongly suggest that mir-126 negatively regulates crk expression post-transcriptionally. 26867765_1 taken together, our data strongly suggests that by binding mir-485-5p, uca1 leads the derepression of mmp14, thereby imposing an additional mmp14 expression at posttranscriptional regulation level. 21266536_1 figure 3. lefty1 3'-utr is targeted by mir-302s. 21266536_2 together, this functional data support a direct interaction of mir-302s and lefty1 3'-utr. 21266536_3 we found that the nodal inhibitors lefty1 and lefty2 are post-transcriptionally targeted by mir-302s in hescs. 21266536_4 taken together, these results suggest that the mir-302-lefty axis sustains pluripotency marker expression and impairs germ layer specification in differentiating hescs. 21266536_5 overall, these findings suggest that lefty is negatively modulated by mir-302s in hescs, which play an important role in maintaining the balance between pluripotency and germ layer specification. 19330006_1 these results strongly suggest that mir-9 represses tlx expression through the predicted targetsite in tlx 3- utr. 19330006_2 marked reduction of tlx protein levels and mrna levels were detected in mir-9 transfected cells , indicating that mir-9 down-regulates tlx expression. 19330006_3 these results strongly suggest that mir-9 regulates neural stem cell proliferation and differentiation, at least in part, by inhibiting tlx expression through its 3- utr. 19330006_4 these results strongly suggest that mir-9 regulates neural stem cell differentiation through targeting tlx expression in vivo. 22049409_1 we identify common target molecules of mir-279 and pros in bioinformatics analysis, and show that overexpression of the transcription factors nerfin-1 and escargot issufficient to induce formation of co 2 neuronson maxillary palps. 22049409_2 our results suggest that prosperore stricts co 2 neuron formation indirectly via mir-279 and directly by repressing the shared target molecules, nerfin-1 and esg, during olfactory system development. 22049409_3 using rnai, loss of function analysis, and overexpression, we demonstrate that upregulation of two pros and mir-279 target genes, nerfin-1 and escargot,is necessary and sufficient for the formation and mistargeting of mp co 2 neurons. 20566875_1 fig. 2. the expression of human and mouse abca1, and of mouse abcg1 are regulated by mir-33. 20566875_2 cotransfection of a plasmid expressing mir-33 resulted in a 50- 60% decrease in luciferase activity when the reporter plasmid contained the human/mouse box 1 sequence from abca1 or the mouse abcg1 sequence . 20566875_3 the specificity of this effect is supported by the finding of no repression when the reporter gene contained either sequences corresponding to box 2 of abca1 , or mutant box 1 or mutant mouse abcg1 sequences . 20566875_4 collectively, these results identify human and murine abca1 and murine abcg1 as bona fide targets for mir-33. 20566875_5 collectively, these in vitro and in vivo studies strongly suggest that mir-33 modulates intracellular cholesterol homeostasis and lipoprotein metabolism, presumably by silencing the expression of abca1. 23653113_1 results suggested mir-424-5p was significantly upregulated in pancreatic cancer and suppress the expression of socs6, and mir-424-5p increased proliferation, migration and invasion of pancreatic cancer cells, while inhibited cell apoptosis. 26597919_1 c/ebpa and pparg were the target genes measured for mir-27a/b . 26604788_1 we found that protein expression level of mmp16 was down-regulated and upregulated by mir-132 mimics and mir-132 inhibitor transfection, respectively . 25691332_1 mir-30e induces egfr up-regulation by targeting cbl-b. 25691332_2 the expression of cbl-b mrna was also reduced by transfection with mir-30e. 25691332_3 the 3- utr of cbl-b is directly targeted by mir-30e. 25691332_4 to further confirm that mir-30e exerts its action on egfr-induced invasion mainly by targeting cbl-b. 22848417_1 mir-182 was shown to have activity on mrna expression by targeting the 3' untranslated region of mitf, bcl2 and cyclin d2. 22848417_2 mir-182 was shown to have activity on mrna expression by targeting the 3'utr of mitf, bcl2 and cyclin d2. 22848417_4 our results demonstrated that mir-182, a p53 dependent mirna, suppressed the expression of mitf, bcl2, cyclin d2 and functioned as a potent tumor suppressor in uveal melanoma cells. 24331995_1 overexpression of mir-424 decreased vascular endothelial growth factor and kdr protein levels, whereas mir-424 inhibition significantly elevated them. 24331995_3 these results indicated vegf and kdr are targets of mir-425 during endothelial differentiation of hdpcs. 18464261_1 tongue scc cell lines transfected with mir-133a and mir-133b precursors displayed reduction in proliferation rate. in addition, the number of apoptotic cells was increased in response to the introduction of precursors. 18464261_2 computational target gene prediction suggested that both mir-133a and mir-133b are targeting transcript of pyruvate kinase type m2 , a potential oncogene in solid cancers. in tongue scc cell lines, pkm2 expression was reduced in response to mir-133a and mir-133b precursors transfection. 18464261_3 our results suggested that aberrant reduction of mir-133a and mir-133b was associated with the dysregulation of pkm2 in scc of tongue. 23321675_3 we used mirna target prediction programs to identify mir-148a as a regulator of hpip. 23321675_4 expression of mir-148a in hepatoma cells reduced hpip expression, leading to repression of akt and erk and subsequent inhibition of mtor through the akt/erk/foxo4/atf5 pathway. 19372139_1 knockdown of mir-18a* by transfection with anti-mir-18a* inhibitor and also let-7a by let-7a inhibitor upregulated the ras expression in wrl-68 cells. 19372139_2 a431 cells had the relatively highest k-ras expression with the lowest mir-18a* level, followed by ht-29 cells and wrl-68 cells. 19372139_3 results from figures 2 and 3 therefore suggest that k-ras oncogene is a target of mir-18a*. 19372139_4 results from figure 4 therefore validate that k-ras oncogene is a target of mir-18a*. 17308079_1 mir-124a epigenetic silencing mediates cdk6 activation and rb phosphorylation. 17308079_3 overexpression of mir-124a induced a reduction of cdk6 protein level. 23533157_1 mechanistically, erk-dependent induction of mir-18a* directly represses expression of dll3, an autocrine inhibitor of notch, thus enhancing the level of activated notch-1. 23533157_2 these results demonstrate the ability of mir-18a* to negatively regulate dll3 protein expression, thus confirming mir-18a* activity. 23533157_3 taken together these results clearly demonstrate the ability of mir-18a* to directly modulate dll3 protein expression levels. 22958366_1 furthermore, mirna expression analysis showed that mir-130b, targeting the ppar--gamma 3'-untranslated region , and mir-374b, targeting the c/ebp--beta 3'-utr, were significantly increased in the lp group compared with the sp group; other candidate regulatory mirna were expressed similarly in both groups. 22958366_2 dual luciferase activity assay results indicated that mir-130b directly recognised and bound to the 3'-utr of ppar--gamma and thereby suppressed ppar--gamma gene expression. 22958366_3 similar results were found for mir-374b and the 3'-utr of c/ebp--beta. 25151966_1 mir-340 inhibits tumor cell proliferation and induces apoptosis by targeting multiple negative regulators of p27 in non-small cell lung cancer. 21960592_1 mir-16 targetchek1 showed increased expression in t -negative fls, whereas tcl1a expression was reduced, in line with a partial loss of the germinal center b-cellphenotype in this fl subset. 21960592_2 figure 4 differential expression of the mir-16 target chek1 between t -positive and t -regative fl without bcl2 expression as detected by immunohistochemistry. 22792280_1 up-regulation of mir-107 partly suppressed the epcs differentiation induced in hypoxia, while down-regulation of mir-107 promoted epc differentiation. 22792280_3 this study indicated that mir-107 was up-regulated in hypoxia to prevent epcs differentiation via its target hif-1-beta. 22792280_4 this is because lenti- hif-1-beta increased endogenous hif-1-beta expression, while lenti-mir107 reduced mir-107 direct target hif-1-beta expression in epcs. 22792280_5 down-regulation of cd31 and enos after up-regulation of mir-107 was offset by up-regulation of hif-1-beta , which showed the up-regulation of mir-107 would inhibit epcs differentiation via inhibiting hif-1-beta. 22792280_6 from these collective results we can conclude that mir-107 was up-regulated in hypoxic conditions to prevent epc differentiation via its target hif-1-beta. 26513157_1 the bdnf gene was identified as a direct target of mir-10b using a dual-luciferase reporter assay. 26513157_2 these results demonstrate that mir-10b downregulates bdnf expression in granulosa cells by directly targeting the 3 ' untranslated regions and plays an important role in inhibiting granulosa cell proliferation by targeting bdnf. in the present study, our results provided novel evidence that mir-10b suppresses cell proliferation through targeting bdnf in goat. 23907579_1 treatment of gastric cancer cells with dha increased mir-15b and mir-16 expression, caused a downregulation of bcl-2, resulting in apoptosis of gastric cancer cells. 23742934_1 microrna-7 downregulates xiap expression to suppress cell growth and promote apoptosis in cervical cancer cells. 23792642_1 we demonstrated that atg7 is a potential target for mir-17, and this mirna could negatively regulate atg7 expression, resulting in a modulation of the autophagic status in t98g glioblastoma cells. 22821565_1 in conclusion, our functional screening uncovers multiple mirnas that regulate the cellular responsiveness to tgf-b signalling and reveals important roles of mir-199a in gastric cancer by directly targeting smad4. 22821565_2 these data demonstrate that the predicted mir-199a-paired region is required for the regulation of smad4 by mir-199a. 22821565_4 in this study, we showed that overexpression of mir-199a conferred a growth advantage to gastric cancer cells, at least partially through promoting cell proliferation and protecting cells from tgf-b-induced apoptosis, suggesting that mir-199a may play an oncogenic role in gastric tumourigenesis via regulation of smad4. 26801246_1 this results supported that mir-508-3p might recognize the binding sites in nfkb1 3'utr and directly suppressed nfkb1 expression. 26801246_2 nfkb1 is a direct target of mir-508-3p in gc. 26801246_3 suggesting mir-508-3p inhibits the dna binding ability of nfkb1 by down-regulating nfkb1. 26739093_1 staphylococcal lipoteichoic acid activated tlr2 to induce mir-143 in keratinocytes, and mir-143, in turn, directly targeted 3 ' utr of tlr2 to decrease the stability of tlr2 mrna and then decreased tlr2 protein, thus inhibiting p. acnes-induced proinflammatory cytokines. 26739093_2 taken together, these results demonstrate that lta induces mir-143 directly targeting 3 ' utr of tlr2 and then specifically inhibits p. acnes-induced tlr2 production, thus inhibiting p. acnes-induced inflammatory response. 26739093_3 the mechanism for lta-mir-143-mediated suppression of tlr2 signaling is accomplished by mir-143 targeting 3 ' utr of tlr2 and then decreasing the produc- tion of tlr2 protein, an event we show has a major role in inhibiting p. acnes-induced cutaneous inflammation. 21451113_2 we found that mir196a-2, mir196b, and mir222 specifically repressed expression of reporters with the hox6 utr and the hoxa4 utr but did not affect expression of a hoxd13 utr reporter . 21451113_3 hoxb6 was also specifically repressed by mir196a-1 and mir221 in a seed-dependent manner and by mir31 and mir324 in a seed-independent manner. 23386720_1 mechanistic studies showed that mir-200s significantly repress the expression of zinc finger e-box binding homeobox 2 through directly targeting its 3' utr and direct inhibition of zeb2 can mimic the effects of mir-200s on ipsc generation and met process. in conclusion, we found that oct4 and sox2 can directly activate the expression of a specific cluster of the mir-200 family by binding to their promoter regions, whereas the expression of mir-200s significantly repress zeb2 expression through directly targeting its 3- utr. 23386720_2 taken together, members of the mir-200 family have more significant effects on zeb2 than zeb1, suggesting that the mir-200 family mainly target zeb2. 23386720_3 consistently, the protein level of zeb2 was significantly inhibited by specific mirna mimics of mir-200 family and blocked by the corresponding inhibitors . 23386720_4 these results indicated that zeb2 may be the preferred target gene of the mir-200 family in vivo. 18577219_1 microrna-124 and microrna-137 induce differentiation of adult mouse neural stem cells, mouse oligodendroglioma-derived stem cells and human glioblastoma multiformederived stem cells and induce glioblastoma multiforme cell cycle arrest. 18577219_2 these results suggest that targeted delivery of microrna-124 and/or microrna-137 to glioblastoma multiforme tumor cells may be therapeutically efficacious for the treatment of this disease.mir-124 18577219_3 and mir-137 inhibit cdk6 expression and phosphorylated retinoblastoma levels in gbm cells. 25964525_1 figure 4. reporter activity for different exosomal mirnas and elisa for the mir-92 target dkk3 after treatment with exosomes. 26689540_1 meanwhile, overexpression of mir-222 inhibited tam chemotaxis, and mir-222 in tams inhibited 4t1 tumor growth by targeting cxcl12 and inhibiting cxcr4. 26689540_2 furthermore, mir-222 inhibited the recruitment of macrophages by targeting cxcl12 and inhibiting cxcr4 to suppress 4t1 tumor growth. 26689540_3 these findings demonstrate that mir-222 targets cxcl12 in macrophages. 26617714_2 the results indicated that abce1 is a target gene of mir-299-3p. 22767443_1 based on the previous results, we hypothesized that both abcb11 and atp8b1 are direct targets of mir-33. 22767443_2 mir-33 downregulates abcb11 and atp8b1 in both human and mouse hepatocytes. 22767443_3 here we show that both simvastatin and atorvastatin induce hepatic mir-33 expression while at the same time decrease the mrna levels of mir-33 targets abca1, cpt1alpha, abcb11 and atp8b1 . 26885264_1 we then investigated the relationship between mir-135a and txnip. 26885264_2 luciferase reporter assay demonstrated that co-transfection of mir-135a mimic decreased the txnip expression and its 3'-utr activity , while mir-135a inhibitor increased these levels , which suggesting txnip was a potential target gene of mir-135a. 26885264_3 alteration of mir-135a expression led to the regulation in 3'-utr activity of txnip in hl-1 cells. 26198058_1 experimental emt in vitro assays were performed as previously described and qrt-pcr analyses demonstrated that most of these novel candidate genes were down-regulated after overexpression of both mir-23b and mir-199a in avc explants , respectively. 26198058_2 two genes were downregulated only when overexpressed with mir-23b while g3bp2 was up-regulated after overexpression of both mir-23b and mir-199a, respectively . 26198058_3 therefore, we have identified 13 new genes modulated by mir-23b and mir199a that may be involved in the emt process. 20351690_1 both in vitro and in vivo, silencing of mir-10b with antagomirs significantly decreases mir-10b levels and increases the levels of a functionally important mir-10b target hoxd10. 20351690_2 importantly, the levels of the hoxd10 protein expressed in the primary tumors were markedly increased by antagomir-10b treatment. 20351690_3 unlike antagomir-10b-treated mice, which showed abundant, derepressed hoxd10 protein expression in primary tumors , mice treated with antagomir-10b_mm showed low to undetectable hoxd10 expression in their primary tumors , levels comparable to those observed in pbs-treated mice . 25008898_1 in conclusion, our results highlight the upregulation of mir-758 expression by hcv as a novel mechanism contributing to downregulation of tlr3 and tlr7 in patients with hcv infection. 26876575_1 in addition, the dual-luciferase reporter assay showed that mir-218 directly targeted the 3'-untranslated region of heme oxygenase-1 , and further study confirmed an increase of ho-1 in hg-treated podocytes transfected with anti-mir-218. 26876575_2 these results confirmed that ho-1 3'-utr is a direct target of mir-218. 26876575_3 fig. 2. heme oxygenase-1 is a direct target of mir-218. 26876575_4 taken together, these results suggested that mir-218 mediates hg-induced ho-1 expression, and that ho-1 is the direct target of mir-218. 22713463_1 we further demonstrated that downregulated mir-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 . 26790441_1 afterwards, using luciferase reporter assay and gene expression analysis at bothmrna and protein levels, vegfr2 and fgfr1 were validated as mir-129-1 and mir-133 targets. in the current study, we report that mir-129-1 and mir-133 suppress angiogenesis in huvecs proliferation, cell viability, and migration ability by targeting the angiogenesis factors vegfr2 and fgfr1, respectively. 26790441_2 these results indicate that vegfr2 and fgfr1 are direct targets of mir-129 and mir-133, respectively. 26790441_3 these results confirmed luciferase assay results and indicated that mir-129-1 and mir-133 target vegfr2 and fgfr1, respectively. 26790441_4 in the current study, we identified the novel angio-mirs of mir-129-1 and mir-133 as negative regulators of angiogenesis via targeting vegfr2 and fgfr1. 21159652_1 paxillin gene mutations are associated with lung adenocarcinoma progressionand pxn is known to be a targetgene of microrna-218 . 21159652_2 these results suggest that pxn expression in lung tumors is negatively associated with mir-218 expression. 21159652_3 these results suggest that mir-218 may modulate pxn expression by directly targeting its 3'-utr in lung cancer cells. 21159652_4 figure 2. mir-218 suppressed pxn expression by directly targeting its 3'-utr. 26232617_1 these results suggested that high glucose-induced impaired tube formation included scf downregulation by mir-34c . 26232617_2 these results suggested that high glucose-induced mir-34c suppressed scf, and these event consecutively induced klf4 . 22476851_1 microrna-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer. 22476851_2 mir-30a negatively regulated vimentin expression by binding to the 3'-untranslated region of vim. the finding that mir-30a downmodulates vimentin expression might provide a therapeutic targetfor the treatment of breast cancer. 22476851_3 these results indicate that the region from 178 to 184 is the important site within the 3'utr of the vim gene that is required for mir-30a binding. 21623795_1 direct interaction of mir-743a with mdh2 was demonstratd with a luciferase based assay. 21623795_3 figure 4 mir-743a inhibited luciferase activity of a dual luciferase reporter containing mdh2 3- utr. the firefly luciferase was fused to the entire mdh2 mrna 3- utr. 21623795_4 our data also show that mir-743a negatively regulates mdh2 at the post-transcriptional level by directly targeting the mdh2 3- utr. 19458054_1 the levels of p21 were significantly attenuated following infection with ad-p53/mir-p21. 19458054_2 in colorectal and hepatocellular carcinoma cells, infection with ad-p53/mir-p21 augmented apoptosis as compared with an adenovirus that expressed p53 alone . 26506419_1 furthermore, the liver-specific mirna, mir-122, inhibits csc phenotypes by regulating glycolysis through targeting pdk4. 26506419_2 while mir-122 is markedly down-regulated in cd133 cells, ectopic expression of mir-122 inhibits glycolysis leading to decreased stemness gene expression and reduced spheroid formation. 26506419_3 our further experiments demonstrate that pdk4 is a direct target of mir-122. 26506419_4 these results demonstrate that mir-122 inhibits cd133 cscs, at least in part, through glycolytic reprogramming via targeting pdk4 26571175_1 as shown in figure 4c,d, over-expression of mir-221 reduced both timp-2 protein and mrna levels in lf cells. 25714029_1 collectively, our data showed that mir-188-5p negatively modulated laptm4b expression by directly binding to its 3'-utr. 23936434_1 to initially explore the mechanism by which 14-3-3delta is down-regulated in spina bifida, we measured mir-7, mir-375 and mir-451 in normal and defective spinal cords at e12, e13 and e15. in subgroup 2, the expression of mir-7, mir-375 and mir-451 was similar to that in controls . 26547929_1 the above results indicated that il-6, ap3b1, tc10, onecut2, igf2bp1, myo1d and anxa2 are potential target genes of mir-9 in hcc. 25640197_1 mir-429 was down-regulated in oscc tissues, and mir-429 overexpression inhibited oscc cell lines growth and vice versa. 25640197_2 further, we found that mir-429 could inhibit zinc finger e-boxbinding homeobox 1 expression, and that mir-429 and zeb1 expression in oscc tissues were negatively correlated. 21400511_1 foxc1 was determined as a targetgene of mir-204, and two binding sites in the 3'-untranslated region were validated by dual luciferase reporter assay. 21400511_2 based on our qrt-pcr detection and correlation analysis, mir-204 and foxc1 expressions were inversely related in eecs. 21400511_4 we conclude that mir-204 regulates foxc1 expression through interaction with bs1 and bs2. 21400511_6 combined with our substantial evidence on mir-204 inversely regulated foxc1 expression, we propose that mir-204-regulation of migration of eec cells is mediated to a large extent through downregulation of foxc1 19878981_1 let-7 microrna directly inhibits expression of il6. 19878981_2 several lines of evidence indicate that let-7a directly target il6 mrna through binding its 3'-utr. 19878981_3 thus, let-7a microrna inhibits il6 expression both directly through its 3'-utr and indirectly by an interaction with ras that leads to a reduction in nf-kappab activity. 19878981_5 after 30 days, the tumors were extremely small in size, and cells taken from these tumors had low expression of lin28b and il6 and high levels of let-7 . 23873704_2 among them, mir- 382 is an important regulator and participator in alcohol intake via its direct target gene drd1 and its downstream signal molecule deltafosb. 20833714_3 online programs, we identified four mirnas, mir-138, mir-148a, mir-185, and mir-339-5p, with predicted binding sequences tokdm6b 3- utr . 20833714_4 figure 4. kdm6b is targeted by mir-148a, mir-185, and mir-339-5p. 11884032_1 mutation experiments indicated that lin-4 acts through the 3'utr of lin-28, and lin-28 is directly regulated by the lin-4 rna.first, lin-4 affects developmental timing through downstream targets other than lin-14. 11884032_2 second, lin-28 contains a 15 nt lce in its 3'utr that is predicted to be complementary to the lin-4 rna.lin-28 lce resembles each of the seven lin-4-complementary elements in the lin-14 3'utr that are necessary for the translational regulation of that gene by lin-4. 11884032_3 fourth, both lin-4 and the single lce of lin-28 are necessary for the stage-specific down-regulation of lin-28. 22684256_2 first, mir-129-3p downregulates cp110 probably to facilitate the basal body formation. 22684256_3 figure 1 mir-129-3p is an important ciliogenic regulator that target cp110. 22684256_4 mir-129-3p specifically targeted the 3' utr of human cp110 mrna. 26807173_1 bioinformatic analysis showed that cxcl2 might be regulated by mir-532-5p. 26807173_2 we next examined whether mir-532-5p could regulate endogenous cxcl2 expression in the above two cell lines. 26807173_3 compared with the control, endogenous cxcl2 mrna levels were down-regulated when cells were transfected with mir-532-5p . 26807173_4 the protein levels cxcl2 was reduced in the hepg2 and pg5 cells with mir-532-5p overexpression. 26807173_5 we further analyzed the relationship between cxcl2 and mir-532-5p, and found that cxcl2 expression was negatively related to mir-532-5p expression in liver cancer tissue samples. 26807173_6 the result indicated that mir-532-5p inhibited cxcl2 activated stat3 signal pathway. 26176806_1 mtdh was a direct target of mir-302c-3p which inhibited its expression via binding to its 3'-utr. . in our study, we found that mtdh is a direct target of mir-302c-3p. 22479460_1 furthermore, ectopic expression of mir-34c reduces atf1 protein expression without affecting atf1 mrna level via directly binding to atf1's 3'utr, indicating that atf1 is one of mir-34c's target genes. 26654778_1 microrna array analysis revealed that mir-27b expression was up-regulated in hfd mice, and luciferase assay confirmed the direct interaction between mir-27b and cx40 3'-utr. 26654778_2 mir-27b interacted with cx40 3'-utr. 26654778_3 we confirmed that mir-27b directly bound to the 3'-utr of cx40 by luciferase reporter assay. 21527938_1 however, we show that mir-19-mediated regulation of antiapoptotic rhob expression requires the binding of human antigen r , an au-rich element binding protein, to the 3'-untranslated region of the rhob mrna. 23222811_5 furthermore, h19 associated with the protein complex hnrnp u/pcaf/rnapol ii, activating mir-200 family by increasing histone acetylation. 23222811_6 the results demonstrate that h19 can alter the mir-200 pathway, thus contributing to mesenchymal-to-epithelial transition and to the suppression of tumor metastasis. 25976060_1 using the luciferase reporter system, we then detected that mir-124 directly binds the mrna encoding bim. 25976060_2 indeed, cells transfected with mir-124 mimics induced a reduction in luciferase activity . in our study, we found that downregulating bim by mir-124 or si-bim rna reduced bax translocation to lysosomal membrane in mpp+-intoxicated cells . 25416050_1 mir-363 sensitizes cisplatin-induced apoptosis targeting in mcl-1 in breast cancer. 26138477_1 these striking similarities between deltartl1 and deltamir-127/deltartl1 placentae suggest that mir-127 specifically acts upstream of rtl1 during placental development. 26138477_2 rtl1 is the main target gene of mir-127 for placenta development. 26799586_1 cyclin d1 was identified as a target of mir-1296 action. 26799586_2 our results demonstrate a novel tumor suppressor role for mir-1296 in triple-negative breast cancer cell lines, identify ccnd1 as its target of action, and demonstrate a potential role for mir-1296 in sensitizing breast cancer cells to cisplatin. 26799586_3 this report describes, for the first time, a functional role for mir-1296 in triple negative breast cancer, identifies ccnd1 as a target of mir-1296 action, and demonstrates the potential for mir-1296 to sensitize tnbc cells to chemotherapeutic agents. 26799586_4 our results demonstrated that mir-1296 directly targets the 3'-utr of ccnd1. 22300508_1 forkhead box proteins are a family of important transcription factors and foxo1 is a target of mir-182. 22300508_2 figure 7. foxo1 is a target of mir-182 in the mouse cho cells were transfected with the pcdna3.1-mir-182 22300508_4 as the 3' utr of foxo1 is inserted downstream of the luciferase orf, specific binding to mir-182 prevents luciferase reporter gene expression ; however, mutation of the foxo1 binding site decreases specific binding to mir-182 and restores luciferase activity indicating that mousefoxo1 is a target of mir-182. 22300508_6 thus, there is a concomitant increase in mir-182 expression and a posttranscriptional decrease in foxo1 in both cardiomyocytes and cd3+ t cells posttransplant. 23800944_1 mir-874 inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer.down-regulation of bcl-2, mt1-mmp, mmp-2 and mmp-9 and upregulation of caspase-3 activity and bax were involved in mir-874 inducing cell apoptosis, and inhibiting migration and invasion. 26461141_1 stat6 is a direct target of mir-361-5p and promotes bcl-xl expression. 26461141_2 the 3'-utr of stat6 mrna was identified as a target of mir-361-5p. in the present study, the mrna and protein levels of stat6 were depressed by transfection with mir-361-5p mimics. 20080624_1 a significant reduction in the luciferase activity of the reporter construct containing the atm 3'utr was observed in the presence of mir-421, whereas no changes were noted in the luciferase activity of the unmodii ed construct with mir-421 expression . 20080624_2 atm mrna levels were measured by quantitative real-time pcr and were not decreased in the presence of mir-421 , suggesting that mir-421 down-regulates atm at a translational rather than transcriptional level. 20080624_3 taken together, these amo-atm experiments suggest that the effect of mir-421 on the cell cycle s-phase checkpoint and radiosensitivity is mediated through atm. 22995917_1 of the mrna targets and mir mimic combinations tested, pdgfra mrna levels were significantly down-regulated by mimics for mir-130b and -218, and cpeb4 mrna levels were reduced following electroporation of let-7b mimics . 22995917_3 reduction in pdgfra mrna levels by mir-130b and -218 was also evident by ish, whereas a control mir had no effect on pdgfra ish staining intensity. 26822433_1 we found that pten gene constitutes a mir-29 binding domain on its 3'-utr . 26822433_3 one was to express the 3'-utr of pten gene which includes mir-29 binding domain .the 26822433_4 other was to express a mutated pten 3'-utr sequence without mir-29 binding domain . 26822433_5 suggesting that pten is the downstream target of mir-29. 26822433_6 these results demonstrated that pten was closely associated with hg condition and subsequent mir-29 regulation in arpe-19 apoptosis. 26822433_7 our results clearly demonstrated that inhibiting pten reversely regulated the protection of mir-29 downregulation on hg-induced apoptosis in arpe-19 cells. 22551553_2 mir-146a upregulation and notch1 repression were determined to be responsible for the reduced il-12p70 production in tlr9-triggered wild-type dcs compared with that in cd11b-deficient dcs. 22551553_3 therefore, cd11b and downstream mir-146a may be new negative regulators for dc cross-priming by suppressing notch1 expression and il-12p70 production. 22551553_4 to verify whether notch1 3'-utr was directly targeted by mir-146a, we constructed a reporter plasmid containing notch1 3'-utr and found that its expression was inhibited by mir-146a cotransfection, whereas the seed region-mutated construct failed to be inhibited by mir-146a expression . 22551553_5 this result suggests that notch1 is directly targeted by mir-146a. 22551553_6 together with the result that cpg-odn enhances mir-146a expression in wild-type dcs and mir-146a enhancement is abolished in cd11b-deficient dcs, these data further confirm that cd11b represses cpg-odn-搕riggered il-12p70 production in dcs via upregulating mir-146a and targeting notch1. 26265132_3 this restrained cell death may be associated with several downregulated genes in our dataset that we functionally validated for the first time as targets genes of mir-29b and mir-223, including eva1a, layna, si:ch211-51a6.2 , smoc1 and es1-like homolog, sb:cb252. 26653555_1 luciferase reporter assay confirmed that mir-30b targeted erg. 26653555_2 erg is a target gene of mir-30b. 26653555_3 we also demonstrated that mir-30b targeted erg, with the results showed that mir-30b mimic significantly decreased erg mrna and protein expression while mir-30b inhibitor elevated their levels in sw1353 cells. 20816961_1 furthermore, as shown by western blot , knockdown of mir-24 using anti-mir-24 lna increased the protein level of dnd1 in um2 cells. 20816961_2 similarly, cdkn2a, a known target of mir-24 , was also up-regulated by anti-mir-24 lna treatment. 20816961_3 in contrast, ectopic transfection of mir-24 reduced the protein levels of both dnd1 and cdkn2a in um2 cells . 21376256_1 there was a significant increase in luciferase activity in the cells transfected with the wild-type prl-tk plasmid, in contrast to those transfected with the mutant one, indicating that mir-21 promotes bcl-2 expression by binding directly to the 3'utr of bcl-2 mrna. 26079878_1 we discovered that higher mrna level of mir-138 and reduced expression of sirt1 were observed in smcs separated from db/db mice and in smc lines c-12511. 26079878_2 moreover, luciferase report assay showed that the activity of sirt1 3' -utr was highly increased by mir-138 inhibitor and reduced by mir-138 mimic. 26079878_3 taken together, these findings indicated that mir-138 could regulate the expression of sirt1 in smcs. 26564600_2 these data indicated that stk35 is a direct target of mir-377. 22721728_1 bioinformatics' algorithms predicted mir-195 binding sites within the beta-site app cleaving enzyme 1 3'-untranslated region , and we found the level of mir-195 to be negatively related to the protein level of bace1 in samp8 mice. 22721728_2 thus, we demonstrated that mir-195 could downregulate the level of a-beta by inhibiting the translation of bace1. 22721728_3 these results suggest that mir-195 might regulate the bace1 mrna translation or decay process, through binding site 1 . 22721728_5 these data together indicate that mir-195 negatively regulates bace1 translation and a production in vitro. 22449978_1 we also confirmed that oncogenic tnks2 is directly upregulated by mir-20a. in addition, tnks2 is positively regulated by mir-20a and similarly promotes migration and invasion in hela and c-33a cells. 22449978_2 these results suggested that mir-20a could directly bind to the 3' utr and specifically promote the expression of tnks2. 22449978_3 these data revealed that mir-20a can positively regulate tnks2 mrna and protein expression. 22449978_4 together, these data suggest that mir-20a modulates the translation of tnks2 mrna via binding sites in its 3' utr and promotes the expression of tnks2 mrna and protein in hela and c-33a cells. 21164520_1 western blot and 3'utr reporter assays confirmed runx2 as a direct target of mir-335 in hmscs. 21164520_2 a western blot analysis of runx2 demonstrated that its protein levels are reduced in hmscs by mir-335 exogenous overexpression . 21164520_3 to determine whether mir-335 directly modulates runx2 expression levels in hmscs, we cloned the full-length runx2 3'-utr downstream of the renilla luciferase gene as a reporter, and assayed its expression in hmscs transfected with a synthetic precursor or a specific inhibitor of mir-335. 21164520_4 these results indicate that mir-335 controls runx2 expression in hmscs by direct binding to its 3'-utr. 21164520_5 the results of these experiments showed a significant reduction of runx2 expression levels in the cells transduced with the lentiviral vector encoding mir-335, compared with those transduced with a control lentiviral vector, which is in good agreement with the rest of the data indicating that runx2 is a target of mir-335 in hmscs. 21927029_1 a 3'-utr reporter assay in hek-293t cells also showed that among these three putative targets, only the foxp1 reporter was significantly repressed by mir-504 . 21927029_2 a similar result was obtained from the same experiment performed in sas cells , suggesting the foxp1 as an important target of mir-504 in ctgf regulation machinery. 21927029_3 collectively, these data support that suppression of mir-504 by ctgf, resulting in upregulation of foxp1 expression contributes to ctgf-mediated inhibition of oscc invasiveness. 25645685_2 here, we found that amp-activated protein kinase and creb are oppositely regulated in mouse primary hippocampal neurons impaired by hypoxia-hypoglycemia. ampk overexpression reduced the creb level by upregulating sirt1 and was negatively posttranscriptionally regulated by mir-134, suggesting a negative regulatory role of ampk in the expression of creb. 19738602_3 a prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic mir-16 to tumor cells on bone tissues in mice when injected into tail veins. in the therapeutic bone metastasis model, injection of mir-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. 19738602_4 cell model studies indicate that mir-16 likely suppresses prostate tumor growth by regulating the expression of genes such as cdk1 and cdk2 associated with cell-cycle control and cellular proliferation. 22991213_2 the tumor-suppressive mir-125b served as a negative regulator of suv39h1. in conclusion, we identified suv39h1 as an important oncogene in hcc, and aberrant suv39h1 up-regulation was partly attributed to the under expression of mir-125b. 22991213_3 suv39h1 was negatively regulated by mir-125b in human hcc. 22991213_4 taken together, our data suggested that suv39h1 up-regulation is contributed by the underexpression of mir-125b in hcc. 22991213_5 furthermore, mir-125b-overexpressing hcc cells showed a profound reduction of endogenous suv39h1 expression at both messenger rna and protein levels . 22267480_1 knockdown of mir-92a stimulated expression of klf4 protein, but expression of klf2 protein remained unchanged . 22267480_2 however, knock-in of mir-92a suppressed transcript expression and protein expression of both klf4 and klf2. 22267480_3 overexpression of mir-92a precursors, but not the scrambled sequence, significantly inhibited the activity of klf4 3'-utr- or klf2 3'-utr-containing luciferase in hek 293 cells without effect on the control luciferase. 22267480_4 collectively, the data demonstrate the presence of functional mir-92a binding site in the 3'-utrs of both human klf4 and klf2. 22267480_5 the sensitivity to mir-92a of the less evolutionarily conserved binding site identified in the 3'-utr of klf4 suggests an additive contribution to klf4 regulation. 22267480_6 renilla luciferase with putative let-7b binding sites cloned from lin-24 3'-utr was unresponsive to mir-92a knock-in . 22267480_7 moreover, the functional assay demonstrated the responsiveness of the less evolutionarily conserved mir-92a putative binding element, consistent with measurements in constructs expressing human klf4 full-length 3'-utr. 26554827_1 stable expression of mir-885-5p causes severely reduced igf1r transcript levels compared with cells expressing mir-scr . 26554827_2 to support direct suppression, we cloned 3- utr fragments of igf1r mrna containing the mir-885-5p-responsive elements at position 1407-1414, 1833-1839 , and 6965-6971 into reporter plasmid and examined luciferase activity . 26554827_3 increasing amounts of mir-885-5p clearly blocked reporter activity regulated by both 3- utr elements, demonstrating a strong inhibitory effect of mir-885-5p on igf1r expression. 26554827_4 together, these results provide a molecular mechanism that is responsible for inhibition of igf1r by tap73, and indicate that dnp73 activates igf1r signaling via suppression of the tap73-mir-885-5p axis. 20338660_2 col1a2 was experimentally validated as a direct target of let-7g. 20338660_3 moreover, addition of col1a2 counteracted the inhibitory effect of let-7g on cell migration. 20338660_6 taken together, these results indicate that let-7g directly target col1a2, and that a single site within col1a2 mrna is sufficient for let-7g-mediated gene silencing. 26498692_1 in addition, we identified ppm1f as a direct target of mir-149 whose expression was negatively correlated with the expression of mir-149 in hcc tissues. 26498692_2 to conclude, our data indicate that mir-149 negatively regulates the expression of ppm1f by directly targeting its 3'-utr. 26498692_3 to further elucidate the underlying molecular mechanism by which mir-149 is involved in hcc metastasis, we predicted the putative targets of mir-149 using bioinformatics and validated that ppm1f is a direct downstream mediator of mir-149 through luciferase reporter and western blot assays. 26506238_1 dhfr is a downstream target of mir-192 26802080_1 thus, it is quite possible that human ahr is a direct target of mir-124. 26802080_2 these results unequivocally demonstrate that mir-124 directly recognizes the 3- utr of ahr 23146892_1 furthermore, hydrogen peroxide treatment suppressed mir-199a and mir-125b expression , suggesting that ros inhibit mir-199a and mir-125b expression. 23146892_2 overexpression of mir-199a greatly decreased erbb2 and erbb3 expression in both cell lines, whereas mir-125b decreased erbb3 protein level, but not erbb2 expression . 23146892_3 this indicated that erbb2 is regulated by mir-199a, whereas erbb3 is regulated by both mir-199a and mir-125b. 25482402_2 these data indicate that mir-200a may negatively regulate macc1 expression by directly targeting its 3'-utr. 25060662_1 going along with this systemic treatment with mir-144 increased p-akt, p-gsk3-beta and p-p44/42 mapk, decreased p-mtor level and induced autophagy signaling, and induced early and delayed cardioprotection with improved functional recovery and reduction in infarct size similar to that achieved by ripc. 26477824_1 transfection with pre-mir-92a caused down-regulation of itga5 and mek4 mrnas almost 3 and 2 folds, respectively, whereas transfection with anti-mir-92a did not significantly affect their mrnas 20514397_1 we also show that mir-1226 interacts with the muc1 mrna 3'utr and that mir-1226 downregulates endogenous muc1 protein levels. 20514397_2 these findings indicate that mir-1226 interacts with the muc1 3'-utr and suppresses muc1 translation. 26738864_1 overexpression of mir-488 suppressed the pax6 mrna expression in hgc-27 cell. 26738864_2 moreover, we also demonstrated that the ectopic expression of mir-488 inhibited the protein expression of pax6. 20236612_2 here we show for the first time that in s-ibm muscle biopsies, bace1-as transcript is significantly increased and is accompanied by an increase of bace1 mrna. 20236612_3 our present findings suggest that the increased bace1 protein results, at least partially, from the increased transcription of bace1 mrna, quite likely driven by bace1-as. 25071021_1 herg1 is a direct target of mir-96 in pancreatic cancer cell lines. 25071021_2 this result indicates that mir-96 can suppress the herg1 expression in vivo and further demonstrates that herg1 is a direct target of mir-96. 25503932_1 in vitro assays showed that egfr and raf-1 are direct targets of mir-7, which potently suppressed the proliferation of crc cells, and, interestingly, that the growth inhibitory effect of each of these was enhanced by cetuximab. 25503932_2 binding of mir-7 to the 3'-utr of egfr mrna and the 3'-utr of raf-1 mrna was analyzed by using a luciferase assay. 25503932_3 these data suggest that the 3'-utrs of both egfr and raf-1 are direct functional targets of mir-7. 26864305_1 conversely, mir-223 inhibition led to increased total hdac and hdac2 activity, however, without reaching statistical significance. 26864305_2 similarly, treatment with anti-mir-223 led to a reduction of the mrna level of cx3cl1. 26864305_3 transfection of hpaec with mir-223 decreased the mrna levels of hdac2 to 0.86 卤 0.15 p' 0.099 whereas mir-223 inhibition significantly increased mrna levels of hdac2 by 1.08 卤 0.036-fold p' 0.007 as compared to control cells. 26485754_1 mir-744 activates wnt/-beta-catenin pathway by targeting sfrp1, gsk3-beta, and tle3. 26485754_2 however, neither mir-744 overexpression nor mir-744 inhibition has effect on the mrna levels of sfrp1, gsk3-beta, and tle3, suggesting that the inhibitory effect of mir-744 on sfrp1, gsk3-beta, and tle3 was regulated at the post-transcriptional level. 26485754_3 mir-744 directly targets sfrp1, gsk3-beta and tle5. 25654102_2 ppp2r2a was a functionally important target of mir-136 and was involved in the tgf--beta1 regulated proliferation of hacat cells. 19696787_2 furthermore, overexpression of a mir-34a precursor in tig3 tert/螖b-raf:er cells had little effect on myc at the mrna level , suggesting post-transcriptional regulation at the level of translation. 19696787_3 strikingly, mir-34a overexpression resulted in marked downregulation of endogenous myc protein, indicating that mir-34a can affect cell proliferation through repression of myc. 19696787_4 thus, our data show that mir-34a regulates myc through direct binding to its 3'-utr. 25550792_1 the luciferase reporter that contained the dnajc13 3- utr was significantly suppressed by pre-mir-193b, whereas the mutated reporter was not affected . 25550792_3 in conclusion, our experiments have shown that mir-193b is a novel tumor suppressor in breast cancer through regulation of at least the transcription factor dnajc13 and the expression of oncogene rab22a. 26041742_1 a signal transducer and activator of transcription 3 -activating stromal factor, identified as interleukin -6, was found to upregulate microrna -17 and mir-19a, target tlr7 and tnfa messenger rna, and induce a state of tolerance to tlr7-agonists in cll cells. 26041742_2 luciferase assays with nih-3t3 cells transiently transfected with reporter genes containing these seed sequences, along with mir-17 or mir-19a expression vectors were consistent with regulation of tlr7 and tnfa by mir-17 and mir-19a. 26041742_3 here, we suggest that il-6-mediated induction of mir-17 and mir-19a may slow cll progression by downregulating expression of tlr7 and tnfa in cllcells and inhibiting their proliferative responses toendogenous tlr7 ligands. 22069160_1 in silico analysis identified a mir-433 binding domain in the mad2 3'utr, which was verified in a series of experiments. 22069160_2 the ovarian cancer cell line a2780, which expressed the highest level of mad2 mrna and protein expression levels , displayed the lowest mir-433 expression levels . 22069160_3 when comparing the a2780 cell line with the other ovarian cancer cell lines, lower mad2 mrna and protein levels were associated with concomitant higher mir-433 expression levels . 22069160_4 finally, the previously described pmir-report mirna expression reporter vector system for measuring mrna-microrna interactions was also used to investigate whether mir-433 interacts with the mad2 3'-utr. 22069160_5 overall, these experiments demonstrate a functional interaction between mir-433 and mad2 3'-utr. 26796133_1 thsd7a was validated as a direct target of mir-210 using quantitative real time pcr , western blotting, and dual luciferase assays in htr8/svneo cells. 26796133_2 the targeting and repression of thsd7a by mir-210 were validated by a luciferase reporter assay in a human placental trophoblast cell line, htr8/svneo. 26796133_3 the data validated thsd7a as a target gene of mir-210 in human trophoblast cells, and indicated that the 5182-5189nt region of 3- utr in thsd7a gene is a binding site for mir-210. 26377202_1 these results identified sox4 as a new target gene of the mir-212/132 cluster in mda-mb-231 and t47d cells. 26377202_2 a reciprocal correlation was identified between ahr agonists-induced mir-212/132 and the pro-metastatic sry-related hmg-box4 , and a new specific binding sites for mir-212/132 were identified on the untranslated region of sox4. 26870245_1 these results indicated that mir-135b may downregulate the expression of stat6 through the mir-135-binding sequences located at the 3'-utr of the stat6 gene. 20160723_1 the mir-133a as well as mir-145 had the targetsequence of fscn1 mrna by the database search, and both micrornas repressed the mrna and protein expression of fscn1. 20160723_2 the luciferase assay revealed that mir-145 and mir-133a were directly bound to fscn1 mrna. 23508904_2 linear correlations were found between microrna-122 or microrna-22 and hbsag levels and alt levels.serum 23508904_3 microrna-122 and microrna-22 levels were analyzed in 198 patients with chronic hbv who underwent liver biopsy and were compared with quantitative measurements of hbsag, hbeag, hbv dna, and other clinical and histological findings. 23508904_4 levels of serum microrna-122 and microrna-22 were determined by reverse transcription-taqman pcr. 26025955_1 connexin 43 was validated to be a functional target of mir-1298 that was involved in the mir-1298-mediated cellular effects. 26025955_2 finally, lentivirus-mediated delivery of mir-1298 and its target cx43 into a rat carotid balloon injury model indicated that re-overexpression of mir-1298 significantly decreased neointimal formation by targeting connexin 43. the results confirmed that cx43 is a direct target of mir-1298. 26025955_3 taken together, these data indicate that cx43 is a direct target of mir-1298 and was involved in mir-1298-induced cellular effects. 26918449_1 furthermore, malat1 acted as an endogenous potent regulator by directly binding to mir-124 and down-regulating mir-124 expression. 26918449_2 these data show that malat1 inhibited mir-124 expression in breast cancer cells. 26918449_3 these results reveal that malat1 may interact with mir-124 by this putative binding site. in this study, we found that malat1 suppressed mir-124 expression in breast cancer, which inverted the inhibitory effect of mir-124 on the tumor growth of breast cancer cells in vitro and in vivo. 26131134_1 as demonstrated with qpcrs, mrna levels of p27 were down-regulated by overexpression of mir-222 while remained unchanged by mir-222 inhibition . 26131134_2 the protein levels of p27 were decreased by mir-222 overexpression while increased by mir-222 downregulation in h460 cells, indicating that p27 might be a target gene of mir-222 in h460 cells. 23373993_1 these results suggest that ato -induced apoptosis in retinoblastoma cells is part mediated by decreasing expression of mir-376a, which subsequently increased caspase-3 expression. 26409044_1 the three series of experiments were designed to explore if mir-100 directly targeted the 3'-utr of mtor. 26409044_2 these results support that mtor gene is the downstream target of mir-100. 26409044_3 mir-100 directly targets the 3'-utr of mtor through mres. 21256239_1 acts as a sponge/targetmimic for mir-372 reducing its expression and activity. 26374689_2 we confirmed that jam-a mrna and protein levels were downregulated in cscs after mir-145 introduction compared with cells containing nt mimics . 22012620_1 we show that in addition to its role in tgf--beta signaling, mir-302/367 promotes bone morphogenetic protein signaling by targeting bmp inhibitors tob2, dazap2, and slain1. 23125218_1 mir-152 represses dnmt1 expression by targeting 3'-utr. 23125218_2 moreover, transfection of mir152 resulted in significant decrease of dnmt1 expression at both mrna and protein levels 锛宨ndicating mir-152 is involved in both dnmt1 mrna degradation and posttranscriptional regulation. 23125218_3 thus, the in silico identified sequence for mir-152 binding in dnmt1 3'-utr was functionally validated as a bona fide mir-152-binding site. in all, these results suggest that mir-152 directly binds the dnmt1 3'-utr and inhibits its expression. 21478429_2 as shown in figure 5b, all these mirnas, with the only exception of mir-155, were able to down-regulate the myc 3'-utr in reporter assays. 26512921_1 mir-29b directly targets and thus negatively regulates akt2 and akt3. 23133627_1 a significantly negative effect on luciferase activity was observed on the 3' utr of ches1 in the presence of mir-574-5p, such repression disappeared when the predicted targetsite in the 3' utr of ches1 was mutated . 23133627_2 these results indicated that ches1 was a bona fide target of mir-574-5p in regulating tlr9 signaling enhanced tumor progression of human lung cancer. 23133627_3 these findings were in line with our above data which demonstrated that ches1 was a predominate targetfor mir-574-5p to confer the enhanced tumor progression induced by tlr9 signaling in human lung cancer. 25658689_1 a detailed analysis of target proteins by available literature identified among many other proteins grhl3 to be a probable target of mir21. 25658689_2 western blot analysis of mir21 target protein grhl3 showed a sharp decrease in both dio+bdcm group and dio+ccl4 group as compared to dio only group . 25658689_3 mir21 upregulation and its corresponding targeting of grhl3 is known 19441017_1 ccnd3 and e2f3 were identified as functional target of mir-195 in glioblastoma cells. 19441017_2 we next examined the correlation between the decreased expression of mir-195 and the overexpression of e2f3, cyclin d1, and cdk6, the target of mir-195, in hcc tissues. 19441017_3 e2f3, cyclin d1, and cdk6 were analyzed by immunohistochemistry in the same set of specimens shown in fig. 1. taken together, these data imply that mir-195 may attenuate the expression of cyclin d1, cdk6, and e2f3 by directly targeting their 3- utrs. 25334070_3 furthermore, inhibition of egfr showed similar effects to mir-7 enforcement in 3ll cells. 22114071_1 our data suggested that the rs2735383g>c variation contributes to an increased risk of lung cancer by diminishing gene's expression through binding of microrna-629 to the polymorphic site in the 3'-utr of nbs1 gene. 22114071_2 as shown in figure 2b, the mimics of mir-629 could suppress the mrna expression of nbs1 gene in a549 cells with rs2758383cc genotype , and the inhibitors of mir-629 could reverse and upregulate the expression of nbs1 in a549 . 22114071_3 the stronger effect of mir-629 on modulating nbs1 in a549 than that of nci-520 cell lines indicated that the mir-629 specially binds rs2758383c allele of the 3' utr of nbs1 gene and suppress the expression of the nbs1 gene in vitro. in conclusion, in these two independent hospital-based case-control studies of lung cancer, our data suggest that the functional polymorphism rs2735383g.c in the 3' utr of nbs1 gene confers an increased risk of lung cancer via the binding of microrna hsamir-629. 26826505_1 target gene searching for faslg was performed by using multiple databases suggested that faslg might be a potential target of let-7e-5p due to the presence of a putative binding site within its 3'-utr. 26826505_3 if the 3'-utr faslg was mutated in the luciferase reporter vector, let-7e-5p agomir could not decrease luciferase activity. 26826505_4 epcs transfected with let-7e-5p agomir showed significantly decreased faslg protein expression, while epcs transfected let-7e-5p antagomir showed significantly increased faslg protein expression. 26826505_5 collectively, these results indicate that faslg is the target of let-7e-5p in epcs. 25149530_2 these results suggest that fgf2 and fgfr1 are direct targets of mir-497. 25149530_3 dual luciferase reporter assays and western blot confirmed fgf2 and fgfr1 as direct targets of mir-497. 25149530_4 however, our study provides the first findings indicating mir-497 regulation of fgf2 and fgfr1. 22272270_1 among the selected mirnas, mir-221 was significantly downregulation by rsv and its transfection in bronchial epithelial cells maximally inhibited gene and protein expression of ngf and trka, increased apoptotic cell death, and reduced viral replication and infectivity. 22558405_1 furthermore, we identified two oncogenes, nras and pim3, as downstream target of mir-124, one of the down-regulated mirnas; and a tumor suppressor, csmd1, as a downstream target of mir-10a and mir-10b, two of the up-regulated mirnas. 22558405_2 these results suggest that both mir-10a and mir-10b repress csmd1 expression through the predicted targeting sites in csmd1 3'-utr. 23936160_2 however, since investigating this interesting phenomenon is outside the scope of this paper, we decided to study homer-1b as its 3'-utrs could be greatly silenced by mir-3906, both in vivo and in vitro. 23936160_3 these lines of evidence suggest that the endogenous mir-3906 in zebrafish embryos can specifically silence luc expression through the 3'-utr from homer-1b mrna. 18583325_1 mir-9 and let-7a functionally targeted specific binding sites in the 3' untranslated region of prdm1/blimp-1 mrna and repressed luciferase reporter activities through repression of translation. 18583325_3 over-expression of mir-9 or let-7a reduced prdm1/blimp-1 levels in u266 cells by 30% to 50%, whereas simultaneous inhibition of their activities in l428 cells resulted in an approximately 2.6-fold induction in prdm1/blimp-1. 26716859_2 thus, runx1 is a direct target of mir-215 through binding to 3'-utr of runx1. 26716859_3 several target genes regulated by mir-215 in different cancers have been reported , and we observed that runx1 is a direct target of mir-215 as evidenced by the fact that ectopic expression of mir-215 reduced luciferase activity of the runx1 promoter and mir-215 downregulated runx1 expression . 26284486_2 a. western blotting of mir-21 target genes of reck, pdcd4 and pten following mir-21 inhibition at 48 h. 26755202_1 these results suggested that il-10 was the direct target of let-7i 21213367_1 the down-regulation of let-7e and mir-99b by anti-mir mirna inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative target,hmga2 and smarca5, suggesting that these molecules have a potential oncogenicrole. in line with this assumption, real-time rt-pcr and immunoblotting demonstrated that the transfected anti-mirs enhanced the expression of hmga2 and smarca5 in hs-sy-ii cells . 25055875_1 we used a combination of bioinformatics and experimental techniques to demonstrate that the mir-204 is a direct negative regulator of ezrin. in this study, we establish that mir-204 is a direct mirna regulator of human ezrin. 25055875_2 these results provided experimental support to the prediction that the mir-204 response element is located in the 3 ' utr of ezrin. 25055875_3 we found that ezrin protein expression is modulated by mir-204, and this regulatory effect is driven by mir-204 through conserved seed matches within the 3 ' utr of ezrin. 23431408_1 demonstrating that mir-181b can specifically targetthe igf-1r 3'-utr by binding to the seed sequence. 23431408_3 moreover, for the first time, we showed that igf-1r was up-regulated in glioma specimens and was inversely correlated with mir-181b levels. 23431408_4 these results show that mir-181b is a tumor suppressor that inhibits tumor growth and angiogenesis through targeting igf-1r. in summary, our results indicate that mir-181b regulates igf-1r signaling at multiple levels. 24092860_1 we demonstrated that k-ras was a functional target for let-7a to induce cell cycle arrest, apoptosis, and inhibition of cell migration and invasion in vitro. 26047700_1 compared with mir-2400- nc, mir-2400 inhibitors abolished the targeting 30 utr of myog . 26047700_2 furthermore, silencing of mir-2400 with its inhibitor could upregulate the endogenous mrna and protein levels of myog . 24676932_1 to partly clarify this dualism, the effect of low-frequency emf on the modulation of autophagy was investigated in human neuroblastoma sh-sy5y cells, which were also subsequently exposed to a-beta peptides, key players in ad. the results primarily point that lf-emf induce a significant reduction of microrna 30a expression with a concomitant increase of beclin1 transcript and its corresponding protein. 23012423_1 moreover, we found that mir-494 induced tumor necrosis factor -related apoptosis-inducing ligand resistance in non-small-cell lung cancer through the down-modulation of bim. 23125220_1 mir-144 directly target pten in npc cells. 23125220_2 the result revealed that the expression of mir-144 was up-regulated while mrna expression of pten was down-regulated in 10 npc specimens. 23125220_3 a similar inverted correlation was also observed in all 3 npc cell line , indicating mrna expression of pten could be repressed by mir-144 in npc. 23125220_4 although the level of ago2 proteins immunoprecipitated with anti-ago2 antibody was nearly the same from cne2-144 and cne2-vec lysates, the enrichment of pten transcripts significantly decreased in mir-144 attenuated cells , strongly suggesting that pten was indeed a bona fide target of mir-144 in npc cells. 23125220_5 collectively, these results proved that mir-144 promotes tumorigenicity of npc cells via directly targeting pten. 26483346_1 these findings support the notion that mir-342-3p directly targets myc-cooperating e2f1, thereby indirectly inhibiting myc activity 26476318_1 these data provided evidence that mir-1 regulated cardiac functions by directly targeting mef2a and irx5 after hbcd induction. 20489155_1 a high-throughput experimental microrna assay showed that grn is the strongest target for mir-107 in human h4 neuroglioma cells. 20489155_2 a notable mir-107 target that we found is grn. 20489155_3 together with our transfection experiments, these data indicate that mir-107 interacts with grn mrna at least partly through the 5' mirna seed and the open reading frame grn sequences underlying this interaction appear well-conserved among vertebrate species. 23083446_1 finally, a large proportion of mir-181b associated genes devoid of the corresponding mirna recognition element, were enriched with binding motifs for the e2f1 transcription factor, which is encoded by a mir-181b targetgene. 23083446_2 this demonstrates that mir-181b has the capacity to modulate e2f1 expression through it's 3'-utr, and suggests a mechanism to explain mir-181b associated changes in genes lacking a corresponding mre. 23083446_3 this suggests that mir-181b, predicted to bindto multiple mres within the 3'-utr of e2f1, is able to indirectly influence e2f1-regulated genes as a secondary consequence of e2f1's own regulation by mir-181b. 23355742_1 further analyses demonstrated that mir-22 targeted the 3- utr region of ywhaz. 23355742_2 we fused the 3- utr sequence of mouse ywhaz to a luciferase reporter gene and found significant repression of luciferase activity by mir-22, suggesting a direct effect . 23355742_4 these data demonstrate that tumor-associated mir-22 can inhibit the expression of ywhaz by binding to its 3- utr region. 26530011_1 we used luciferase reporters containing either the wild-type prdm1 3'-utr or the prdm1 3'-utr harboring a point mutation in the critical seed region of the ebv-mir-bhrf1-2 binding site . 26530011_2 these results indicate that ebv-mir-bhrf1-2 can repress expression of prdm1 by direct and specific interaction with the prdm1 3'-utr. 26530011_3 these results demonstrate that prdm1 is a target for translational repression by ebv-mir-bhrf1-2 in lcl cells. 22163007_1 western blot analyses demonstrated that expression levels of the protein phosphatase 2a catalytic and regulatory subunits, which are putative target of mir-133 and mir-1, were decreased in hf cells. 22163007_2 targeting of the pp2a catalytic alpha and -beta subunits by mir-133 was validated using a 3'-untranslated region luciferase reporter assay . 22163007_3 moreover, mir-1 and -133 overexpression was associated with reduced protein levels of the catalytic and regulatory subunits of pp2a, increased ryr2 phosphorylation and increased arrhythmic potential in hf myocytes. 19915607_1 ectopic expression of mir-145 induced extensive apoptosis in urothelial carcinoma cell lines as characterized by caspase activation, nuclear condensation and fragmentation, cellular shrinkage, and detachment. 20053927_3 we found that brd3, ubap1 and pten are potential targets of mir-141, which had been confirmed following luciferase reporter assays and western blotting. 26254780_1 rhoe was confirmed to be a direct target of mir-200b, and rhoe itself acted as a promoter of fibroblasts apoptosis. 26254780_2 this study suggests that mmc induces fibroblasts apoptosis and reduces epidural fibrosis by regulating mir-200b expression and its targeting of rhoe. the luciferase activity of the mutated rhoe 3'-utr reporter constructs demonstrated that the mir-200b binding regions were 1,584-1,591 and 1,729-1,735 in rhoe . 26254780_3 the results from the 3'-utr luciferase reporter activity and western blot analysis shown that mir-200b could directly target and inhibit rhoe expression. 22266786_1 we show that mir-1187 regulates hepatocyte apoptosis by targetin caspase-8. 26909600_1 this result further supported that mir-329 targeted to met. 26909600_2 these results suggest that mir-329 binds directly to the predicted binding site in the met 3'-utr and negatively regulates met expression. 26837280_1 notably, snail was identified as an mir-130b direct target and inversely correlated with e-cadherin expression. 26837280_2 these results suggest that mir-130b directly suppresses snail that subsequently regulates emt and fibrosis related gene expressions. 26837280_3 mir-130b targeted snail and mir-130b abrogation enhanced the expression of markers related to emt and fibrosis. 20601471_1 crfa functions to stabilize the cc3461 transcript. 20601471_2 complementarity between a region of crfa and the terminal region of the cc3461 5'-untranslated region and also the behavior of a deletion of this region and a site-specific base substitution and a 3-base deletion in the crfa complementary sequence suggest that crfa binds to a stem-loop structure upstream of the cc3461 shine-dalgarno sequence and stabilizes the transcript. 26406949_1 nrp1 was proved to be a direct target of mir-365, using luciferase assay and western blot. 26406949_2 taken together, these results indicate that nrp1 is a direct downstream target for mir-365 in mm cells. in addition, the luciferase reporter assays suggested that mir-365 targets nrp1 directly. 21709246_2 mir-23a directly bound the 3' utr of xiap, and mir-23a inhibition led to an increase in xiap mrna in vitro, demonstrating that xiap is a previously uncharacterized targetfor mir-23a. 21709246_3 use of anti-搈ir-23a to inhibit mir-23a activity partially rescued the luciferase activity by inhibiting the ability of mir-23a to bindto its targetsequence , which confirmed that mir-23a directly binds positions 2,675-2,698 of the 3'-utr of xiap. 21709246_4 enhanced mir-23a expression is likely responsible for the decreased xiap protein expression, despite elevations in xiap mrna, that was seen in sham females . 26828271_1 the results showed that mir-489-5p directly targets the gse1 through its 3'utr region. 21067538_1 in mammary epithelial cells and breast carcinoma cells, mir-10b can directly suppress the translation of hoxd10, an mrna encoding a transcriptional repressor that inhibits expression of several genes involved in cell migration and extracellular matrix remodeling, such as rhoc, urokinase plasminogen activator receptor, alpha3-integrin, and mt1-mmp 1 . 21067538_2 interestingly, hoxd10 is not only targeted by the mir-10b mirna, but also targeted by a long noncoding rna termed hotair, which has also been shown to promote breast cancer metastasis 1 . 21067538_3 ostensibly, hotair reprograms the chromatin state, causing increased polycomb repressive complex-2 occupancy on promoters of genes that inhibit breast cancer progression, including hoxd10 . 18789835_5 these facts suggest that mir-27a could specially bindto the 3'utr of prohibitin mrna and repress the gene expression. 18789835_6 these data highlight the prediction that prohibitin is a direct targetfor mir-27a. 18789835_7 as a result, when mir-27a was blocked, prohibitin mrna was subsequently elevated compared with the control group, with a 19% increase extent , indicating that mir-27a regulates endogenous prohibitin mrna levels through mechanism of mrna degradation. 21937511_1 we validated the technique using a biotin-tagged mir-122 targeting several reported target such as cat-1 , adam17 and bcl-w . 21876160_1 taken together, these results demonstrate the direct posttranscriptional repression of lrp by gcvb and offer an srna-transcription-factor regulation scheme for the control of amino acid availability. 26503985_1 therefore we carried out in vitro experiments to confirm that ncf1 , as well as cybb are indeed targets of mir-448-3p and mir-9, respectively. 26503985_2 identical experiments with a luciferase construct containing mouse 3- utr region of cybb were conducted to test if mir-9 targets this gene. 26503985_4 our results indicate that in vivo inhibition of mir-448-3p with its lna-antimir inhibitor significantly increased ncf1 expression on both, gene and protein levels. 22828209_1 furthermore, bioinformatics analyses and in vitro studies suggested that mir-302a plays a critical role in mediating the effects of folate on cell proliferation and cell cycle-specific apoptosis by targeting lats2 gene. 23244216_1 moreover, up-regulating mirna-146a in dcs effectively decreased cd40 expression by targeting traf6 and irak1. 23244216_2 we also demonstrated that transfection of mirna-146a efficiently inhibited the expression of irak1 and traf6, both in the mrna level and protein level . 23244216_3 this observation indicated that mirna-146a regulates cd40 expression by targeting irak1 and traf6. in addition, mirna-146a could directly targetthe main adaptor proteins, irak1 and traf6, to regulate cd40 expression on dcs. 21743299_2 we identified notch1 as a direct targetgene of mir-34a. 21743299_3 overexpression of mir-34a leads to a decrease of notch1 protein level in u373mg and shg44 cells , indicating the negative regulation of notch1 by mir-34a. 21743299_4 the binding was specific, because the luciferase with the mutated notch1 3'utr was not affected by mir-34a . 21743299_5 these data indicated that notch1 is a direct targetgene of mir-34a. 21743299_6 these results supported the inference that the tumor-suppressing activity of mir-34a is mediated through negative regulation of notch1. 25598954_1 according to our results, the use of mir-155 inhibitor increased the activity of caspase-3 by 2 fold in 75 nmol concentration. in this research, we found that the proper increase of mir-155 inhibitor concentration can inhibit mir-155 and consequently increase caspase-3 activity and induce apoptosis in the jurkat cells leading to cell death ultimately. 23125370_1 hypoxia-induced up-regulation of mir-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including plk1, cdc25b, cyclin f, bub1b and fam83d. 23125370_3 we found that hypoxia-induced up-regulation of mir-210 was highly correlated with the down-regulation of plk1, cdc25b, cyclin f, bub1b and fam83d genes involved in mitotic regulation. 23125370_4 mir-210 suppressed the expression of these genes by directly targeting their 3 '-untranslated regions . in contrast, inhibition of endogenous mir-210 with specific mirna inhibitor could reverse the down-regulation of plk1, bub1b, cyclin f, pds5b and cdc25b by hypoxic stress, suggesting that these genes might be mir-210 targets . 23125370_5 it was shown that over-expression of mir-210 also down-regulated the protein expression of plk1, cyclin f, bub1b, cdc25b and fam83d in both hela and cne cells in normal culture condition . 20514023_1 finally, loss of plcg1 in part mimicked the effect of mir-200bc/429 overexpression in viability, apoptosis and egf-driven cell invasion of breast cancer cells. 23211718_1 mir-150 mimics inhibited p300 3'-utr luciferase reporter activity, as well as endogenous p300 expression. in addition, mir-150 mimics prevented glucose-induced cardiomyocyte hypertrophy. 23211718_2 co-transfection with a p300 expression vector and mir-150 mimics reversed the protective effect of mir-150 on cardiomyocyte hypertrophy. 18367714_1 here we show that human mir-148 represses dna methyltransferase 3b gene expression through a region in its coding sequence. 18367714_2 this region is evolutionary conserved and present in the dnmt3b splice variants dnmt3b1, dnmt3b2, and dnmt3b4, but not in the abundantly expressed dnmt3b3. the expression of mir-148a affects the mrna stability of dnmt3b1, but not dnmt3b3, leading to a relative increase in the abundance of dnmt3b3 compared with dnmt3b1 and all other dnmt3b splice variants that express the targeted site. 18367714_4 as expected from the sequence similarity between mir-148a and mir-148b, a similar reduction of gfp-dnmt3b1 expression in cells expressing mir-148b was observed . 18367714_5 these results suggest that the presence of mir-148 represses the expression of dnmt3b1. in conclusion, we present evidence for a functional interaction of human mir-148 with the dnmt3b1 cds. it would be interesting to see whether mirna-mediated regulation of protein coding regions turn out to be a common theme in mirna targeting of mammalian mrnas or the exception that confirms the rule. 25524633_1 mir-95 depletes sumf1 protein levels and suppresses sulfatase activity, causing the disruption of proteoglycan catabolism and lysosomal function. 22426647_1 overexpression of mir-155 significantly reduced the protein levels of smad2 and repressed the activity of a luciferase reporter containing one of the two predicted mir-155 binding sites in smad2 3'-utr, indicating that smad2 may be a mir-155 target gene. 22426647_2 taken together, these data suggest that mir-155 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting smad2. 22426647_3 these data indicate that mir-155 may target smad2 gene through the 8-mer seeding region of 3'utr. 22426647_4 taken together, our data suggest that mir-155 may attenuate the expression of smad2 by directly targeting the 3'utr of smad2. 22426647_5 we showed that only the 8-mer site contributed to mir-155 repressing actions on the 3'utr of smad2; similar results were obtained in a recent study on mir-155 targeting smad2 in macrophages. 22821679_1 in addition to the known target p27 and p57, we identify aryl hydrocarbon nuclear translocator messenger rna as a novel target of mir-221, which contributes to the pro-proliferative activity of mir-221. 22821679_2 next, to investigate whether cell cycle regulators are affected by knockdown of arnt mrna, we determined the protein levels of the cdk inhibitors, p21 and p27. 26793992_1 the mirna target analysis tool mirwalk 23 was used to screen validated targets of mir-27a,mir-181a and mir-20b: hif1a was found to be a validated target of mir-20b, mdr1 a validated target of mir-27a and hipk2a gene regulated by mir-181a and mir-27a. 26793992_2 to confirm the targeting of hif1a, mdr1 and hipk2 by mir-27a, mir-181a and mir-20b, a correlation analysis was carried out. 26793992_3 a negative correlation was found between each gene hif1a, mdr1 and hipk2 and the correlated mirna. 26793992_4 the expression of the three mirna target genes hif1a, mdr1 and hipk2 was studied. 26793992_5 interestingly, an inverse trend of gene expression was highlighted compared to that of mir-27a, mir-181a and mir-20b. 26793992_6 higher median expression levels of hif1a, mdr1 and hipk2 were found in gastric n3 tumors and in males, while no difference was found in gene expression with respect to tumor size or gc patient age. 23558708_1 these data established that mir-200b binds the gata-4 3'-utr region, resulting in mrna degradation and translation repression. 22294637_1 mir-199a* is a direct regulator of cox-2 expression in oa chondrocytes. 22294637_2 these results demonstrated that mir-199a* and mir-101_3 both bindthe seed sequence present in the 3'-utr of human cox-2 mrna, but the inhibitory effect on luciferase activity was more pronounced for mir-199a*. 22294637_3 this suggests an indirect effect of mir-101_3 on the post-transcriptional regulation of cox-2 expression in oa chondrocytes. 22294637_4 these data suggest that il-1-beta-induced activation of p38-mapk negatively regulates the expression of mir-199a* which may be necessary for the unobstructed translation of cox-2 mrna and expression of cox-2 protein in human oa chondrocytes. 26384021_1 to identify the target gene of the mir-17-5p with ulk1 through the informatics software, we found the binding site as ; dual luciferase data shows that the mir-17-5p can obviously inhibit the luciferase activity of ulk1-3'-utr, but not the luciferase activity of ulk1-3'-utr mutant, ; our data shows that the mir-17-5p can obviously inhibit the expression of ulk1 protein by western-blot . 26165721_2 thus, our data demonstrate that mir-31 is capable of directly targeting a sequence within the 3'-utr of gprc5a mrna and that gprc5a is one of the key targets of mir-31 in treg-cell differentiation. 19749093_1 mll and af4 mrnas possess several putative mir-128b binding sites that are responsible for down-regulation by mir-128b. 19749093_2 to determine whether these sites allow down-regulation by mir-128b, and thus whether mir-128 can down-regulate mll and af4, as well as the chimeric mll-af4 and af4-mll mrnas, the 3'-utr regions containing these mir-128b binding sites were cloned downstream of the reporter renilla luciferase open reading frame. 19875930_1 in this study, we observed that the expression of mir-125a was inversely correlated with hur expression in several different breast carcinoma cell lines. 19875930_3 increased cytoplasmic localization of hur is a prognostic marker in breast cancer. 19875930_4 real time pcr and gene reporter assays indicated that hur was translationally repressed by mir-125a. 19875930_5 re-establishing mir-125a expression in breast cancer cells decreased hur protein level and inhibited cell growth. 19875930_8 importantly, the repression of cell proliferation and migration engendered by mir-125a was partly rescued by hur re-expression. 19875930_9 our results suggest that mir-125a may function as a tumor suppressor for breast cancer, with hur as a direct and functional target. 23890083_1 we found that apobec3g also blocks dnd1 function to restore mir-372 and mir-206 inhibition through the 3'-utrs of lats2 and cx43, respectively. 23890083_2 in summary, these experiments lead us to conclude that apobec3g is able to block dnd1 function and restore mirna-mediated translation repression. 25296715_1 in turn, zeb2 is also a direct target of mir-145. 25296715_2 taken together, our results demonstrated that zeb2 was a bona fide target of mir-145. in this study, we have found that mir-145 directly targets zeb2 and represses zeb2 expression, and in turn, zeb2 suppresses the expression of mir-145 in pca. 17911593_1 modulation of mir-155 and mir-125b levels following lipopolysaccharide/tnf-alpha stimulation and their possible roles in regulating the response to endotoxin shock. 20353999_1 we find a significant negative regulatory effect on the myo6 3'utr by both mir-143 and mir-145. 20353999_2 mutation of the potential binding sites for mir-143 and mir-145 in the myo6 3'utr resulted in a loss of responsiveness to the corresponding mirna. 20353999_3 our data indicate that mir-143 and mir-145 are involved in the regulation of myo6 expression and possibly in the development of prostate cancer. 20353999_4 myo6 is a direct target of mir-143 and mir-145. 20353999_5 these data show that the myo6 mrna is an independent targetfor both mir-145 and mir-143. 7534408_2 since the stimulation of rcsa transcription by this small rna does not depend on any sequences from within the rcsa transcript, dsra acts, either directly or indirectly, on rcsa transcription initiation. 22995297_1 in addition, pten was identified to be directly regulated by mir-1297 through western blot and luciferase reporter assay. 22995297_3 luciferase reporter assay and western blot were performed to validate the relationship between mir-1297 and pten. in the western blot analysis, the downregulation of mir-1297 could significantly upregulate pten expression compared with the control group . 22995297_4 as for the luciferase reporter assay, mir-1297 decreased luciferase activity with pten 3'utr, but had no effect on luciferase reporter with mutated mir-1297 binding elements . 25449213_4 levels of lincrna-ufc1 correlated with those of -beta-catenin in hcc tissues. in contrast, there was a negative correlation between levels of microrna 34a and lincrna-ufc1 in hcc tissues; microrna 34a reduced the stability of lincrna-ufc1. 18334534_2 overexpression of a second srna, glmy, also activates glms expression in an unknown way.the data reveal a regulatory that glmy acts indirectly in a way that depends on glmz. 18334534_3 when the intracellular glcn-6-p concentration decreases, glmy accumulates and causes in turn accumulation of full-length glmz, which finally activates glms expression. in glmz mutants, glmy has no effect on glms, whereas artificially expressed glmz can activate glms expression also in the absence of glmy. 26549165_1 impressively, overexpression of mir-296-5p showed the same phenocopy as the effect of plk1 knockdown in nsclc cells, indicating that plk1 was a major target of mir-296-5p. 26549165_2 furthermore, using western blot analysis and luciferase reporter assay, plk1 protein expression was proved to be regulated by mir-296-5p through binding to the putative binding sites in its 3'-untranslated region . 26549165_3 the above results suggested that mir-296-5p could directly target 3'-utr of plk1. 26549165_4 these results further proved that plk1 expression could be mediated by mir-296-5p through targeting its mrna 3'-utr. 23471840_2 figure 5. curcuminoids regulate the expression of zbtb10 through a mir-27a-ros-dependent suppression. 23471840_3 in addition, zbtb10 is a mir-27a mrna target and a member of the pok family of transcriptional repressors . 23471840_4 moreover, in cells transfected with pzbtb10-3'utr luciferase construct, treatment with curcuminoids increased luciferase activity directly linked to suppression of mir-27a and decreased interaction with the 3'-utr of zbtb10 ,and transfection with the zbtb10 expression vector, decreased expression of sp1, sp3, sp4, and sp-regulated gene mdr1 . 19559015_1 the results indicated that the suppression of mir-21 by mir-21 aso significantly increased both the mrna and protein level of lrrfip1 . 19559015_2 combining targetprediction bioinformatics with expression profiling, we identified lrrfip1, which was remarkably upregulated in mir-21 aso treated cells, as a candidate targetgene of mir-21. 19559015_3 these findings suggested that lrrfip1 was directly regulated by mir-21. 26864197_1 notch 1 and yy1 are confirmed targets of mir-34a . 23933602_1 exposure of esophageal cells to bile acids activates fxr and increases levels of mirs 221 and 222, reducing levels of p27kip1 and promoting degradation of cdx2 by the proteasome. 25531695_3 subsequently, mir-125a-5p silenced hdac5 post-transcriptionally in the cells treated with hdaci. 25531695_4 thus, a regulatory loop may exist in human breast cancer cells involving mir-125a-5p and hdac5 that is controlled by runx3 signaling. 25531695_5 silencing of mir-125a-5p and runx3 inhibited cancer progression and activated apoptosis, but silencing of hdac5 had a converse effect. 26654716_1 based on computational analyses revealing 3 mir-16-binding sites in the 3- utr of kcnj2 , we conducted western blot analysis and luciferase reporter gene assays to experimentally clarify whether kcnj2 is in fact a target for mir-16. 26654716_2 transfection of mir-16 into h9c2 rat ventricular cells produced marked downregulation of kir2.1 protein expression compared to sham-treated control cells . 26654716_4 kcnj2 mrna expression was also decreased by mir-16 . 26654716_7 the regulation of the kcnj2 gene by mir-16 was confirmed by a luciferase assay, which indicated that all 3 binding sites for mir-16 responded to mir-16 expression changes. 22847611_1 we also found that mir-181a negatively regulated the expression of prkcd, a pro-apoptotic protein kinase, via targeting its 3'-untranslated region , thereby inhibiting irradiation-induced apoptosis and decreasing g2/m block. 26572862_1 these data suggest that xbp1 also is a target of mir-214 in cardiomyocyte. 26046003_1 the suppression of mir-221 resulted in decreased expression of k-ras, and nf-kappab both at the mrna level and at the protein level . 26046003_2 these results suggest that inhibiting the expression of mir-221 in caf-19 cells led to the inhibition of cell migration, invasion, and the expression of its targets k-ras and nf-kappab. 23717325_1 tp53inp1 phosphorylates p53 protein at serine-46. 23717325_2 this enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53-target genes such as p21 and pig3, cell growth arrest and apoptosis upon dna damage stress. 23717325_4 deficiency in tp53inp1 expression results in increased tumorigenesis, whereas tp53inp1 expression is repressed during early stages of cancer by factors such as mir-155. 26337460_2 mir-195 can repress the migration and invasion of prostate cancer cells via regulating fra-1. 26337460_3 we found that mir-195 expression was downregulated in two prostate cancer cell lines, ectopic expression of mir-195 significantly suppressed cell migratory and invasive capacities of pc3 and du145 cells through inhibition of fra-1. 26337460_4 these findings indicated that mir-195 could be a potential tumor suppressor by directly binding to fra-1 in prostate cancer. 26337460_5 these findings indicated that mir-195 inhibited fra-1 expression through direct binding of 3'-utr of its transcript. 26337460_6 moreover, dual luciferase reporter assay confirmed that mir-195 could specifically inhibit fra-1 by binding to a critical region located on its 3'-utr. 26807169_1 it was confirmed flotillin-1 as a direct target of mir-485-5p, and up-regulation of mir-485-5p could decrease expression of flot1 in gastric cancer cells. 26807169_2 our study suggested that mir-485-5p could be a potential prognostic marker and functions as a tumor suppressor in human gastric cancer by post-transcriptionally targeting flot1. in a conclusion, our study found that mir-485-5p was identified a tumor suppressor mirna in gastric cancer cells and can negatively regulate flot1 expression in vitro and in vivo. 22020941_1 lats2 is direct target gene of rno-mir-31. 22020941_2 the online software targetscan predicts that lats2 has a mir-31 binding site in its 3'-utr. 22020941_3 the results demonstrated that lats2 is indeed a target gene protein of rno-mir-31 in vivo. 20048743_1 to explore whether mir-21 can serve as a therapeutic target for glioblastoma, we downregulated mir-21 with a specific antisense oligonucleotide and found that apoptosis was induced and cell-cycle progression was inhibited in vitro in u251 and ln229 gbm cells; xenograft tumors from antisense-treated u251 cells were suppressed in vivo. 26173586_1 targetscan 6.2 21 and pictar 22 were used to select the target of mir-18a, and interferon regulatory factor 2 , which was found to be related with cell proliferation by go analysis, was predicted as a potential target. 26173586_2 mir-18a suppressed the luciferase activity of the wt irf2 3'utr , without effect on mut irf2 3'utr in 293 t cells. 26173586_3 these results indicated that mir-18a suppressed irf2 expression post-transcriptionally. 22348345_1 e confirmation of predicted mir-10a gene target by luciferase reporter assay: arnt, gtfh1, id4, klf4, mapre1, nr4a3, rb1cc1 and tfap2c were confirmed to be mir-10a repressible by this assay. 22348345_2 reporter assay confirmed arnt, gtfh1, id4, klf4, mapre1, nr4a3, rb1cc1 and tfap2c to be mir-10a repressible genes, with further evidence of targeting specificity provided by site directed mutagenesis of the mir-10a binding site . 21278784_1 mir-221 binds the targetsite in the 3 '-utr of the cdkn1c/p57 mrna to inhibit cdkn1c/p57 expression by post-transcriptional gene silencing to promote crc occurrence and progress, therefore serving as a potential therapeutic targetfor the prevention and treatment of crc. to investigate the regulatory effect of mir-221 on cdkn1c/p57 protein expression in crc, we examined cdkn1c/p57 mrna expression in 34 crc samples by semi-quantitative rt-pcr. 26708425_1 luciferase report assay further confirmed that tgf-alpha 3'-utr is a direct target of mir-205. in this study, we provide an important insight in support of mir-205 functioning as a tumor suppressor in os via targeting tgf-alpha. 26708425_2 moreover, mir-205-transfected cells showed a dramatic decrease in cell invasion and migration, accompanied with suppressed expression of tgf-alpha, which contains a putative binding site of mir-205 in its 3'-utr confirmed by luciferase assays; and qrt-pcr and western blot results confirmed that in os cells transfection with mir-205, the expression of tgf-alpha mrna and protein were both suppressed. 26744308_1 our data also verified that bcl-2 is the target of mir-125b. 26744308_2 more importantly, we proved that mir-125b increased the chemosensitivity of osteosarcoma cell lines to cisplatin by targeting bcl-2. 26744308_3 additionally, we demonstrated that bcl-2 is a downstream target of mir-125b and negatively regulated by mir-125b binding to its 3 ' untranslated region . 26744308_4 these results suggest that mir-125b directly targets bcl-2 by binding its seed region to their 3 ' -utr in os cells. 23404117_1 taken together, these results showed clearly that oxr1 is a downstream target of mir-200b. 20724452_1 these results confirmed hsf2 as a direct target of mir-18 and identified the site of interaction in the 3'utr of hsf2 mrna. 20724452_2 interestingly, the mrna levels of hsf2 also decreased in relation to the transfected amount of mir-18 , suggesting that mir-18 is able to operate through destabilizing hsf2 mrna. 20724452_4 we therefore conclude that endogenous mir-18 is able to regulate the expression of hsf2. 20724452_5 this pattern of expression, exhibiting an inverse correlation between mir-18 and hsf2 , strongly suggests that mir-18 targets hsf2 in spermatogenesis. 20724452_6 these results clearly demonstrate that mir-18 downregulates hsf2 in spermatogenesis. 25985365_1 next we used luciferase reporter assays based on luciferase constructs harboring wt or mutated mir-200c mres sequences in the 3- utr to confirm that all four genes were direct targets of mir-200c, but not of mir-141 . 25985365_2 mir-200 targets dnajc3, which encodes an established and crucial chaperone in beta cells, and lower dnajc3 levels may partially explain the higher atf3 mrna levels detected upon mir-200 overexpression. 25985365_3 we show that mir-200 negatively regulates a conserved anti-apoptotic and stress-resistance network that includes the essential beta cell chaperone dnajc3 and the caspase inhibitor xiap. 26509963_1 in silico database and genome-wide gene expression analyses revealed that itga3 and itgb1 were direct targets of mir-223 regulation. 26509963_2 these data suggested that mir-223 bound directly to specific sites in the 3'-utrs of itga3 and itgb1 mrna. 26509963_3 these data suggested that the role of itga3 or itgb1 protein was modulated by mir-223 and the effects of migration and invasion in pca cells. 25449431_1 b-cell translocationgene 1 was identified as a new target of mir-22, which could reverse theinhibition of autophagy induced by mir-22. 18212054_1 thus, p21 is a key targetfor the cell cycle function of the mir-106b family. 18212054_2 we show that p21 is a direct target of mir-106b and that its silencing plays a key role in mir-106b-induced cell cycle phenotypes. 18212054_6 the p21 mrna 3'-utr contains two hexamers complementary to the mir-106b family seed region. 18212054_7 to test for direct effects on the p21 transcript by mir-106b micrornas, we used a luciferase reporter carrying the complete p21 mrna 3'-utr. 20698882_1 here, we investigate the expression of mir-203 and two of its targets, p63 and suppressor of cytokine signalling-3, during human skin morphogenesis. 20698882_3 as one may expect it with mirna:target pairs, p63 and socs-3 as its targets were preferentially expressed in the basal epidermal layer where mir-203 was absent . 20698882_4 to demonstrate the specificity of interaction between mir-203 and the mirna recognition motif within socs-3 3'-utr, we generated a site-specific mutation in the mir-203 binding site. 20698882_5 when the predicted mir-203 binding site in the 3'-utr of socs-3 mrna was mutated, luciferase activity was restored . 20698882_6 p63 has been shown to be directly targeted by mir-203 . in concordance, we found that p63 and mir-203 showed mutually exclusive expression pattern within the epidermis during human skin development, further supporting a role for mir-203 as a switch between proliferating basal cells and differentiating suprabasal cells. 26730339_1 the results indicated that mir-493 obviously reduced the expression of mrna and protein of rhoc but not fzd4 and igf1r. 26730339_2 mir-493 inhibited the capability of invasion of gastric cancer in vitro by targeting rhoc. 26913720_1 these results suggested that rab27b is the target of mir-193a-3p and that srr is the target of mir-193a-5p. 26913720_2 thus, mir-193a-3p and mir-193a-5p decrease the expression of rab27b and srr, respectively, by directly targeting their 3'utrs. 21618216_1 overexpression of mir-335 resulted in an upregulation of brca1 mrna expression, suggesting a functional dominance of id4 signaling. 21618216_2 in summary, our data indicate that mir-335 affects different targets in the upstream brca1-regulatory cascade with impact on key cellular functions such as proliferation and apoptosis. 20033209_1 overexpression of let-7a can inhibit the growth of lung cancer transplanted subcutaneously in nude mice by suppression of k-ras and c-myc. 20033209_2 these data provided a strong indication that let-7a significantly inhibited the expression of k-ras and c-myc in vivo. 20033209_3 our data as well as other previous studies indicated that overexpression of let-7a could suppress the expression of k-ras and c-myc, thus leading to the growth inhibition of lung cancer in vivo. in summary, our study showed that let-7a prevented the tumor growth of human lung cancer transplanted subcutaneously in nude mice by suppression of k-ras and c-myc expression. 20596961_1 furthermore, mir-181b contributed to proliferation of aml cells by targeting mlk2. 20596961_2 the results indicated that suppression of mir-181b significantly increased both the level of mlk2 mrna and protein . 22785173_1 knockdown of mir-21 resulted in significant upregulation of programmed cell death protein 4, a proapoptotic target gene of mir-21, and substantially increased tubular cell apoptosis. 26341146_1 furthermore, mir-490-3p bound directly to hmga2 mrna 3 ' utr and mediated a decrease in hmga2 mrna and protein expression. 26341146_4 these results demonstrate that hmga2 is a functional target of mir-490-3p in osteosarcoma cells. 22121083_1 taken together, our findings suggest that mir-1915 could play a role in the development of mdr in colorectal carcinoma cells at least in part by modulation of apoptosis via targeting bcl-2. 20561597_1 these data demonstrate the hwnk4 3'-utr plays an enhancer role by crosstalking with the promoter, and mir-296 suppresses hwnk4 expression through targeting on its 3'-utr in a cell-specific fashion. 20561597_2 these results verified that mir-296 regulated gene expression through binding to the specific sequence of the hwnk4 3'-utr. 20561597_3 the data suggested that the function of mir-296 was indeed characterized as cell-specific, and mir-296 could downregulate gene expression in certain cell lines. 20561597_4 that demonstrated mir-296 downregulated hwnk4 expression mainly at the translational level. 26718483_1 these finding showed that mir-340 may directly target the 3'utr of mdm2 and have an effect on the regulation of its expression. 26352279_1 we then carried out a dual-luciferase reporter assay and confirmed that in huh7 and mhcc97l cells, cdc42 was the downstream target of mir-137 . 26352279_2 moreover, we identified cdc42 as another downstream target gene of mir-137 in hcc. 26352279_3 dual-luciferase reporter and western blot assays showed that cdc42 was directly regulated by mir-137 in hcc cells. 22564856_1 further investigations demonstrate that mir-328 acts directly on the 3'utr of ptprj, resulting in reduced mrna levels. 22564856_2 in this study, we show that overexpression of microrna-328 decreases ptprj expression in hela and skbr3 cells. 22564856_3 further investigations demonstrate that mir-328 acts directly on the 3'utr of ptprj. in this study, we report that microrna-328 target the 3'utr of ptprj resulting in its decreased expression. 22564856_4 figure 3. mir-328 increases proliferation in hela cells by repressing ptprj. 22564856_5 taken together, these data indicate that mir-328 directly regulates ptprj expression mainly through interaction with the predicted mre_4 in the 3'-utr of ptprj. 23543137_1 targeting and regulation of creb1 by mir-200b. 23543137_2 all of these data suggest that mir-200b directly target creb1 expression in glioma cells. 23543137_3 taken together, the results in this work demonstrated that the transcription factor creb1 is regulated by mir-200b in glioma, thereby indirectly regulating its targetgenes. 23543137_4 in this way, we identified a novel regulatory mechanism of creb1 using mir-200b. 23543137_6 the luciferase activity assays demonstrated that mir-200b could bindto the 3'utr of creb1 mrna . 21490602_5 the finding that mir-302b and mir-372 inhibited tgfbr2 and rhoc expression. 21490602_6 follow-up experiments confirmed that the escc mirnas function in part through met by targeting at least tgfbr2 and rhoc, but also likely smad2, zeb1 and fn1 to enhance reprogramming. 22999819_1 furthermore, two binding sites for mir-125b are identified in the 3'utr of e2f2 and overexpression of mir-125b in cd133 positive gscs represses the endogenous level of e2f2 protein. 22999819_2 e2f2 is directly regulated by mir-125b. 22999819_3 mir-125b inhibits the proliferation of cd133 positive gscs mediated by direct downregulation of e2f2. 22999819_4 these results indicate that mir-125b is a regulator of e2f2 in cd133 positive gscs by binding to the two sites in the e2f2 3'-utr. 22999819_5 the results indicate that downregulation of e2f2 is closely related to the effect of mir125b on anti-proliferation. 22210895_1 ttp promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 targetgene cdc34 expression and suppresses cell growth. 22210895_2 collectively, these results indicate that ttp inhibits cdc34 expression and let-7b mediates the effect. 22210895_3 figure 2. ttp negatively regulates the expression of the let-7b targetgene cdc34. 22210895_5 these results indicate that ttp affects the expression level of let-7b and cdc34 and the cell growth through down-regulation of lin28a in pa1 cells. 26002578_1 bcl2, an antiapoptotic molecule, was identified to be a direct target of mir-449a, and the proapoptotic function of mir-449a was mainly through targeting bcl2 expression. 26071557_2 however, mir-124 cannot decrease the mrna level of nfib , which suggests that the inhibition of nfib expression by mir-124 is at the post-transcriptional level. 26071557_3 taken together, mir-124 directly targets nfib and thus inhibits mapk/erk signaling. 26071557_4 in addition, we identified nfib as a direct target of mir-124 and that the activation of wnt/-beta-catenin signaling induced mir-124 expression. 20952513_1 our observations imply that the loss of mir-26a may result in gained expression of mtdh and ezh2, which endows tumor cells with the ability to develop chemoresistance and in turn favors tumor progression. 20952513_2 these results indicate that the effect of mir-26a is due to specific and direct interaction with the putative binding sites in the 3'-utrs of mtdh and ezh2. 20952513_3 together, the above results demonstrate that mir-26a suppresses the expression of both mtdh and ezh2 by directly targeting their 3'-utr. 20952513_4 therefore, mtdh is a functional target of mir-26a for its antitumorigenic role in mcf7 cells. 25753868_1 it was found the downregulated mir-195 and upregulated hif-1alpha were present in hypoxic atdc 5 cells. 25753868_2 mir-195 negatively regulated hif-1alpha by targeting its 3'-untranslated region. 25753868_3 moreover, the founding indicated mir-195 greatly increased apoptosis and downregulated hif-1alpha mrna occurred simultaneously in hypoxic chondrocytes. 25753868_5 all this data identified the hif-1alpha might be a direct target of mir-195. 25753868_6 all these founding illustrated overexpression of mir-195 increased the apoptosis of atdc 5 cells depending on hif-1alpha on hypoxia. 25844602_1 hence, our results indicate that sfrp4, gsk3-beta, and tle1 are the bona fide targets of mir-942. 25844602_2 these results demonstated that sfrp4, gsk3-beta, and tle1 are important for mir-942-induced stem cell-like traits and indicated that wnt/-beta-catenin signalling is a functional mediator for mir-942-搃nduced function in escc cell lines. 19293287_2 ectopic expression of mir-125b by transfection of mir-125b duplex into hek-293t cells suppresses by ;60% the activity of a renilla luciferaseconstruct containing the mir-125b mres of human or zebrafishp53 at its 3' end. 19293287_4 these data indicate that the predicted mres are critical for the direct and specific binding of mir-125b to the p53 mrna. 19293287_5 the inverse correlation between mir-125b and p53 expression/activity supports our hypothesis that p53 is down-regulated by mir-125b during zebrafishembryogenesis. 26748295_1 taken together, our results suggest that mir-203, -205, - 30c2 targets runx2 and that mir-320 targets -beta- catenin at mrna and protein level. 26748295_2 hobs responded to intermittent pth stimulation by repression of hsa-mir-30c, hsa-mir-203, hsa-mir-205, and hsa-mir-320, with a concomitant increase in a target gene for these mirnas; runx2. 26748295_4 mir-30c2, mir-203 and mir-205 targeting runx2, and mir-320 targeting -beta-catenin mrna expression. 24870742_1 exosome-derived microrna-29c induces apoptosis of biu-87 cells by down regulating bcl-2 and mcl-1. 26893696_1 collectively, these data indicate that mir-497 expression is decreased and igf-1r expression is increased in hcc tissues. 26893696_2 mirna-497 overexpression may suppress cellular growth by targeting igf-1r and inhibiting activation of the pi3k/akt pathway in hcc-derived cell lines. 23809164_2 mutations in the predicted seed sequence allowed us to validate mir-142-3p interaction with the two genes showing the strongest impairment of luciferase activity, i.e., il6st and egr2. 19535919_2 among those 13 mirnas that were differentially expressed in the hbss or rapamycin-treated cells, we found in the 3'-utr of beclin 1 the consensus sequences for mir-30a, implying thatbeclin 1 is a potential target for mir-30a. 19535919_3 to verify the change of mir-30a expression following hbss or rapamycin treatment, we performed qrt-pcr analysis of the endogenous mir-30a expression. 19535919_6 using the mimic and antagomir of mir-30a, these experiments demonstrated a suppressive role for this mirna in beclin 1 expression. 26125451_1 these results indicated that mir-9-3p regulated taz expression by directly targeting its 3'utr. 26125451_2 there was an inverse correlation between mir-9-3p and taz mrna expression in hcc cell lines 21172309_1 endogenous mir-101 regulates expression of app in human cells via a specific site located within its 3'utr. 21172309_3 mir-101 significantly reduced reporter expression by greater than 40% compared to cells co-transfected with negative control mimic or app 3'-utr reporter alone, confirming that mir-101 can downregulate gene expression via elements in the app 3'-utr . 21172309_4 therefore, mir-101 regulates reporter expression specifically via site 1 in app 3'-utr. 21172309_5 thus, endogenous mir-101 in human hela cells regulates app expression specifically via site 1 in 3'-utr. 18451139_3 the fact that mir-124a was predicted to be only partially complementary to the c/ebpalpha 3- utr bindsg site strengthened our hypothesis that mir-124a might block translation of c/ebpalpha mrna rather than degrading it. 18451139_4 to validate the predicted interaction between mir-124a and c/ebpalpha, we prepared a luciferase construct by inserting the c/ebpalpha 3- utr downstream of the luciferase reporter gene in the pgl3 promoter vector. 18451139_6 relative luciferase activity was significantly decreased 24 hours after mir-124a transfection compared with transfection with the control mirna, indicating that mir-124a interferes with c/ebpalpha mrna via a direct interaction with the 3- utr . 18451139_8 after 48 h, c/ebpalpha protein decreased substantially, supporting our hypothesis that mir-124a negatively regulates c/ebpalpha 23373996_1 western blotting analysis was performed, which indicated that mir-7 directly inhibited epidermal growth factor receptor and further antagonized the downstream protein kinases including erk, akt and stat3. 23373996_2 mir-7 significantly suppressed the phosphorylation of akt, erk and stat3, as well as mmp-2, mmp-9, survivin and pcna , which suggested that mir-7 exerted its antitumor function by direct targeting egfr on the surface of glioma cells and further antagonizing egfr-mediated downstream signaling cascade . 26373393_1 further experiments of dual luciferase assays verified microrna-16 directly targeting bmi-1. 26373393_2 collectively, these findings indicate that loss of microrna-16 may favor glioma angiogenesis, on the contrary overexpression of microrna-16 in gbm cells plays a critical role in repressing endothelial function and angiogenesis by targeting bmi-1. 26373393_3 dual luciferase assays in a172 and u87 cells confirmed that mir-16 targets the bmi-1 3'-utr . in our study, we showed that mir-16 inhibited endothelial function and glioma angiogenesis through down-regulating bmi-1in glioma cells. 24949940_1 perfect matches exist between the seed regions of mir-365 and the 3'-utr of nfib, suggesting that mir-365 can directly repress nfib expression which were verified by cloning the fragments of the nfib 3'-utr regions encompassing the target sites to the downstream of the firefly luciferase gene. 24949940_2 such targeting effects were specific to mir-365 binding because the reporter activity was less affected when transfections were repeated with mutant mir-365 binding sites in the nfib 3'-utr. 24949940_3 the above results indicated that nfib is definitely one of the targets of mir-365 in both normal and cscc cells and knockdown of mir-365 could alleviate the repression and upregulate the expression of nfib. 25156638_1 mir-146a and mir-146b inhibited irak1 and traf6 expression by binding to the 3'-utr of irak1 or traf6, respectively, in the rat macrophage cell line nr8383. 25156638_2 mir-146 has two copies, mir-146a and mir-146b-5p , two regulators of the inflammatory response located at chromosomes 5 and 10, respectively. 25156638_3 these results imply that mir-146 is able to decrease the expression of irak1 and traf6 in small-for-size liver grafts by directly binding regulatory sequences in the 3'-utr. 25156638_4 in corroboration with earlier studies on mir-146a functions in innate immune cells , this study demonstrated that mir-146a/b negatively regulates the tlr4 signaling pathway by targeting irak1 and traf6 in rat macrophages. 26896308_1 dual-luciferase reporter assays showed that pdgfr--betawas a direct target of mir-9. in addition, the dual-luciferase reporter assay revealed that pdgfr--betais a direct target of mir-9. 18483236_1 mir-7 potently suppressed epidermal growth factor receptor expression, and furthermore it independently inhibited the akt pathwayvia targeting upstream regulators. 22179828_1 further studies confirmed that mir-409-3p suppressed the expression of rdx by directly binding to its 3'-untranslated region. 22179828_2 in addition, western blot analysis demonstrated that the stably expressed mir-409 significantly inhibited the endogenous protein level of rdx . 22179828_3 these results suggested that mir-409 regulates rdx expression both through induced-mrna degradation and translational repression, which was consistent with a recent report showing that the repression of mrna by mirnas was cellular-context dependent. 22179828_4 collectively, our data suggested that inhibition of rdx expression by mir-409 was, at least in part, responsible for mir-409 suppression of cell migration and invasion and, consequently, lymph node metastasis in human gc. 21725618_1 ndrg3, a member of the n-myc downstream-regulated gene family, was up-regulated in hepg2.2.15 and was identified as a targetgene of mir-122. 21725618_2 figure 2. ndrg3 is a candidate target of mir-122. 21725618_5 these data suggest that ndrg3 is one of the direct downstream target regulated by mir-122. 21725618_6 these data confirmed that ndrg3 down-regulation as a target of mir-122 significantly inhibited the proliferation of hepg2.2.15 cells. 21725618_7 thus, mir-122 plays an important role in hbv-related hcc by targeting ndrg3. 25783182_1 we have previously demonstrated that the pluripotency factor sox2 is also directly targeted via mir-140 and can regulate stem cell signaling in breast cancer cells 26663100_1 additionally, we found that mir-548d-3p downregulated the expression of tp53bp2 by directly targeting the 3'utr. 26663100_2 we also found that knockdown of tp53bp2 significantly resorted the proliferation and apoptosis regulated by mir-548d-3p inhibitor. 26663100_3 we further determined that overexpression of mir- 548d- 3p downregulated the expression of endogenous tp53bp2 on both mrna and protein level in mda-mb-231 cells . 21447552_1 hence, gata5 is a compelling mir-92 targeteduring early zebrafishdevelopment. these results suggest that gata5 is a bona fide target of mir-92. 21447552_2 consistent with this, an increase in gata5 transcript levels was observed in mir-92 morphants as compared with nics . 21447552_3 these results show that the increase or reduction of endodermal cell numbers caused by raising or lowering gata5 levels, together with the finding that increased and decreased levels of mir-92 have converse effects that can be offset by altered gata5 expression, support the idea that the mir-92-gata5 regulatory interaction is involved in allocating correct endodermal cell numbers and maintaining proper left-right patterning. 21447552_4 these results strongly support the hypothesis that mir-92 regulates endoderm formation and left-right asymmetry by controlling gata5 expression. 25676267_1 after mir-132 transfection,the expression of caspase 3 was up-regulated,whereas the expressions of p-akt and survivin were down-regulated. 25676267_3 compared with the blank control group and negative control group,the mir-132 transfection group had significantly decreased expression of survivin but increased positive expression of ki-67 and caspase 3. 21628417_1 sqstm1 was identified as the only protein from the top 20 down-regulated hits for mir-93 with a predicted recognition site for mir-17/20/93/106/519 in the 3'-utr . 21628417_3 in addition to reduced protein levels, diminished sqstm1 mrna was detected by qpcr in cells expressing mir-93 . 21628417_4 these results indicate the predicted target-site as the important determinant for mir-17/20/93/106 mediated regulation of sqstm1 expression. 21737882_1 confirming dnm2 mrna as a target for mir-133a. 22906125_1 our results confirm that trim2 is a target of mir-200a. 22906125_2 overexpression of mir-200a significantly inhibited luciferase activity in trim2 3'-utr-transfected striatal cell. 22906125_3 mutation of mir-200a binding sites in 3'-utr region of trim2 abolished this inhibitory effect. 22906125_4 trim2 is indeed a target of mir-200a.striatal 22906125_5 cells transfected with mir-200a exhibited decreased trim2 protein levels. 22906125_6 striatal cells transfected with mir-200a antisense displayed increased trim2 levels. 25803672_1 for mir941 to differentially influence cxcl12 expression depending on the cxcl12 3'-utr genotype, the expectation would be that it must be expressed in bm stroma cells, the main source of cxcl12 in bm. 21544242_1 hif-1alpha is a key downstream target of mir-21 inregulating tumor angiogenesis. 21544242_2 the results suggest that pten mediates mir-21-induced tumor angiogenesis in cam model . 21544242_3 consistent with that pten is one of the mir-21 target, mir-21 induced tumor angiogenesis. 21544242_4 these data suggest that both akt and erk1/2 are required for mir-21 in inducing angiogenesis, indicating that akt and erk1/2 pathways are two parallel downstream pathways of mir-21 for regulating hif-1alpha and vegf expression and angiogenesis. 21544242_5 these results suggest that upregulation of hif-1alpha expression is necessary for mir-21 to induce tumor angiogenesis. 21544242_6 2 mir-21 induced hif-1alpha and vegf expression through targeting pten, thus regulating akt and erk pathways. 26337822_1 as a result, significant repression of luciferase activities was observed in mcf-7 cells co-transfected with wild 3 ' utr construct and mir-137 mimic compared to mutant construct groups , suggesting that mir-137 suppressed the translational activity of ctbp1 gene by targeting the binding site in the 3 ' utr of ctbp1 mrna. 26337822_3 meanwhile, ctbp1 mrna 3 ' utr bears a binding site of mir-137, and through transfection with mir-137, the expression levels of ctbp1 mrna and protein were both suppressed. 20708014_1 both mir-144 and mir-451 directly target cugbp2 gene. 20708014_2 collectively, these data indicate that cugbp2 transcript may represent a genuine target of both mir-144 and mir-451. 26772887_1 mir-216a mimic significantly reduced the activity of cse 3'utr when compared with control transfected cells.notably, 26772887_2 mutation of mir-216a binding site inhibited mir-216amediated repression of cse 3'utr activity. 26772887_3 mir-216a mimic showed a significant reduction in cse mrna and protein levels , and production of endogenous of h2s in both dose- and time-dependent manners. 26772887_4 taken together, our results showed mir-216a regulated abca1 expression via cse/h2s/pi3k/akt pathway,loading to foam cell formation. 26772887_5 we identified a predicted a binding site for mir-216a in the 3'untranslated region of cse, but not abca1, and the sequence of mir-216a is highly conservative in different animal species. 20855588_1 these data establish a critical role for mir-33 in the regulation of abca1 expression and hdl biogenesis in vivo. 20855588_2 abca1 is a target of mir-33. 20855588_3 western blot analysis of abca1 in thp-1-rerived macrophages and hus-e/2 transfected with mir-control and mir-33, using a lentivirus vector. 20855588_4 the suppression of abca1 protein levels in response to sterol depletion was reversed by the mir-33 decoy gene , which was consistent with the notion that mir-33 mediates cholesterol-regulated posttranscriptional control of abca1 levels. 23621248_1 these results demonstrate that socs1 is a direct target of mir-19a in gastric cancer cells. 23621248_2 taken together, our findings suggest that the socs1 gene is a direct target of mir-19a, which functions as an oncogenic mirna in gastric cancer by repressing the expression of tumor suppressor socs1. 26688820_1 further study revealed that ikappabalpha was a target gene of mir-381. 26688820_2 furthermore, western blot analysis revealed that the overexpression of mir-381 obviously decreased the protein level of ikappabalpha . in comparison, the inhibition of mir-381 enhanced the expression of ikappabalpha . 26688820_3 these data suggest that ikappabalpha is a target gene of mir-381. 26688820_4 these data indicated that mir-381 enhances nf-kappab activation through targeting ikappabalpha. 26414725_1 lasp1 and tagln2 are targets of post-transcriptional repression by mir-1. 26414725_2 mir-1 binding sites in 3- untranslated region of lasp1 and tagln2 mrnas. 26414725_3 the 3'-utr of lasp1 and tagln2 mrnas are directly targeted by mir-1. 22442669_2 to better understand molecular action of mir-128 in glioma, we searched for potential targets of mir-128 by targetscan, and tested the potential targets using bioinformatic database. 22442669_3 these results indicate that p70s6k1 is a direct target of mir-128 with the specific binding site at the seed sequence. 22442669_4 the p70s6k1 protein levels were negatively correlated with mir-128 levels in glioma tissues. 26538644_1 here, we demonstrate that microrna-33 regulates abca1 and a -beta levels in the brain. 26538644_2 these results demonstrated that mir-33 directly suppresses abca1 expression by targeting its 3' utr region. 26538644_3 inaddition, our study provides the first evidence that mir-33 is an endogenous regulator of abca1 in the brain and brain-specific mir-33 antagonism may be an effective strategy to modulate a -beta levels. 23788932_1 it is suggested that the deletion of chromosome 13 leads to the silencing of mir-15a and mir-16-1 expression, which causes an increase in the synthesis of anti-apoptotic protein bcl-2 20932331_1 real-time pcr analysis showed that bcl-6, a potential targetgene of mir-339-5p, was downregulated in mda-mb-231 cells by mir-339-5p transfection. 20932331_2 our further study showed that mir-339-5p could significantly decrease tumor cell migration and invasion capacity, which associated with downregulation of bcl-6 expression in breast cancer cells. 20932331_3 our current study revealed that mir-339-5p could inhibit expression of bcl-6 mrna, which is associated with suppression of the migration and invasion of breast cancer cells. 24854846_2 recql1 is one of the predicted mir-203 targets, and we found that mir-203 downregulated the expression of recql1 at the post-transcriptional level. 26292219_1 reexpression of mir-200 in cells expressing dn-hnf-1-beta decreased the levels of pkd1 . 26292219_2 these findings indicate that hnf-1-beta controls the expression of zeb2 and pkd1 through its regulation of the mir-200 cluster. 26292219_3 overexpression of mir-200 decreases pkd1 levels in hnf-1-beta mutant cells. 26371188_1 we find that sox4 is a target of mir-132 in b cells. in this study, we uncover a novel role for mir-212/132 as a regulator of early b cell development by targeting the transcription factor sox4. in this study, we have uncovered a novel role for mir-212/132 in regulating the differentiation of prepro-b cells to pro-b cells by targeting the transcription factor sox4. 21276775_1 these predictions were tested using mirna luciferase reporter vectors, with robo2 and srgap2 evaluated as the potential target of mir-145 and mir-214, respectively. 21276775_2 the role of mir-145 in cultured primary neurons was also investigated, and the result found that mir-145 mir-145 inhibited neurite growth and down-regulated robo2 expression. 21276775_3 a significant decrease in the expression of luciferase was observed for cells co-transfected with the full-length 3'-utr of the robo2 cdna and mir-145, as well as for the full-length 3'-utr of the srgap1 cdna and mir-214 . 21276775_4 cells transfected with the full-length 3'-utr of srgap1 and mir-145 oligonucleotides also exhibited a slight decrease in luciferase expression . 21435336_1 the interaction of hsa-mir-381 and lrrc4 is involved in the pathogenesis of glioma. 21435336_2 fig. 3 overexpression of lrrc4 inhibits endogenous expression of hsa-mir-381 in u251/lrrc4-cells. 21435336_3 however, when these chimeric plasmids were transfected with or without hsamir-381 in other cell lines, no significant differences were observed, indicating that hsa-mir-381 specifically target lrrc4 in brain cancer cells. 21435336_4 as shown by qrt-pcr and immunocytochemistry, overexpression of mature hsa-mir-381 in u251/lrrc4+ cells resulted in the down-regulation of lrrc4 at the mrna transcriptional and posttranscriptional levels . 26631043_1 mir-195 directly targets cyclin d1 by binding to its 3'-utr. 26631043_2 our data indicated that cyclin d1 was a bona fide target of mir-195. 22874921_1 in particular, we find that mir-9 and mir-132 are able to repress ectopic expression of foxp2 protein by targeting its 3' untranslated region in vivo. 22874921_2 convergent repression of foxp2 3'utr by mir-9 and mir-132 in embryonic mouseneocortex: implications for radial migration of neurons. 22874921_3 we then validated in vivo one of the identified target, foxp2, and found that convergent action of mir-9 and mir-132 prevents ectopic expression of foxp2 by targeting its 3'utr. 21460851_1 to determine the target gene controlled by mir-27a, we first searched three algorithm programs to predict the targets of mir-27a. 21460851_2 to compare the binding affinity of mir-27a with these four genes-mrnas including foxo1, prohibitin, zbtb10 and fbxw7, we used a dual-luciferase reporter system to examine their luciferase activity. 21460851_4 however, the affinity of fbxw7 mrna with mir-27a is of the highest with 50% luciferase activity suppression compared with nc treatment, while other three showed 30-37% activity suppression. 21460851_5 these observations indicate that fbxw7 is also an important target of mir-27a. 21460851_6 the results showed that the level of fbxw7 mrna in hbelh cells transfected with 200 nm mir-27a mimic was decreased by 60% compared with mimic nc measured by quantitative rt-揚cr, indicating that mir-27a regulates fbxw7 expression by mrna degradation . 21460851_7 thus, we further confirm that fbxw7 is one of the targets of mir-27a. 22406815_1 mir-217 is involved in tat-induced hiv-1 long terminal repeat transactivation by down-regulation of sirt1. in addition, mir-217 significantly inhibited sirt1 protein expression by acting on the 3'-utr of the sirt1 mrna. in addition, mir-217 significantly inhibited sirt1 protein expression by acting on the 3'-utr of the sirt1 mrna. 22406815_2 taken together, these data suggest that mir-217 reduces the efficiency of sirt1 mrna translation, rather than the abundance of the sirt1 mrna, by acting on a response element located in the sirt1 3'-utr. 22406815_3 we performed in silico studies to predict downstream target of mir-217 and used functional assays to confirm that mir-217 downregulated sirt1 by directly acting on the sirt1 mrna. 26818545_1 these results suggested that mir-26a might regulate ccnd2 and ccne2 expression by directly binding target sites in the 3- utr. 26818545_2 ccnd2 and ccne2 are direct target genes of mir-26a. 26818545_3 luciferase activity assays of wild-type and mutant ccne2 3- utr luciferase reporters after co-transfection with mir-26a mimics or normal control; c: luciferase activity assays of wildtype and mutant ccne1 3- utr luciferase reporters after cotransfection with mir-26a mimics or normal control. 25738314_1 mir- 125b directly targets podxl. 25738314_2 these results confirmed that mir-125b directly targeted podxl and regulated its expression at the transcriptional level. 26893657_1 previous studies have demonstrated that erbb2 is a target gene of mir-375 , that the pi3k/akt signal pathway is associated with erbb2 regulation, and that the activation of the erbb2/pi3k/akt signal pathway may promote drug resistance ; however, to the best of our knowledge, whether mir-375 alters the sensitivity of gastric cancer cells to ddp via regulation of the erbb2/pi3k/akt pathway is unknown. 26893657_2 western blotting demonstrated that upregulation of mir-375 expression levels in the sgc7901/ddp cells markedly decreased the protein expression levels of erbb2 and p-akt, as compared with the mir-control and sgc7901/ddp parental cells . 26893657_3 these results suggest that overexpression of mir-375 may sensitize sgc7901/ddp cells to the effects of ddp via inactivation of the erbb2/pi3k/akt pathway. 21187093_2 although the pten 3' utr is not a perfect match to the seed sequence of mir-21 because there was a g:u pair , a previous study showed that pten is a mir-21 targetin cholangiocarcinoma cell lines . 21187093_3 we thus hypothesized that pten is a direct mir-21 targetin k562 cells. 21187093_4 these results show that pten is a target of mir-21, and that overexpression of mir-21 activates the pi3k/akt pathway by decreasing the pten protein level. 25582055_1 among the validated mir-21 target genes, pdcd4 plays an important role in cancer cell migration . in our previous study, we showed that adar2 inhibits glioblastoma cell migration . 25582055_2 here, we demonstrate that the expression of adar2 in glioblastoma cells can significantly down-modulate mir-21 and up-regulate pdcd4 protein levels in the u118 and a172 cell lines. 25342468_1 transformer 2-beta and mir-204 regulate apoptosis through competitive binding to 3' utr of bcl2 mrna. 20956944_1 the 3' -untranslated region of integrin--beta8 harbors a typical targetsequence for mir-93 . 20956944_2 targeting of integrin--beta8 by mir-93 expression. 20956944_4 to test whether or not integrin-b8 expression was correlated with mir-93 levels, a number of human cell lines were analyzed for integrin-b8 expression by western blotting and mir-93 levels were analyzed by real-time pcr . 20345657_1 overexpression of mica resulted in a 3-fold decrease in the b-galactosidase activity compared with the vector control,whereas overexpression of rybb had no noticeable effect on the expression of the ompt-lacz fusion. 26297545_1 based on conserved sequences in 3 ' utr for mir-99b binding, we identified the insulin-like growth factor-1 receptor gene as a direct target for mir-99b. 26297545_2 our results demonstrate that mir-99b is decreased in ca samples compared to that in normal skin, and mir-99b plays a role in cell proliferation by targeting igf-1r, which regulates the pi3k/akt signaling pathway. 26297545_3 such significant decrease in reporter activity was not seen when the reporter was in the vector containing the mutant igf-1r 3 ' -utr , in spite of the presence of mi-r99b, indicating that sequences in the 5602- 5607 bp region of the igf-1r 3 ' -utr indeed interact with mir-99b, inhibiting expression of igf-1r. 26134491_1 egfr was selected from several putative mir-133a target genes, since igf-1r has been shown to be involved in tumorigenesis and metastasis . 26134491_3 5a, mir-133a contains two predicted binding sites in the 3'utr of egfr mrna. 26134491_5 to determine whether mir-133a affects the regulation of endogenous efgr, we transiently reintroduced the mir-133a mimic into hela cells. 26134491_6 we found that ectopic expression of mir-133a markedly reduced egfr protein expression in the hela cells , suggesting that egfr is a bona fide target of mir-133a. 26420324_1 mir-182 was negatively correlated with rac1 by person analysis . 26420324_2 downregulation of mir-182 and upregulation of rac1, -beta-mhc, alpha-sma were found in high glucose-induced cardiomyocyte. 26420324_3 after transfection of mir-182 mimics, hypertrophic changes were significantly reduced and rac1 as well -beta-mhc expression was significantly downregulated in cardiomyocyte incubated with high glucose. 26420324_4 microrna-182 modulates high glucose-induced cardiomyocyte hypertrophy via targeting rac1. 22996741_1 furthermore, dual-transfection of a549 cells with mir-155 sirna and apaf-1 sirna resulted in the attenuation of apoptosis and dna damage. 22996741_2 the results showed that expression of mir-155 was significantly higher in lung cancer tissues than in paracancerous and normal tissues; whereas apaf-1 expression was lower in the lung cancerous tissues. 26309499_1 zdhhc2 was identified as a direct target of mir-155 and downregulation of zdhhc2 prompted cell migration in npc. 26309499_2 collectively, inhibition of mir-155 suppresses cell migration in npc through targeting zdhhc2. 26309499_4 in our study, we found that mir-155 inhibitor could increase endogenous zdhhc2 protein expression in npc cne1 and tw03 cells, and luciferase reporter assay was performed to identify zdhhc2 as direct targets of mir-155. 26318298_1 we observed that mir-335 has a putative binding site in the 3'-utr of birc5. in both hek 293 t and sgc-7901 cells,mir-335 could only significantly weaken the relative luciferase activity of the reporter carrying wide-type sequences, but not the mutant construct. 22294552_1 downregulation of tumor suppressive mir-1285, which target oncogenic genes including tgm2, might contribute to rcc development. 22294552_3 furthermore, both tgm2 mrna and tgm2 protein expression levels were markedly downregulated in mir-1285 transfectants in comparison with the control transfectants . 22294552_4 our data indicated that upregulation of oncogenic tgm2 may be due to downregulation of tumor suppressive mir-1285 in human rcc progression. 22294552_5 figure 3 mir-1285 directly regulates tgm2 in rcc cells. 22833211_1 fluoxetine, acting on serotonergic raphe neurons, decreases the amount of mir-16 in the hippocampus, which in turn increases the levels of the serotonin transporter , the target of sri, and that of bcl-2 and the number of cells positive for doublecortin, a marker of neuronal maturation. 22833211_3 neutralization of endogenous mir-16 by direct injection of anti-mir-16 in the hippocampus increased the levels of sert and bcl-2 and the number of dcx-positive cells, similarly to fluoxetine injection in the raphe . 22071331_2 similarly, transfection of mir-125b inhibitor into hbecs increased 4e-bp1 protein expression . 22071331_3 however, no significant change of 4e-bp1 mrna level was found after transfection of mir-125b mimic or inhibitor , suggesting that mir-125b can interfere with 4e-bp1 mrna translation but not degradation. 22071331_4 taken together, these results verified that 4e-bp1 mrna is a direct target of mir-125b. 22071331_5 however, knockdown of 4e-bp1 gene with sirna could abolish the effect of mir-125b on the further induction of ifn-alpha/-beta in beas-2b cells, which indicates that the effect of mir-125b was specifically caused by targeting of 4e-bp1 mrna. 22071331_6 the 4e-bp1 protein expression levels inversely correlated with mir-125 levels in sinonasal mucosa . 25693145_1 at the same time, we also confirmed that stmn1 and cox2are the other targets of mir-102 in hcc 25683915_1 transient transfection of mir-34c to either vsmcs or a10 cells inhibited cell survival by inducing apoptosis, which was accompanied by an increase in expression of p21, p27, and bax. 21249429_1 vegfa and pik3r2 were confirmed as the target of mir-126 by luciferase reporter assay and western blot. 21249429_2 moreover, introduction of mir-126 mimics into mcf-7 could effectively down-regulate pik3r2 and vegfa expression and decrease the akt phosphorylation level . in conclusion, endothelial-specific mir-126 was excised from egfl7 pre-mrna without affecting splicing and expression of its host gene, and could targetboth vegfa and pik3r2. 21602190_2 we found a significant decrease in the expression level of mir-101a , and a significant increase in that of cox-2 both at the mrna and protein levels. 21602190_3 the expression levels of ezh2 and cfos, other targets of mir-101a , were not significantly altered at the mrna level but substantially increased at the protein level . 21602190_4 the increase in the protein amount without a significant change in the rna amount indicated that ezh2 and cfos were regulated post-transcriptionally in the liver of the mice. 25263437_1 to furthermore determine whether extracellular timp-1 is sufficient to induce mir-210 upregulation, we incubated a549l with recombinant timp-1 in a concentration similar to timp-1 levels in lung cancer patients 13 or with medium conditioned by timp-1 overexpressing cells. 25263437_2 we found significant upregulation of mature mir-210 as well as pri-mir-210 upon extracellular timp-1 stimulation which suggests a paracrine mode-of-action by which timp-1 can induce mir-210 in a549l adenocarcinoma cells. 25263437_3 we could also verify the underlying concept as a knockdown of timp-1 led to a reduction of pri-mir-210 and mir-210 in a human ovarian carcinoma cell line as well as a decrease of primir-210 in a549l lung adenocarcinoma cells. 25263437_4 we could show that timp-1-induced increase of mir-210 levels were sufficient to trigger its regulative role and to decrease mir-210 targets. 22568714_3 inhibits hcmv ie1 gene expression, and acts as an immune response inhibitor to help viral replication.inhibits 22568714_4 hcmv ie1gene expression, and acts as an immune response inhibitor to help viral replication specifically downregulates micb expression during viral infection, leading to decreased binding of nkg2d and reduced killing by nk cells. 19672202_2 the downstream targets of hsa-mir-21, pten and programmed cell death 4, were found to be greatly reduced in 3 of 4 cholesteatoma samples. 19672202_5 this study specifically identified up-regulation of hsa-mir-21 concurrent with down-regulation of potent tumor suppressor proteins pten and programmed cell death 4. these proteins control aspects of apoptosis, proliferation, invasion, and migration. 18832181_2 a significantly negative effect on luciferase activity was observed in the presence of mir-126 on the 3 utr of plk2. 18832181_3 these results indicate that plk2 is a bona fide target of mir-126. 23300839_1 using mirna target-detecting software, we analyze the mrna sequence of ngal and identify a target site for microrna-138 in nucleotides 25-53 of the 3' utr. 23300839_2 this finding led to our investigation of the role of mir-138, a multi-functional molecular regulator which may regulate ngal expression and thereby play a role in ngal-induced tumorigenesis. the results suggested that the ngal gene was a target of mir-138, which down-regulated ngal protein expression via post-translational modification. 24285464_1 mir-141 inhibits tm4sf1 protein expression. 24285464_3 these results suggest that mir-141 directly targets tm4sf1 via the binding site in its 3'-utr region. 26064322_1 these results indicate that the expression levels of mir-143 are decreased in patients with ds. the expression of mir-143 may be related to the increase expression of cox-2. 24871856_4 transfection of mir-182 into muscle cells decreased foxo3 mrna 30% and foxo3 protein 67% and also prevented a glucocorticoid-induced upregulation of multiple foxo3 gene targets including mafbx/atrogin-1, autophagy-related protein 12 , cathepsin l, and microtubule-associated protein light chain 3 . 26744864_1 moreover, mir-26b was found to negatively regulate cox-2 protein level by directly targeting its 3'-utr. 26744864_2 in addition, we found cox-2 is a potential target of mir-26b. 26744864_3 these results suggest that mir-26b can specifically bind to the 3'-utr of cox-2. 26744864_4 taken together, these results indicate cox-2 is a direct downstream target of mir-26b in lung cancer cells. 23139153_1 direct interaction between mir-197 and p120 catenin mrna sequence was confirmed by 3'utr assay, and knockdown of p120 catenin recapitulated emt induction in pancreatic cancer cells. 23139153_2 the 3' utr sequence of p120 catenin mrna contained seed sequence which possibly interact with mir-197 . 23139153_3 based on these results, we concluded that p120 catenin is a direct target of mir-197. 23139153_4 these results indicate that attenuated expression of p120 catenin in ida could be explained by increased mir-197 expression to certain extent. 20347499_1 over-expression of let-7c or let-7g led to a clear decrease of bcl-xl expression in huh7 and hepg2 cel lines. 20347499_2 reporter assays revealed direct post-transcriptional regulation involving let-7c or let-7g and the 30-untranslated region of bcl-xl mrna. 20347499_3 let-7c and let-7g downregulate bcl-xl expression by directly targeting the 3'utr of bcl-xl mrna. in conclusion, we have demonstrated that let-7 mirna negatively regulates bcl-xl expression in hccs. 20347499_4 a single base mutation prevented the downregulation of firefly luciferase induced by let-7c or let-7g, which strongly suggests a direct inhibitory effect of let-7 on bcl-xl expression . 20347499_5 these results are consistent with the hypothesis that let-7 mirnas negatively regulate bcl-xl expression independent of transcriptional regulation. 26462018_1 sufu is a direct target of mir-214 in lad cells. 26462018_2 mir-214 promotes lad metastasis by directly targeting sufu. 26462018_3 sufu was a direct functional target of mir-214 in lad metastasis. 26107945_1 mir-133a sensitized doxorubicin response in doxorubicin-resistant breast cancer cell sub-line mcf-7/dox via its direct regulation of ucp-2 expression. 26663205_2 furthermore, rip verified the interaction between hnrnpa2b1 and lnc-hc in vivo, and surprisingly hnrnpa2b1 also directly bound to cyp7a1 and abca1 mrnas . 26663205_3 rip assay showed that lnc-hc-nucleoprotein complex could bind to the cyp7a1 and abca1 mrnas, whereas lnc-hc did not bind to target mrnas in the absence of nucleoproteins . 26663205_4 lnc-hc increased the expression of hnrnpa2b1 in nucleus and they formed an rna-protein complex, which further bound to the target mrnas, cyp7a1 and abca1. 25766529_1 it is noteworthy that dnmt3a/3b expression levels exhibited an inverse correlation with mir29b, which suggested that these molecules are targets of mir29b and are negatively regulated by mir29b in mouse early embryos. 25672252_2 we showed that the mir-16 overexpression reduces cyclin d1 and bcl2 at messenger rna and protein levels in mcf-7 cell line. 25997961_3 furthermore, alk was identified as a target of mir-1271, alk overexpression remarkably attenuated the tumor suppressive effects of mir-1271 on oscc cells. 25997961_4 our findings indicate that mir-1271 acts as tumor suppressor in oscc and might be used as an therapeutic target for the development of treatment for oscc. 21098294_1 we identify mir-130/301, which are dramatically up-regulated following t-cellactivation, as able to down-regulate cd69 expression via binding to a conserved site in the 3'utr of cd69 mrna. 21098294_2 there are four members of the mir-130/301 family in the mouse genome: mir-130a, mir-130b, mir-301a, and mir-301b . 21098294_4 6c, mir-130b and mir-301a slightly but consistently down-regulated cd69 expression in dicer / cd8+ t cells compared with scrambled oligo controls. 21098294_5 moreover, combining mir-130b and mir-301a oligos resulted in a more substantial down-regulation of cd69 expression in dicer / cd8+ t cells. 21098294_6 taken together, these data suggest that mir-130/301 expression are dramatically enhanced after t-cell activation and down-regulate cd69 expression in cd8+ t cells. 22964638_3 we demonstrate that mir-30b/c and mir-21 target respectively the 3' untranslated region of caspase-3 and tap63 mrnas, and that those proteins mediate some of the effects of mir-30 and -21 on trail resistance, even in human glioblastoma primary cells and in lung cancer cells. 26647742_1 programmed cell death 10 is the direct target of mir-425-5p which is required for the regulatory role of mir-425-5p in chemoresistance. 26647742_2 we provided evidence that mir-425-5p can directly modulate chemoresistance in these cells by regulating the expression level of its downstream target pdcd10 both in vitro and in vivo. 26647742_3 as shown in figure 4e, cotransfection of mir-425-5p precursor with wild-type pdcd103 0 -utr reporter construct significantly repressed relative luciferase activity, whereas mutation of the mir-425-5p-binding site eliminated this effect, supporting that pdcd10 is a direct target of mir-425-5p in crc cells. 26647742_4 using bioinformatics method, combined with experimental approaches, we identified pdcd10 as the directly target of mir-425-5p as demonstrated by both western blot analysis as well as luciferase assay . 22445466_1 these results suggest that catalase and stathmin are likely to be direct targets of mir-7 in cho cells, though further work would need to be carried out to confirm this. 20577838_1 direct interaction between mir146a and its predictive targetgene smad4 were confirmed by luciferase assay. 20577838_2 down-regulation of mir-146a and upregulation of smad4 at protein levels were demonstrated. 20577838_3 these data suggested that mir-146a might influence proliferation of apl cells through tgf-beta1/smad signal transduction pathway during atra induction. 23437250_1 looking for the effectors of these antineoplastic functions, we identified adam9 and mmp7, two metalloproteases playing a pivotal role in melanoma progression, as direct targets of mir-126&126*. 23437250_2 mir-126&126* play their tumor suppression function through the direct inhibition of adam9 and mmp7, in turn impairing the activation of their common target heparin-binding egf-like growth factor . as shown , co-transfection experiments with the wildtype 39utr regions of adam9 and mmp7 showed a significant inhibition of the luciferase activity, thus confirming the direct targeting of mir-126&126*. 23437250_3 in this report, we demonstrated that adam9 and mmp7 were direct targets of mir-126&mir-126*, whereas they only indirectly regulated opn , possibly through an auto-sustaining loop linking opn and mmp7 . 22289118_1 mcas could base-pair with the flhd 5'-utr in two regions, relieving the secondary structure around the ribosome binding site, resulting in increased translation of the flhd and flhc proteins. 26893786_1 at the molecular level, the results showed that glycogen synthase kinase-3 -beta was identified as a target of mir- 26a, and the ectopic expression of mir-26a inhibited gsk-3 -beta by directly binding to the 3'-utr. 26893786_2 mir- 26a downregulates gsk- 3 -beta through binding to the 3'utr of gsk- 3 -beta mrna. 26893786_3 additionally, gsk-3 -beta was indicated to be a target of mir-26a, and mir-26a expression was negatively correlated with gsk-3 -beta expression in the os tissues. 17957144_1 ovarian cancer patients with high hmga2 and low let-7 expression in their cancer cells had a lower survival than patients with a low hmga2/high let-7 ratio. 17957144_2 hmga2 upregulation occurs early during oc progression before the tumors begin to metastasize both in human patients and in an oc mouse model.hmga2 is a more sensitive target of let-7 than ras. 22484852_2 mir-22 exhibited excellent anti-lung cancer activity in vitro and in vivo, and post-transcriptional regulation of erbb3 might be a potential mechanism. 22484852_3 all these results indicated that mir-22 exert inhibitory effects on erbb3 expression via interaction with the 3'-utr of erbb3. 22484852_4 additionally, over-expression of erbb3 in a549 and h1299 cells significantly prevents the inhibitory effects of mir-22 on proliferation and invasion. 26576679_1 the cell cycle regulator ccnd1, and ras-mapk pathway components grb2, erk2 and rsk2 were directly repressed by mir-634 overexpression. 26576679_2 we show that mir-634 regulates cyclin d1 and several ras-mapk pathway components , which may contribute to the effects of mir-634 on ovarian cancer cell survival and chemotherapy response. 26576679_3 as expected, mir-634 could inhibit the 3'-utr of ccnd1 and grb2, the erk2 3'-utr and the rsk2 3'-utr . in addition, we observed that mir-634 overexpression in ovarian cancer cell lines and patient samples negatively regulates important cell-cycle genes and ras-mapk pathway components . 25055044_1 our previous study has identified jak2 as a downstream target of mir-375 . 25055044_3 mir-375 may inhibit the migration and invasion of gastric cancer cells partially by targeting jak2. 25055044_4 we further determined that jak2 overexpression has no effect on the expression level of mir-375 as shown in figure s3. 20036862_1 thus, our results indicate that mir-124 regulates the expression of hes-1 at the post-transcriptional level and is involved in the retinoic acid-induced neuronal differentiation of p19 cells. 20036862_2 these results suggest that the expression of mir-124 might be associated with the differentiation of p19 cells. in addition, it is possible that a relationship exists between mir-124 and hes-1. in contrast, the level of hes-1 protein increased in the presence of lna-mir-124 ; however, the level of hes-1 mrna was unchanged . 20036862_3 these results strengthen our hypothesis that mir-124 regulates the expression of hes-1. 14685240_1 lsy-6 exerts its effects on asel through repression of cog-1. 24305048_1 here we show that hmga2 promotes lung cancer progression in mouse and human cells by operating as a competing endogenous rna for the let-7 microrna family. 24305048_2 hmga2 can promote the transformation of lung cancer cells independent of protein-coding function but dependent upon the presence of let-7 sites; this occurs without changes in the levels of let-7 isoforms, suggesting that hmga2 affects let-7 activity by altering mirna targeting. 24305048_7 taken together, these results suggest that the hmga2 transcript functions in a largely protein coding-independent but let-7 site-dependent manner to promote lung cancer cell transformation in vitro. 24305048_8 thus, these results demonstrate hmga2, via its let-7 binding sites, displaces tgfbr3 from mirna-mediated repression by risc. in total, these results suggest the hmga2 cerna directly functions by blocking recruitment of tgfbr3 to the ago2-based mirna repression complex. 21690566_1 mir-145 delivery reduced tumor proliferation and increased apoptosis, with concomitant repression of c-myc and erk5 as novel regulatory target of mir-145. 22457788_2 mir-34a and c-met are inversely expressed in human hcc tissues. 22457788_3 western blot results showed that overexpression of mir-34a and knockdown of c-met by sirna resulted in a significant decrease of endogenous c-met protein levels compared to mock or nc transfection in hepg2 cells . 22457788_5 the results showed that overexpression of mir-34a in hepg2 cells led to a corresponding decrease of endogenous c-met mrna . 26325180_2 these results demonstrated mir-206 inhibited c-met and bcl2 expression in a549 cells, and loss of mir-206 would be attributed to the over-expression of c-met and bcl2 in lung cancer cells, which were the risks of nscls. 26325180_3 second, mir-206 can directly regulate mrna expression by targeting the 3'-utr of met and bcl2, and inhibit protein expression of cyclin d1 and gene expression of cyclin d1, cyclin d2 and matrix metalloproteinase 9 , while increased p57 gene expression in lung cancer cell . 19342367_3 using frozen tumor tissues from 10 additional patients who had advanced ea, we evaluated the correlation of mir-196a with its in silico-predicted targets, keratin 5 , small proline-rich protein 2c , and s100 calcium-binding protein a9 , which are down-regulated during be progression. 19342367_5 we confirmed that mir-196a specifically targets krt5, sprr2c, and s100a9 3' utrs using mir-196a-mimic and luciferase reporter-based assays. in conclusion, this study identified mir-196a as a potential marker of progression of be and krt5, sprr2c, and s100a9 as its targets. 21502407_1 klhl12, rock2, tal1, cmpk1, snai2, and snai1 are regulated by ncrna-a2 through ncrna-a7, respectively. 21502407_2 knockdown of ncrna-a7 in a549 cells represses the expression of snai1 specifically and diminishes cell migration to levels similar to that seen when knocking down snai1. 21502407_3 ncrna-a7 serves as a transcriptional enhancer of snai1. 24608427_3 furthermore, gli3 silencing recapitulated the effects of mir-506, and reintroduction of gli3 abrogated mir-506-induced cell growth arrest and apoptosis. 26821827_1 downregulated mir-10a could accelerate ikappab degradation and nf-kappab activation by targeting irak4, tak1 and btrc. 26821827_2 collectively, these findings indicated that irak4, tak1 and btrc are specifically regulated by mir-10a in ra fls cells, and tnf-alpha and il-1-beta regulate these molecules at least partly via repressing mir-10a. 26171727_1 further investigation demonstrated that mir-214 downregulated a2ar expression by directly targeting the 3'-untranslated region of a2ar mrna. 26171727_2 these observations demonstrated that mir-214 inhibits a2ar translation and directly interacts with 3'-utr of a2ar mrna. 23352645_1 these results strongly suggest that mir-503 down-re gulates the expression of fgf2 by directly targeting its 3'-utr. 23352645_2 these results indicate that mir-503 down-re gulates the expression of vegfa through binding to its 3'-utr. 23352645_3 taken together, these results indicate that mir-503 down-regulates fgf2 and vegfa expression at both mrna and protein levels by directly targeting to their 3'-utrs. 23352645_4 these data indicated that the reduced tumor angiogenesis capacity for the mir-503 transfected tumor cells at least partially due to mir-503-med iated downregulation of fgf2 and vegfa. 23352645_5 together, these results suggest that mir-503 significantly inhibits tumor growth and angiogen esis in vivo by down-regul ating fgf2 and vegfa expression. 22942717_1 this study demonstrates that mir-338-3p inhibits proliferation by regulating cyclind1, and hbx down-regulates mir-338-3p in hcc. 19559772_1 these results suggest that lust is a novel, functional, non-coding rna that plays a role in determining the apoptotic fate of a cell by regulating the expression of rbm5 splice variants. 22134529_1 our data demonstrate that neuropilin 1 is a direct target of mir-320a and that mir-320a-mediated suppres- sion of nrp-1 is dependent upon the nrp-1 3'utr. 22134529_2 these data support the idea that nrp-1 is a direct target of mir-320a. 22134529_3 real-time pcr analysis indicated that the expression of nrp-1 in lovo cells transfected with mir-320a was downregulated compared to those cells transfected with control constructs . 22134529_6 our study demonstrates that mir-320a may suppress the invasion and metastasis of crc by directly binding to the 3'utr of nrp-1. 26304544_1 regulation of the dmpk gene by mir-206 and mir-148a. 23633075_3 we identified sp1 protein as a target of mir-711 using luciferase assay and western blot analysis . 23633075_4 sp1 protein is negatively regulated by mir-711 in cardiac fibroblasts, and its mrna expression is not altered by mir-711 . 18619465_1 the findings in this study show that cyar transcription is dependent on the camp-crp complex and that cyar rna plays a major role in carbon catabolite regulation of ompx expression.the 18619465_2 conservation of cyar and the ompx shine dalgarno region suggests that cyar rna acts as a posttranslation regulator of ompx expression by an antisense mechanism in many enterobacteriaceae. 26077733_3 moreover, partial mutation of the perfectly complementary sites in the 3'-utr of smad4 abolished the suppressive effect due to the disruption of the interaction between mir-34a and smad4 . 26077733_4 these data suggest that smad4 expression was primarily inhibited by mir-34a at the translational level. 26077733_5 together, these results confirmed that smad4 is a direct target of mir-34a and is regulated by mir-34a in cc cell lines. 22098779_1 we demonstrated that mir145 negatively regulates gbm tumorigenesis by targeting oct4 and sox2 in gbm-cd133 . 22098779_2 taken together, our data indicated that the downregulation of mir145 is accompanied by an upregulation of sox2 and oct4 in gbm-associated cscs and high-grade gbms, in which mir145 and these stemness factors may play pivotal roles in mediating gbm malignancy. 22098779_3 fig. 4. mir145 mediated the downregulation of oct4 and sox2 by directly targeting the oct4 and sox2 3' utrs. 22098779_4 the results indicated that mir145 mediated the downregulation of oct4 and sox2 by directly targeting the oct4 and sox2 3' utrs . 22098779_5 these results validated the signal transduction of mir145 and it downstream target sox2 and oct4 in gbm and gbm-associated cscs. 25903473_1 fih1 therefore may represent a very attractive common target for mir-31 and -148a implicated in gmb. the mir-148a-mediated modulation was abolished by a mutation within the binding site 1, indicating that mir-148a directly binds and represses fih1 expression . 25903473_2 altogether, these data indicate that high levels of mir-31 or mir-148a promote glioma growth by down-regulation of fih1 and thereby enhancing hif1alpha and notch pathway activity, tumor angiogenesis, and tumor progenitor expansion even in the normoxic conditions . 23221637_1 in mice, knockdown of mir-192 led to up-regulation of atp1b1 protein. 23221637_2 interestingly, mir-192 appeared to target atp1b1 through the 5'-, rather than 3'-untranslated region. 23221637_3 mir-192 regulates atp1b1 expression and na + /k + - atpase activity in human kidney cells. 23221637_4 overall, these results suggested mir-192 interaction with atp1b1 5'-utr as the possible mechanism by which mir-192 reduces atp1b1 abundance. 23221637_5 we also showed that mir-192 interacted with atp1b1 in an unconventional manner involving the 5'-utr. 26239140_1 based on the above analysis, it was suggested that mir-19a induced nf-kappab activation, predominantly by targeting ikappabalpha, in the human gastric carcinoma cells. 21399894_1 modulation of mir-34a expression was correlated with bcl-2 and cyclin d1 protein expression changes and a direct interaction of mir-34a with bcl-2 was shown by luciferase assay. 21399894_3 by reducing luciferase activity, this shows that mir-34a directly interacts with the 3' utr region of the bcl-2 gene. 21399894_4 fig. 3 mir-34a regulates bcl-2 and cyclin d1 in mcf-7 breast cancer cells. 26774733_1 to further investigate whether mir-320 regulates mmp-13 expression during chondrogenesis, we inhibited or overexpressed mir-320 in atdc5 cells. 26774733_2 the mir-320 inhibitor induced a significant increase in the expression of mmp-13 and an obvious decrease in the expression of col2a1. 26774733_3 an opposing expression pattern between col10a1 and mir-320 was not detected when mir-320 was inhibited or overexpressed in atdc5 . 26774733_4 these results demonstrated that mir-320 reduced luciferase activity by binding to the 3'-utr of mmp-13, and that mmp-13 is a target for mir-320-mediated repression. 25912304_1 rock1 and rock2, both containing a mir-144-binding site in the 3'-utrs ,5a, were selected for further experimental validation, in view of their critical roles in tumor cell proliferation and invasion . 25912304_2 we further examined whether rock1 and rock2 levels are negatively regulated by mir-144 in os cell lines. 25912304_3 we also confirmed elevated mir-144 with reduced rock1 and rock2 protein in mir-144-overexpressing tumors of nude mice. 25912304_4 we conclude that rock1 and rock2 are direct downstream targets of mir-144 in os cells. 26347321_1 significantly, foxa1 was identified as a direct target of mir-212 in hcc. 26347321_3 thus, our data strongly suggest that foxa1 is a target of mir-212 in hcc. in sum, these data indicate that mir-212 suppresses hcc cell proliferation and induces apoptosis by inhibiting foxa1. 26347321_4 herein, we validated foxa1 as a direct functional target of mir-212 in hcc. 20682795_1 lsd1 is a direct target of mir-137. in addition, we have successfully validated lsd1, a key element of the epigenetic machinery, as one of the target of mir-137.we next explored the functional interaction between mir-137 and lsd1 . 20682795_2 the expression levels of mir-137 and lsd1 mrna were determined in six crc cell lines by taqman rt-pcr and rt-pcr, respectively . in crc cell lines with lower endogenous mir-137 expression , a higher lsd1 expression level was observed, whereas in the ht29 cell line, which has higher expression levels of mir-137, the amount of lsd1 was much lower. 20682795_3 to determine if the 3'-utr region of lsd1 was indeed a functional targetsite of mir-137, a luciferase reporter plasmid harboring either wild-type or mutated predicted region of interaction at the lsd1 3'-utr region was constructed. 23440261_1 the dual luciferase activity assay revealed that mirna-181b downregulated bcl-2 expression. 23440261_2 the results from western blot analysis showed a reduced bcl-2 expression following mir-181b transfection but an enhanced caspase-3 activity in mirna-181b mimic-transfected pdac cells. 23440261_3 we also performed elisa to detect caspase-3 activity and found that caspase-3 activity increased with mirna-181b overexpression, but was reduced following treatment with a mirna-181b inhibitor. 23440261_4 we also performed bioinformatics analyses and found there are 2 potential mir-181b target sites in the bcl-2 3'utr. 26038570_1 h19 interacts with mir-103/107 and regulates mir-103/107 expression 26622795_1 these results confirmed that mir-32 regulated dab2ip by targeting its 3'-utr and suppressing its translation. 26622795_3 in conclusion, the present study demonstrated that mir-32 directly targeted dab2ip in pca, and induced dab2ip-deficient radioresistant human pca cells. 26622795_4 moreover, the findings demonstrated the critical role of mir-32 in inhibiting the mtor-s6k pathway and suppressing autophagy by targeting dab2ip. 18633110_1 mir34a rise is linked to activation of p53 and results in sensitization to apoptosis and impaired nutrient-induced secretion. 18633110_4 treatment with oligonucleotides that block mir34a or mir146 activity partially protects palmitate-treated cells from apoptosis but is insufficient to restore normal secretion. 22375943_2 results showed that mir-22 repressed the luciferase activity through 3'-utr of hdac6 compared with the mir-nc transfection control group. 22375943_3 taken together, these results revealed that mir-22 regulates hdac6 protein expression through its 3'-utr, indicating that hdac6 might be involved in the regulation of adipo/osteogenic differentiation of hadmscs. 22375943_4 transfection of mir-22 mimics into hadmscs resulted in upregulation of hdac6 protein expression without changing the mrna expression of hdac6, confirming that mir-22 suppressed hdac6 expression at a post-transcription level. 25925090_1 negative association was defined between the expression of mir-1294 and the c-myc expression in escc patients . 25925090_2 additionally, it was found that mir-1294 suppress esophageal cancer cells proliferation, migration and invasion capacity through targeting c-myc in vitro. 25925090_4 these results indicate that mir-1294 may suppress c-myc expression through binding to seed sequence at the 3'-utr of c-myc, and c-myc may be a direct target gene of mir-1294. 25925090_5 these results indicated that mir-1294 repressed endogenous c-myc expression in esophageal cancer cells by directly cutting c-myc mrna. 25275594_1 microrna-207 enhances radiation-induced apoptosis by directly targeting akt3 in cochlea hair cells.microrna-207 25275594_3 furthermore, akt3 was confirmed to be a direct target of mir-207. 25275594_4 downregulation of akt3 mimics the effects of mir-207. 25275594_5 mir-207 enhances ir-induced apoptosis by directly targeting akt3 and anti-mir-207 may have a potential role in protecting cochlea hair cells from ir. 26482610_1 thus, these data suggest that meg3 may regulate skp2 at post-transcriptional level to alter p27-mediated cell growth arrest. 21613227_1 in renal mesangial cells, high glucose increased the expression of mir-21, which targeted the 3'-utr of pten mrna to inhibit pten protein expression. in support of the notion that the 3'-utr of pten mrna is a direct targetfor mir-21, we found increased expression of pre-mir-21 and mature mir-21 in the kidney cortex of diabetic mice compared with control mice . 21613227_2 these results indicate that mir-21 may contribute to the reduction in pten that may regulate the pathologic features of diabetic nephropathy. 21613227_3 figure 2.high glucose increases mir-21 to target 3'-utr of pten mrna in mesangial cells. 21613227_4 these results suggest that mir-21 regulates the expression of pten in response to high glucose in mesangial cells. 26692956_3 socs6 is a target of mir-155 in breast cancer cells. 22449976_1 gpc3 as a direct downstream target of mir-219-5p. 22449976_3 these findings indicate that mir-219-5p exerts tumor-suppressive effects in hepatic carcinogenesis through negative regulation of gpc3 expression. 22449976_5 bioinformatics analysis has indicated that gpc3 is a putative target of mir-219-5p. 22449976_6 dual-luciferase assay, qrt-pcr and western blot analysis identified gpc3 as one of the genes directly targeted by mir-219-5p. 22449976_7 a decrease in mir-219-5p expression was shown to be inversely correlated with gpc3 protein expression levels in 45 pairs of hcc tissue samples. 22449976_8 these results suggest that mir-219-5p interacts with gpc3 and negatively regulates its expression. 23252729_1 cse1l is the targetgene of mir-137. 23252729_2 these results suggested a direct interaction between mir-137 and putative binding site on cse1l. 23252729_3 sequence analysis indicated that mir-137 formed complementary base pairing at nucleotides 482- 488 of cse1l 3'-utr, and mir-137 binding site on 3'-utr of cse1l was conserved across eight species . 23252729_4 the results suggested that mir-137 targeted cse1l and regulated its expression at translation level. 23252729_5 these results were similar to that of overexpression of mir-137, suggesting that mir-137 inhibits growth of glioma cells by negatively regulating cse1l expression. 22431721_1 acvr2b is a direct target of mir-192, mir-215, mir-194, mir-141 and mir-200c. 22431721_2 the 2582-c2610 and 9188-c9216 targetregions of mir-215 showed a significant downregulation of the luciferase activity following the transfection of the mir-215 precursor. 22431721_3 mir-192, mir-194, mir-215, mir-200c and mir-141 are downregulated and their common targetacvr2b is strongly expressed in renal childhood neoplasms. 22431721_4 luciferase reporter assays were performed to determine whether the 3'-utr regions of acvr2b were indeed functional targetregions of mir-192, mir-215, mir-194, mir-141 and mir-200c. 26895946_1 these results validate the in silico prediction of cox2 as a target of mir-101b and suggest that cox2 expression could be modulated through wnt-5a signaling via mir-101b. 24898358_1 luciferase reporter assay showed that let-7a directly targets the 3'-utrs of hmga2 in aa-sp+ cells. 24898358_3 these data demonstrated that let-7a directly targets hmga2 through their 3'-utr regions. 24898358_4 these data demonstrated that let-7a directly targets hmga2 through their 3'-utr regions. in the present study, luciferase reporter assay showed that let-7a directly targets the 3'-utrs of hmga2 in aa-sp+. 23226419_2 we propose that cocaine would downregulate zfmor, zfdor1 and zfdor2 via dre-let-7d, since overexpression and knockdowns of opioid receptors altered the expression of dre-let-7d and its precursors at 48 hpf of zebrafish development. 25322725_1 finally, we showed that mir-34a's underlying mechanism during cardiac fibrosis occurs through the targeting of smad4 expression. 25322725_2 our findings provide evidence that mir-34a plays a critical role in the progression of cardiac tissue fibrosis by directly targeting smad4, which suggests that mir-34a may be new marker for cardiac fibrosis progression and that inhibition of mir-34a may be a promising strategy in the treatment of cardiac fibrosis. 25322725_3 as shown in figure 5b and c , transfection of mir-34a precursors clearly reduced luciferase activity for the wild-type reporter but did not for the mutant type smad4 3垄utr, which confirmed that smad4 is directly modulated by mir-34a. 20833636_1 cdk6 had already been implicated as a mirna-107 target . 20833636_2 expression of the kinase was assessed only after overexpressing mirna-107, and it was left open whether cdk6 is regulated solely at the protein level or if cdk6 mrna degradation is induced by mirna-107. 20833636_3 overexpression of mirna-107 led to a decrease of cdk6 reporter activity . 20833636_4 this supports the notion that cdk6 is directly controlled by mirna-107. 20833636_5 in summary, the results indicate that cdk6 and p130 protein levels are under control of mirna-107 but p130 may not be a direct target of this mirna. 20086245_1 furthermore, we demonstrate mir-29 inhibition of cdk6 protein and mrna levels by direct binding to 3'-untranslated region. 20086245_3 ectopic expression of mir-29a, mir-29b, or mir-29c significantly reduced cdk6 expression in mino and hek293t cells. 20086245_4 taken collectively, these data indicate that cdk6 is a direct target of mir-29 family. 20086245_5 these findings demonstrate mir-29 regulation of cdk6 in vivo and frequent overexpression of cdk6 in mcl. 25876995_1 additionally, we showed mir-214 post-transcriptionally regulated the expression of plgf as demonstrated by luciferase reporter assays using wild-type and mutant plgf-3'-utr constructs. 25876995_2 we conclude from these results that plgf has functional mir-214-binding sites in its mrna 3'-utr. 18174313_1 thus, in the presence of high ha density, mir-146a-mediated rock1 silencing may play an important role in suppressing hrpc-associated tumorigenecity, such as cancer cell proliferation. 18174313_2 mature mir-146a could bind to two highly complementary target sequences located in nucleotides 678- 699 and 1504- 1525 of the rock1 gene transcript, indicating that rock1 mrna was a strong target for mir-146a. 18174313_3 our results validated that mir-146a triggered a strong and specific silencing effect on the targeted rock1 gene as predicted. 23176581_1 c-myc as a direct mir-135a targetin rcc cell lines. 23176581_2 to determine whether the 3'-utr of c-myc contained an actual targetsite for mir-135a, we carried out a luciferase reporter assay using a vector encoding the full-length 3'-utr of the c-myc gene. 23176581_3 our data showed that luminescence intensity was significantly reduced in mir-135a transfectants compared to mir-control transfectants . in conclusion, mir-135a was significantly downregulated in rcc clinical specimens and appeared to function as a tumor suppressor in rcc through regulation of c-myc expression and cell cycle progression. 23176581_4 figure 3.direct regulation of myc by mir-135a in the rcc cell lines. 21631941_1 we found that ir induced cardiomyocytes autophagy, together with down-regulation of mir-204 and up-regulation of lc3-ii protein. 21631941_2 and, we have found that lc3-ii protein was regulated by mir-204, using the method of transferring mir-204 mimic or amo-204 into the cardiomyocytes, before. 17621267_2 the relative expression of map3k8 mrna was unchanged by either 5-aza-cdr or by overexpression on il-6. to experimentally verify that map3k8 is a bona fide target of translational regulation by mir-370, several studies were performed. 17621267_3 first, we verified that map3k8 is a targetfor mir-370 using luciferase reporter constructs containing the mir-370 recognition sequence from the 3'-utr of map3k8 inserted downstream of the luciferase gene. 17621267_5 taken together, these data indicate that map3k8 is a biologically relevant target of mir-370 and that upregulation of map3k8 is not a general result of promotion of cell proliferation. 25961369_1 a target prediction program, targetscan,showed that mucin 1 may be a potential target of mir-145. 25961369_2 the 3'-utr of the mucin 1 mrna contains a conserved binding site for the seed region of mir-145. 25961369_3 conversely, in luciferase assays using a plasmid harboring a mutant version of the mucin 1 mrna 3 '-utr ,the luciferase activity of the mutant reporter was unaffected by transfection of mir-145 into a549 and nci-h520 cells . 25961369_4 these data suggest that mir-145 may suppress mucin1 gene expression through the mir-145 binding sequence in its 3 '-utr. 25867061_1 fbxo11 was indicated to be a potential target gene of mir-621, which was also found as a downregulated deg in pcr patients in the training set . 25867061_2 accordingly, fbxo11 was also identified as a mir-621-associated deg by corna analysis. 25867061_3 we found that overexpression of mir-621 could significantly decrease the expression of fbxo11 in hct116 wt cells, but not in hct116 dicer-/- cells , suggesting that the repression of fbxo11 by mir-621 is dicer-dependent. 25867061_4 in accordance, mir-621 overexpression significantly repressed the activity of a luciferase reporter fused to fbxo11 3'-utr, but not the one fused to fbxo11 3'-utr mutant in which mir-621-recognition site was deleted . 25867061_5 all these data strongly support that mir-621 may repress fbxo11 expression through recognition of its binding site within fbxo11 3'-utr in human cancer cells. 26437365_1 from this screen we identified and characterized mir-148a as a negative regulator of ldlr expression and activity and defined a sterol regulatory element-binding protein 1 -mediated pathway through which mir-148a regulates ldl-c uptake. 26437365_2 here we show that mir-148a directly controls ldlr activity and is transcriptionally activated by srebp1c in vitro and in vivo. 26206083_1 using computational prediction, we found that the 3'utr of carma1 mrna contains one mir-539 binding site. 26206083_2 the luciferase activity assays indicated that mir-539 mimics significantly inhibited and anti-mir-539 significantly increased the reporter activity of the wild-type but not that of the mutant carma1 3'-utr, suggesting that mir-539 directly binds to this site . 26206083_3 overexpression of mir-539 dramatically decreased carma1 at the mrna and protein level, whereas anti-mir-539 increased carma1 levels in k1 cells. 22010139_1 mmp-2 and mmp-9 were identified as potential target for mir-29a and mir-133a, respectively, and mmp-2 was subsequently verified as a mir-29a targetin vitro. 22010139_2 lastly, to examine the relationship between total mmp-2 protein abundance and mir-29a expression in the aortic specimens, linear least-squares regression modeling was again performed, and a significant inverse relationship between mir-29a expression and total mmp-2 abundance was identified ; indicating that as mir-29a decreased, the relative abundance of mmp-2 increased . 22010139_3 the results demonstrated that overexpression of mir-29a attenuated total mmp-2 protein abundance, while overexpression of anti-mir-29a enhanced total mmp-2 protein abundance. 26166761_1 mir-27a*, mir-378, and mir-30e directly target perforin and/or grzb, which are significantly down-regulated in denv patients. 21048943_1 dkk-1 and dact3 are direct targetcandidates of mir-31. 21048943_2 collectively, these experiments strongly suggested that mir-31 modulates dkk-1 and dact3 via post-transcriptional and translational-inhibitory mechanisms in cultured normal respiratory epithelia and lung cancer cells. 21048943_3 collectively, these experiments strongly suggest that mir-31 directly interacts with 3'-utrs of dkk-1 and dact3. 24884974_3 among these p53/mir-34 associated processes, apoptosis and cell cycle arrest are known as essential for p53/mir-34-mediated tumor suppression. 26662313_1 a negative correlation between mir-27a and bak was also observed in normal breast epithelial cell line mcf-10a and bc cell lines, suggesting that the bak is the potential target of mir-27a. 26662313_2 these results suggest that the gene of bak is a functional target of mir-27a, which may play an essential role for the sensitivity of tumor cells to chemotherapeutic agents. 17150553_1 in this study, we show that microrna-196 inhibits hoxb8 expression in myeloid differentiation of hl 60 cells. 17150553_2 mir-196 has perfect complementarity with targetsequence of 3'-utr in hoxb8 mrna. 17150553_3 exogenous expressed mir-196 repressed expression of hoxb8 via cleaving mrnas. 17150553_5 these results suggest that mir-196 participates in myeloid differentiation of hl60 cells via regulation of hoxb8 expression. 19079265_1 mir-29 mirnas targetp85alpha and cdc42. 19079265_2 another potential target of mir-29 mirnas was the cdc42 mrna, which contains two targetsites for mir-29 . 19079265_3 the cdc42 protein level fell in hela cells that were transfected with mir-29 mirnas, as determined by western blotting . 26462877_1 these results indicate that mir-150 preferentially targets c-myb translation. 21901135_1 interestingly, erk5 is the most widely reported direct target of mir-143, which is downregulated by mir-143 overexpression , . 21901135_2 importantly, transient overexpression of mir-143 mimetics in hct116 , sw480 and dld-1 colon cancer cell lines has been shown to down-regulate erk5 steady-state levels. 24574214_1 overexpression of mir-451 down-regulated lu-ciferase activity with the target sequences of cpne3 and rab5a downstream of the firefly luciferase gene, whilesuppression of mir-451 up-regulated luciferase activity . 24574214_2 the expression of rab5a was negatively correlated with the expression of mir-451 inra patients ,indicating that rab5a is regulated by mir-451 in raneutrophils. 26840018_1 further, oncogene ccnd1 was revealed to be a putative target of mir-326, which was inversely correlated with mir-326 expression in nsclc. 26840018_2 here, we reported that mir-326 is indeed suppressed in primary lung cancers compared with the matching adjacent normal tissues, and found 3'-utr of the human ccnd1 mrna is really a target of mir-326. 26840018_3 these results suggest that mir-326 binds directly to the predicted binding site in the ccnd1 3使-utr. 26840018_4 mir-326 targets ccnd1 in lung cancer cells and negatively expressed with ccnd1. 24098322_1 here, we validated tnf-alpha as the target of mir-181a by a dual luciferase assay. 24098322_2 our study provides the first evidence of the role of mir-181a in adipocyte differentiation by regulation of tnf-alpha, which may became a new therapeutic target for anti-obesity drugs. in this study, we demonstrated the ability mir-181a to inhibit tnf-alpha expression by targeting the 3'-utr of its mrna, thus affecting adipogenesis. 24098322_3 thus, tnf-alpha was initially confirmed as the target of mir-181a. 24098322_4 this study demonstrates that mir-181a is a novel regulator of tnf-alpha in porcine adipocytes. 19780876_3 nevertheless, the ppar-alpha protein level decreased and increased significantly after the overexpression and knockdown of mirna-10b, respectively . 19780876_4 thus, these results demonstrated that mirna-10b directly recognized the 3'-utr of the ppar-alpha transcript and mediated its expression post-transcriptionally. 22245693_1 hmga1 can be regulated negatively by mir-26a at both transcriptional level and protein level in sw1990 and panc-1 cells. 22245693_3 to validate whether hmga1 is a direct target of mir-26a, we mutated the mir-26a binding site in the 3'utr of hmga1 and observed loss of repression. 23546867_1 together, these results support the hypothesis that mcl-1 is a direct target of mir-193a-3p. 23546867_2 these results together confirm that mcl-1 is a direct target of mir-193a-3p and that the region between 1,585 and 1,591 bp downstream of the stop codon is a targetsequence to which mir-193a-3p bind. in short, the overlap in phenotypes caused by either mcl-1 downregulation or expression of mir-193a-3p, strongly suggest that mcl-1 downregulation is a critical point in mir-193a-3p-induced apoptosis. 23546867_3 together, these observations strongly suggest that mcl-1 downregulation is a critical step during apoptosis triggered by mir-193a-3p. 26287602_1 figue 6: chd5 was a direct target of mir-454. 26287602_2 ectopic expression of mir-454 inhibited the chd5 mrna and protein expression . 26239616_3 the expression of mir-132 was negatively correlated with the protein expression levels of mecp2 and bdnf, whereas mecp2 expression was positively correlated with bdnf expression in the peripheral blood of patients with mdd. 26239616_4 overexpression of mir-132 significantly reduced the expression levels of mecp2, at both the mrna and protein level, whereas downregulation of mir-132 increased the mrna and protein expression levels of mecp2. 26239616_5 these results indicate that mecp2 and mir-132 may regulate hippocampal bdnf expression in an opposite manner, suggesting that homeostatic interactions between these factors control hippocampal bdnf expression. 26572867_1 here we show post-transcriptional regulation of shank3 expression by three micrornas , mir-7, mir-34a, and mir-504. 26572867_3 together, these results suggest that mir-7, mir-34a, and mir-504 directly bind to the shank3 3'utr and downregulate its expression. 26572867_4 we found that mir-7, mir-34a, and mir-504, three mirnas with altered expression profiles in multiple neuropsychiatric disorders, directly regulate shank3 expression. 26647829_1 a luciferase reporter assay demonstrated that mir-145 was able to bind to the 3'-untranslated region of fscn1 mrna. 26647829_2 luciferase activity levels were significantly reduced in ags cells with the wild type 3'-utr of fscn1 mrna co-transfected with mir-145 mimics; however, luciferase activity levels did not change in ags cells with mutant type 3'-utr of fscn1 mrna co-transfected with mir-145 mimics, compared with the control group , indicating that fscn1 is a direct target gene of mir-145. 26647829_3 therefore, the results suggest that mir-145 negatively regulates the protein expression of fscn1 in ags gastric carcinoma cells, perhaps by directly binding to the 3'-utr of fscn1 mrna. 26647829_4 the present study identified fscn1 as a target of mir-145 in gastric carcinoma cells, and demonstrated that mir-145 was downregulated, whereas fscn1 was upregulated in gastric carcinoma cell lines, as compared with normal gastric mucosal epithelial cells. 20826792_1 we presentcompelling evidence that tiam1, a guanidine exchange factor of the rac gtpase, is a direct target of both mir-21 and mir-31. 20826792_2 thus mir-21 and mir-31 appear to control tiam1 expression mainly through repression of the protein translation, not degradation of the mrna. 20826792_4 5, mir-21 and mir-31 also down-regulated tiam1 in dld1 and sw480 cells . 20826792_5 importantly, we found that transfection of mir-21 did not cause a significant change in mature mir-31 level, and vice versa . 20826792_6 therefore, mir-21 and mir-31 do not influence the expression levels of each other and likely impact the expression of tiam1 independently. 20826792_7 this strongly suggests that mir-31 also directly represses tiam1 translation. 20826792_8 these data further substantiate our model that repression of tiam1 is a critical component in mir-21/mir-31 regulation of migratory and invasive properties of lim 1863 cells. 21947305_1 the basal levels of the anti-apoptotic protein bcl-w were high in bel-7402/5-fu cells and mir-195 overexpression repressed bcl-w protein level and inhibited the luciferase activity of a bcl-w 3'untranslated region-based reporter construct in both bel-7402/5-fu and bel-7402 cells. 26512958_1 taken together, these data demonstrate that mir-371a-5p enhance bag3 protein expression, and that the interaction of mir-371a-5p with human bag3 3'-utr critically depends on the presence of the g2252 variant. 26512958_2 intriguingly, this posttranscriptional pathway regulating bag3 protein expression is altered by the presence of the g2252c variant in the 3'-utr of human bag3, which is frequently present in a cohort of ttc patients, suggesting that epi-induced mir-371-5p and bag3 may potentially represent new molecular components in the disease pathogenesis of ttc. 24789910_3 skeletal muscle-specific mir-486 overexpression in dmdmdx-5cv animals decreased levels of dock3, reduced pten expression, and subsequently increased levels of phosphorylated akt, which resulted in an overall beneficial effect. 22540680_6 thes data suggest that mir-214 inhibits the emt by directly targeting the twist gene. 26229485_1 furthermore, sox9 was confirmed as a direct target of mir-32, using a luciferase reporter assay. 26229485_2 finally, sox9 was identified as a direct target of mir-32, using a luciferase reporter assay. 26229485_3 these data indicated that sox9 was a direct target of mir-32 in nsclc. 26582573_1 according to the data of mirtarbase, cdkn1a might be a candidate target gene of mir-96. in addition, luciferase reporter and western blot assays respectively demonstrated that mir-96 could bind to the putative seed region in cdkn1a mrna 3'utr, and significantly reduce the expression level of cdkn1a protein. 26582573_2 taken together, these data demonstrated that mir-96 could negatively regulate the expression of cdkn1a in both bc cells and tissues. 25531114_1 overexpression of mir-338-3p inhibited hif-1alpha 3'-utr luciferase activity and hif-1alpha protein levels in hepg2, smmc-7721, and huh7 cells. 26617940_1 we subsequently identified that akt1 was a target gene of mir-185. 26617940_2 re-expression of akt1 could partially rescue the inhibitory effects of mir-185 on the capacity of nsclc cell proliferation and motility. 26617940_3 these data suggest that mir-185 negatively regulates akt1 expression in nsclc cells. 26617940_4 taken together, the cancer suppressor role of mir-185 in nsclc is at least partially by inhibiting its target gene akt1. 26648452_1 these data reveal that fgf-21 could be negatively regulated by mir-212 and/or under conditions of lipogenesis. 26648452_2 these data clearly indicate that fgf-21 is a target gene of mir-212 involved in lipogenesis. 24356489_1 forced over-expression of mir-23a/b decreased the level of fas protein. 24356489_2 moreover, over-expression of fas rescued the pro-proliferation effect of mir-23, indicating fas is a direct mediator of mir-23 functions. 24356489_3 furthermore, contrast to mir-23a/b which was up regulated, the fas expression level was down-regulated and inversely correlated with mir-23 in split radiation induced lymphoma tissue samples. 24356489_4 finally, our data also indicates that mir-23a could repress fas much more potent than mir-23b and the additional region besides conserved seed pairing enables mir-23a's higher regulation.fig. 24356489_5 3 the predicted mir-23a/b binding site on murine fas mrna 3'utr and the mutation strategy is shown. 24356489_6 a dual luciferase assay of nih3t3 cells co-transfected with the firefly luciferase constructs containing the wild type or 258-264 mutated fas 3'-utr and mir-23a/b mimics or scrambled negative control . 24356489_7 mir-23a/b mimics inhibit endogenous fas expression in el4 cells as detected by facs assay. 24356489_10 mir-23a/b mimics inhibit endogenous fas expression in el4 cells as detected by qrt-pcr. 11919683_1 we found that the mouseklhl1as rna is not spliced and terminates in a polyadenylation site in the klhl1 promoter region, whereas both the present and previous work show that human klhl1as is highly variably spliced into processed transcripts that contain up to six exons. 11919683_4 the evolutionary conservation of this antisense/sense transcriptional organization strongly indicates that klhl1as transcripts play a significant biological role in both human and mouse presumably as a regulator of klhl1 expression. 26617733_1 as a result, foxm1 was a binding target of mir-370,overexpression of mir-370 in mg63 and u2os cells remarkably decreased the protein level of foxm1. 26617733_2 next, we further demonstrated whether foxm1 was a direct target of mir-370 by using luciferase reporter assay. 26617733_3 the results showed that overexpression of mir-370 significantly decreased the luciferase activity of pmir-foxm1 3'-utr wt, where as mutation of the mir-370-binding site in the foxm1 3'-utr abolished the effect of mir-370 . 26617733_4 these results suggested that foxm1 was directly and negatively regulated by mir-370. 25379703_1 cdc42, a mediator of the pi3k pathway, was identified as a novel mir-18a target. 25379703_2 overexpression of mir-18a reduced cdc42 expression, and a luciferase assay confirmed that mir-18a directly targets the 3'utr of cdc42. 25379703_3 mir-18a mimics had a similar effect on proliferation as a small molecule inhibitor of cdc42. 25379703_4 inhibition of cdc42 expression is likely to be a key mechanism by which mir-18a impairs cancer cell growth, with a target protector experiment revealing mir-18a influences proliferation via direct inhibition of cdc42. 25379703_5 inhibition of ccnd1 by mir-18a may also assist in this growth-suppression effect. 26505789_1 these results indicated that mir-351 reduced endothelial cell survival and suppressed angiogenesis through targeting stat3 in vitro. 26497367_1 we hypothesized that mir-124 and mir-506 may directly target dnmt3b and may indirectly target dnmt1. 26497367_2 the above results may preliminarily indicate that dnmt3b is a direct target and that dnmt1 is an indirect target of mir-124 and mir-506. 25362258_1 e2f2 was identified as a direct target of mir-31. in our study, we have verified that e2f2 is a direct target of mir-31 using western blotting and luciferase reporter assay. 25362258_2 these results demonstrates that e2f2 expression is negatively regulated by mir-31. 25362258_3 data of luciferase reporter assay and western blot demonstrates that e2f2 is a direct target of mir-31. 25362258_4 these results demonstrates that mir-31 regulates the proliferation of colon cancer by targeting e2f2. 25698447_2 indeed, antagonizing mir-3189-3p in the context of dna damage derepressed cdk2 and ccna2, and to a lesser extent cdc25a . 26617783_1 moreover, mir-323 could directly bind to bri3 3'-utr. 26617783_2 this study indicated that mir-323 might regulate ischemia/reperfusion-induced rat neuronal cell death via targeting bri3. 26617783_3 these results showed that mir-323 bound directly to a specific site in the 3'-utr of bri3 mrna . 26617783_4 these data suggest that mir-323 suppressed the expression of bri3 in a post-transcriptional manner. 25115396_1 golm1 was directly regulated by mir-27b in pca cells. 25115396_2 golm1 was a direct target of mir-27b in pca cells. 25115396_3 our present data clearly showed that golm1 was directly regulated by tumor-suppressive mir-27b in pca cells. 25118289_2 a combination of bioinformatics, pcr array, dual-luciferase reporter assay, and western blot analysis revealed that fas ligand and death receptor 5 are the direct targets of mir-21. 23355420_1 in the present study, we constructed a luciferase reporter system and identified hef1 as a direct target of mir-145. 23355420_2 taken together, these findings indicate that hef1 promotes emt and bone invasion in prostate cancer by directly targeted by mir-145, and mir-145 suppresses emt and invasion, at least in part, through repressing hef1. 23355420_3 thus, these observations indicated that mir-145 directly targeted hef1 through interacting with the 3'-utr. 26221232_1 p53 was a direct target of mir-300 in breast cancer cells. 22564414_1 genetic evidence obtained in the mouse confirmed the importance of satb2 regulation by mir-34b/c. 22564414_2 several lines of evidence verified that satb2 is a bona fide target of mir-34s. 22564414_3 these data provide an in vivo verification of the importance of satb2 regulation by mir-34b and -c in osteoblasts in vivo. 22564414_4 the direct regulation of satb2 by mir-34s explains why these mirnas regulate osteocalcin, bsp, and possibly other genes whose expression is controlled by runx2 and satb2 or atf4 and satb2. 20582318_1 although target mrnas frequently have multiple copies of mirna target sites in their 3'-utr , examination of the nocturnin mrna sequence revealed a single potential target sequence for mir-122 in its 3'-utr . 20582318_2 these results indicated that nocturnin is a potential direct target of mir-122, and mir-122 recognizes the putative recognition site present in the nocturnin 3'-utr. 20582318_3 these data were consistent with previous reports that listed nocturnin mrna as one of a set of mrnas that were up-regulated by knocking down mir-122 in vivo , . 20582318_4 although overexpression of mir-122 did not affect the rna level of the nocturnin reporter gene , the knock down of mir-122 was able to significantly increase nocturnin mrna levels in mouse liver. 20582318_5 our data thus demonstrate that this robustly rhythmic expression of nocturnin in liver is shaped, at least in part, by mir-122. 18829576_3 these phenotypes are dependent on two of the mir-21 targets validated in this study, hnrpk and tap63. 22885155_1 phosphatase and tensin homolog was a direct target of mir-26a. 22885155_2 mir-26a enhances metastasis potential of lung cancer cells via akt pathway by targeting pten. 22885155_4 taken together, all these results strongly indicated that pten was a direct target of mir-26a. 25633921_1 mir-21 and spry2 were expressed in the mm cell lines. 25633921_2 in the rpmi 8226 and km3 cell lines, mir-21 was highly expressed and spry2 was expressed at a low level. 25633921_3 however, in the u-266 cell line, in which a low level of mir-21 was detected, spry2 was expressed at a high level. 25633921_5 western blot analysis revealed that in the mm cell lines with a high level of endogenous mir-21 expression, spry2 was expressed at a significantly lower level. 25633921_6 by contrast, in the u-266 cell line with low endogenous mir-21 expression, spry2 was expressed at a significantly higher level . 26646586_1 we investigated whether overexpression of mir-125a or mir-125b was sufficient to reduce eif4ebp1 levels in skov3 and ovcar-429 ovarian cancer cells. 26646586_2 treatment with an inhibitor of mir-125a or mir-125b enhanced eif4ebp1 mrna and protein levels. 26646586_3 taken together, these results show that both mi mir-125a and mir-125b can directly influence eif4ebp1 through specific binding to its 3'-utr. 25138213_1 hdac3 showed a positive feedback loop with mirnas such as mir-200b, mir-217, and mir-335. 25138213_2 mir-200b, mir-217, and mir-335 negatively regulated the expression of mir-326 and the invasion and migration potential of cancer cells while enhancing the apoptotic effect of anti-cancer drugs. 25138213_3 targetscan analysis predicted mir-200b and mir-217 as negative regulators of cancer-associated gene, a cancer/testis antigen, which is known to regulate the response to anti-cancer drugs. 25138213_4 hdac3 and mir-326 acted upstream of the cancer-associated gene. 22457808_1 figure 6 identification of mir-143 and mir-145 target. 22457808_3 3'utr luciferase reporter assay indicated that fascin homolog 1 could be co-regulated by mir-143 and mir-145. 22457808_4 luciferase reporter assay for 3'-utr of fscn1 regulated by mir-143 and mir-145. 22457808_5 co-transfection of mir-143 and mir-145 showed a synergistic effect on suppressing the expression of fscn1. 22457808_6 and our result also indicated that 3'-utr of fscn1 could be co-regulated by mir-143 and mir-145. 22457808_7 with these researches, we suggested that mir-143 and mir-145 could control oncogenic fscn1 and take part in the modulation of metastases. 26794609_1 col1a2 and vegf-a contained a conserved binding site of mir-29a in different species, suggesting that col1a2 and vegf-a were putative target genes. 26794609_2 on performing a luciferase reporter assay, we showed that luciferase activity was significantly reduced in cells co-transfected with the wild-type col1a2 or vegf-a 3'-utr and increasing concentrations of mir-29a mimics. 26794609_3 conversely, we found that mir-29a inhibitor significantly induced luciferase activity in cells transfected with wild-type col1a2 or vegf-a 3'-utr; after upregulation of mir-29a, the protein levels of col1a2 and vegf-a were notably reduced, while mir-29a knockdown led to significant upregulation of col1a2 and vegf-a protein levels . 26794609_4 these findings indicate that col1a2 and vegf-a are two direct targets of mir-29a, and the protein expression of col1a2 and vegf-a was negatively mediated by mir-29a in bj cells. 18568019_1 rescue experiments indicated that the effects of plzf and mir-146a are mediated by mir-146a and cxcr4, respectively. 18568019_2 our data indicate that megakaryopoiesis is controlled by a cascade pathway, in which plzf suppresses mir-146a transcription and thereby activates cxcr4 translation. 18568019_4 plzf is a transcriptional repressor of mir-146a expression. 18568019_5 mir-146a downregulates cxcr4 and impairs cell proliferation and differentiation/maturation. 18568019_6 luciferase-based promoter assays and plzf silencing studies indicate that the progressive increase in plzf expression during megakaryopoiesis represses mir-146a transcription. 18568019_7 to demonstrate a direct interaction between mir-146a and cxcr4 mrna, we inserted the following constructs downstream of a renilla luciferase reporter cdna: 1 the full-length 3'-utr of cxcr4 mrna . 18568019_8 muts2 or muts3 reporter vector was not affected, , indicating that mir-146a interferes with cxcr4 mrna translation through a direct interaction with s2 and s3 sites in the 3'-utr-fl. 23583431_1 we identified manganese superoxide dismutase messenger rna as a direct target of mir-212, and observed an inverse correlation between the level of mir-212 and mnsod protein in colorectal tumor samples. 23583431_2 mnsod was identified as a novel major target of mir-212, which appears to play an important role in regulating emt via mnsod. 23583431_3 taken together, these results suggest that mnsod is a direct target of mir-212 and the 3' utr of mnsod is the functional target site for mir-212. in this study, we determined that mir-212 regulates the metastasis and emt of crc by targeting mnsod. 17911264_1 tumor protein 53-induced nuclear protein 1 is a proapoptotic stress-induced p53 target gene. 17911264_2 tp53inp1 expression is repressed by the oncogenic micro rna mir-155, which is overexpressed in pdac cells. 23376592_1 the expression of the previously reported putative gene targets of mmu-mir-466h-5p, smo, stat5a, dad1, birc6, and bcl2l2 in anti-mir-466h and negative control cho cells is shown in figure 5. the mrna levels of smo, stat5a, dad1, birc6, and bcl2l2 genes were not significantly changed at 192 hours in the negative control cho cells compared to anti-mir-466h cho cells , but were significantly reduced at 216, 226, and 236 hours of cell culture. 23376592_2 it is, therefore, likely that the inhibition of the activated mmu-mir-466h-5p in anti-mir-466h cho cells shown in figure 4 leads to increased levels of the anti-apoptotic genes: smo, stat5a, dad1, birc6, and bcl2l2 as seen in figure 5 which delays the activation of caspase-3/7 and onset of apoptotic cascade shown in figure 3. 20118412_2 these results confirm that smad4 gene is a mir-224 target mir-224 regulates smad4 gene expression at the posttranscriptional level . 20118412_3 these results further suggest that smad4 is a target of mir-224 and mediates the roles of mir-224 to influence gc proliferation and function. 19739117_6 microrna-100 was predicted to target plk1 mrna, which was indeed under-expressed in c666-1 cells; inversely correlating with plk1 expression. 19739117_7 using luciferase constructs containing the 3'-utr of plk1 sequence, we document that mir-100 can directly target plk1. 19739117_8 hence, our data demonstrate for the first time, that under-expressed mir-100 leads to plk1 over-expression, which in turn, contributes to npc progression. 26893485_1 to associate the mir-223 up-regulation with the down-regulated igf-1r, and to confirm the targeted inhibition of igf-1r by mir-223 in mc3t3-e1 cells, we then investigated the regulation by mir-223 up-regulation on the igf-1r expression in mc3t3-e1 cells. 26893485_2 we confirmed the targeting inhibition of igf-1r expression by mir-223 in mc3t3-e1 cells. 22022489_1 pathways involving metabolic processes, terpenoid and sterol metabolism were selectively affected by concomitant regulation by mirnas and mrnas, and srebf1 was validated as a target of mir-21. 22022489_2 messengerrna levels of srebf1 increased by about 30% after mir-21 knock-down . 22022489_3 also srebp1 protein levels increased approximately 50% after mir-21 knock-down compared with a lna-scr . 22022489_4 these data were consistent with srebf1 being a targetgene of mir-21. in summary, out of the three tested target, srebf1 was conclusively found to be a functional target of mir-21. 26559153_1 the cyclin-dependent kinase 4 was verified as a mir-539 target gene using dual-luciferase reporter assays, quantitative rt-pcr and western blotting and was involved in mir-539-regulated npc cell growth. 26559153_2 in hek293 cells cotransfected with the reporter plasmids and mir-539 mimic or nc duplex, the luciferase activity of the reporter that contained wild-type 3'-utr was significantly suppressed by mir-539 mimic, but the luciferase activity of mutant reporter was unaffected , indicating that mir-539 may suppress gene expression through mir-539 binding sequence at the 3'-utr of cdk4. 26559153_3 together, the results show that mir-539 could regulate the expression of endogenous human cdk4 by directly targeting the 3'-utr of cdk4 mrna, and human cdk4 is a new target of mir-539. 26338965_1 this effect is mediated trough mir-146b-5p, which inhibits il-6 expression through a specific sequence at the il-6 3'-utr. 26338965_2 these results indicate that mir-146b-5p represses il-6 expression in breast stromal fibroblasts. 26338965_3 this demonstrates that the mir-146b-5p-dependent repression of il-6 is mediated through binding to its seeding sequence in the il-6 3'-utr. 26338965_4 we have recently shown that p16 is a positive regulator of mir-146b-5p , and the present data indicate that this microrna inhibits il-6, whose mrna contains a specific mir-146b-5p binding site in its 3' utr. 21947487_1 ndst1 was a direct targetgene of mir-191. 21947487_2 ndst1 expression level was inversely correlated with mir-191. 21947487_3 these findings suggested that mir-191 could directly bindto the 3'-utr of ndst1, supporting that ndst1 was a direct targetgene of mir-191. 21947487_4 as a result, we found that the endogenous ndst1 also showed opposite trend to the mir-191 level, both on mrna level and protein level . 21947487_5 these data indicated that mir-191 could negatively regulate the endogenous ndst1 expression in mgc803 cells, supporting that ndst1 was a direct target gene of mir-191. 26158762_1 these results indicate that mir-101 functions to directly suppress dusp1 gene expression through the mir-101-binding sequence located at the 3'-utr of the dusp1 mrna. 26573744_1 among several candidate target genes of mir- 340, we chose myo10 as the object of further study. 26573744_2 moreover, the expression of myo10 was significantly increased after blocking mir- 340 expression thus, we confirmed that mir- 340 is expressed at a low level in breast cancer cells and myo10 is a direct target of mir- 340, which negatively regulates its expression. 18308936_1 ectopic expression of let-7g in k-ras -expressing murine lung cancer cells induced both cell cycle arrest and cell death. 18308936_2 in tumor xenografts, the authors observed significant growth reduction of both murine and human non-small cell lung tumors when overexpression of let-7g was induced from lentiviral vectors. in let-7g expressing tumors, reductions in ras family and hmga2 protein levels were detected. 26722309_3 using the dual luciferase reporter assay, a direct target relationship between mir-128 and vegf-c was revealed in both t24 and 5637 cell lines. 24466011_4 further, we found h19 positively correlated with its derivate mir-675 expression and reduction of h19 inhibited mir-675 expression. 24466011_5 bioinformatics and luciferase reporter assays showed that mir-675 modulated cadherin 13 expression by directly targeting the binding site within the 3'-utr. 24466011_6 finally, introduction of mir-675 abrogated h19 knockdown-induced cell invasion inhibition in glioma cells. 24466011_7 to our knowledge, it is first time to demonstrate that h19 regulates glioma development by deriving mir-675 and provide important clues for understanding the key roles of lncrna-mirna functional network in glioma. 24286315_2 the tumor suppressor pten was identified as a mir-221 target; overexpression of pten abrogated the aforementioned mir-221-induced malignant phenotypes of the cells. 25500542_1 we show that mir-206 directly targets the oncogenes kras and annexin a2 , thereby acting as tumor suppressor in pdac cells by blocking cell cycle progression, cell proliferation, migration and invasion. 25500542_2 hence, the above findings confirm that both, kras and anxa2, genes are indeed novel direct targets of mir-206 in pdac cells. 25500542_3 we further demonstrate that mir-206 inhibits the invasive capacity of pdac cells through combinatorial targeting of anxa2 and kras genes. 22174674_1 we found that three kshv mirnas, mir-k12-1, 3 and 4-3p, were responsible for the targeting of casp3.potential 16549775_1 we showed that hoxa1 is a direct target of mir-10a. 16549775_2 to confirm in vivo these findings, we transfected k562 cells with the pre-mir-10a precursor by using nucleoporation and measured hoxa1 mrna expression by rt-pcr and hoxa1 protein levels by western blotting. 16549775_4 a significant reduction at the mrna and protein levels for hoxa1 was found for k562 cells transfected with the mir-10a precursor but not with the negative control . 16549775_5 these data indicate that mir-10a target hoxa1 in vitro and in vivo. 19665999_1 in human cell lines, we found that mir-205 down-regulates the expression of lrp1 by targeting sequences in the 3'utr of lrp1 mrna. 19665999_2 to further investigate whether mir-205 affects u87 and sk-lu-1 cell migration through down-regulation of lrp1, we conducted three-dimensional cell migration assays using matrigel pre-coated transwell chambers. 19665999_3 we found that mir-205 transfection into u87 and sk-lu-1 cells decreases cell migration approximately 25% in both cell types, compared to controls , indicating that mir-205 is a potential suppressor of tumor metastasis in glioblastoma and lung cancer cells. 19665999_4 these results support that lrp1 is specifically regulated by mir-205 . 12095916_1 mestit1 is a paternally expressed non-coding rna that may be involved in the regulation of mest expression during development. 19589872_1 antisense oligonucleotides of has-mir-222 could increase reporter gene expression by targeting the 3' untranslated regions of cdkn1c/p57kip2 mrnas as well as increase cdkn1c/p57kip2 protein levels . in conclusion, our results suggest that a subset of mirnas play a key role in gene reprogramming during escs decidualization and that hsa-mir-222 participates in esc differentiation by regulating escs terminally withdrawing from the cell cycle. 20213048_1 down-regulation of malat1 induced the expression of caspase-3, -8, bax, and suppressed the expression of bcl-2 and bcl-xl in caski cells. 20213048_2 down-regulation of malat1 induced the expression of caspase-3, -8, bax, and suppressed the expression of bcl-2 and bcl-xl. 26215566_2 one potential target of mir-431 was smad4, a protein of interest given that smad4 negatively regulates myogenic differentiation. 26215566_4 this inhibition was specific, as deletion of the mir-431 site on the smad4 3- utr abolished this repression. 26215566_5 these results indicated that mir-431 is unlikely to target smurf1, at least in muscle cells, thus ruling out the possibility that mir-431 regulates smad4 levels indirectly via smurf1-regulated proteolysis. 20829195_2 all the mimics that potently knocked down mcl1 expression, except mir-605 and mir-744*, substantially reduced the luciferase activity. 22270966_2 similar results were found in tumorigenesis assays performed in nude mice. 22270966_6 overexpression of mir-223 in gastric cancer cell lines decreased fbw7 expression at the translational level and decreased fbxw7/hcdc4-driven luciferase-reporter activity. 23226307_1 we reasoned that if the phenotype induced by tbx5 over-expression was due, at least in part, to increased expression of mir-218, the co-injection of mo-218 should rescue the tbx5 gain of function phenotype. 23226307_3 this result strengthened our hypothesis that the effect of tbx5 over-expression on heart development might, at least in part, be be mediated by mir-218. 23226307_4 we found correlated expression of tbx5 and mir-218 during cardiomyocyte differentiation of mouse p19cl6 cells. 26135959_1 subsequently, it was demonstrated that overexpression of mir-7 notably inhibited the protein expression of pax6, while inhibition of mir-7 enhanced the protein expression of pax6 in nsclc a549 cells. 26135959_2 further investigation identified pax6 as a target of mir-7 in a549 nsclc cells. 26135959_3 ina ddition, the overexpression of mir-7 significantly inhibited a549 cell proliferation and invasion, which was reversed by upregulation of pax6. 17468766_2 we identified specific targets of mir-133: rhoa, a gdp-gtp exchange protein regulating cardiac hypertrophy; cdc42, a signal transduction kinase implicated in hypertrophy; and nelf-a/whsc2, a nuclear factor involved in cardiogenesis. 26817584_1 in addition, we found high expression of smad4 in hcc gr cells, which have lower expression of mir-130a-3p , suggesting that smad4 could be a target of mir-130a-3p. 26817584_2 bioinformatics analysis indicated that the smad4 3'-utr harbors potential mir-130a-3p target sites,we found that it has a significant reduction in luciferase activity with wild-type smad4, but not mutant smad4, in hepg2 gr cells transfected with mir-130a-3p mimic . 26817584_3 consistently, mir-130a-3p inhibitors treatment led to increased luciferase activity with wild-type smad4 in hepg2 cells . 26817584_4 taken together, these findings further validate that smad4 is a downstream target of mir-130a-3p. 26552593_1 microglia transfected with mir-367 had dramatically reduced irak4 expression , which suggests that mir-367 inhibits erythrocyte lysate-induced irak4 expression in microglia. 19422085_1 mirs -93 and -106b targeted and inhibited p21, while mir-25 targeted and inhibited bim. 19422085_2 western blotting revealed that p21 protein expression was sharply reduced by mir-93 and mir-106b mimics, and correspondingly, that p21 protein expression was sharply increased by mir-93 and mir-106b inhibitors. 19422085_3 luciferase reporter activity was significantly reduced by mirs -93 and -106b but not by mir-25, suggesting that mirs -93 and -106b binddirectly to the p21 3'utr and inhibit p21 protein expression. 19422085_4 western blotting revealed that the expression of both bim isoforms was reduced by a mir-25 mimic and increased by a mir-25 inhibitor. 19422085_6 qrt-pcrs showed that p21 mrna expression was diminished approximately 30% by the mir-93 mimic and 40% by the mir-106b mimic, vs. 94% by the control p21-sirna. 19422085_7 bim mrna expression did not change following transfection of a mir-25 mimic. 25592039_3 moreover, mir-29b increased irf1 expression, and the inhibition of mir-29b suppressed ifn-纬-induced apoptosis. 26272601_1 based on these results, we hypothesized that bmk1 was a target of mir-429 in glioma. 26272601_2 taken together, these results indicate that mir-429 affects bmk1 expression by directly targeting its 3'-utr. 26272601_3 these results strongly suggest the clinical correlation between mir-429 and bmk1. 26272601_4 taken together, these findings strongly suggest that mir-429 downregulation was due to hypermethylation in the promoter region of the mir-429 gene. 26459798_1 furthermore, pak6 overexpression was regulated by microrna - 328. luciferase reporter assay and western blot analysis indicated that pak6 was directly targeted by mir- 328. 26459798_2 these characteristics indicate that mir-328 directly targets pak6. 26238082_1 tissue specimens and cell lines were explored for mir-219-5p inhibition on colon cancer proliferation, migration, invasion, apoptosis and drug resistance by targeting sall4. in the present study, we investigated the aberrant expression of mir-219-5p and sall4 in colon cancer specimens, and confirmed that sall4 was the direct target of mir-219-5p. 26238082_2 moreover, western blot assay additionally supported the results of dual luciferase assay that upregulation of mir-219-5p inhibited sall4 expression and vice versa , confirming sall4 was a direct target of mir-219-5p. 26238082_3 all the outcomes confirmed that mir-219-5p inhibited colon cancer proliferation and g0/g1 cell cycle arrest by targeting sall4. 25181679_1 the 3- utrs of ldha and fut8 mrnas contained the complementary sequence to seed sites of mir-34a , implying that ldha and fut8 were targets of mir-34a. 25181679_2 validation of these targets was further carried out by qpcr and western blot analysis , the results of which supported that ldha and fut8 were targets of mir-34a. 25181679_3 using luciferase activity assay, qpcr, and western blot analysis, we confirmed that ldha and fut8 were down-regulated by mir-34a. 26725775_2 mirna-149* mimics downregulated junb levels in molt-4 and jurkat cells, while mirna-149* inhibitors dramatically upregulated junb expression in these cells. 26725775_3 these data suggest that junb is a target for mirna-149*. 26725775_4 these findings confirmed that mirna-149* negatively regulates junb expression in t-all cell lines. 22526161_1 in mpnst cells, transfection of mir-21 inhibitor significantly increased caspase activity , significantly suppressed cell growth , and upregulated protein level of pdcd4, indicating that mir-21 inhibitor could induce cell apoptosis of mpnst cells. 22623155_2 bcl-2 and sirt1 as the targets of mir-34a were found to be in reverse correlation with ectopic expression of mir-34a. 22983984_1 in vitro assays showed that mtor is a direct target of mir-144, and downregulation of mir-144 facilitated proliferation of crc cell line, ht29. 22983984_2 mtor signaling is frequently dysregulated in a variety of human cancers, and in silico analysis has revealed two mir-144 binding sites in the mtor 3'utr. in this study, in silico analysis found two mir-144 binding sites in the 3'utr of mtor with perfect matches at microrna positions 2-8 and 1-7 . 26602079_1 compared to mir-302c, mir-520e cannot promote viral replication and production, although the two micrornas target the same site of the nik 3 ' utr. 26602079_2 together, these results demonstrate that, among members of the mir-302 family, mir-302c plays a key role in nik expression. 26602079_3 these results suggest that mir-302c inhibits nik expression and its downstream signaling pathway. 26602079_4 further, our studies show that mir-302c inhibited nik expression and prevented nf- j b translocation to the nucleus by targeting nik, resulting in a reduction in ifnb expression . 17707831_1 mir-15a and mir-16-1, both micrornas negatively regulate bcl2 at a post-transcriptional level and bcl2 repression induces apoptosis in meg-01 chronic leukemia cell line and reduced in-vivo tumorigenicity. 26677864_1 rna sequencing analysis and additional in vivo assays showed that mir-21 inhibits apoptosis of cystepithelial cells, likely through direct repression of its target gene programmed cell death 4. next, we identified a direct mir-21 target that may be relevant to apoptosis and kidney cyst growth. 26677864_3 thus, it is possible that mir-21 promotes cyst growth through direct repression of pdcd4. 26677864_4 taken together, these results suggest that mir-21 promotes cyst growth, at least in part, through direct repression of pdcd4 in cyst epithelial cells. 26238203_1 these changes of firefly luciferase translation indicated that mir-506 targets the 3'utr of pim3. 26238203_2 this result indicated that mir-506 may suppress pim3 expression through binding to the seed sequence at the 3'utr of pim3. 26238203_3 these results indicated that mir-506 repressed endogenous pim3 expression in pc cells by directly targeting the pim3 3'utr, and pim3 is a target gene of mir-506. 23492770_1 furthermore, the role of mir-17 was because of its target gene tcf3 , a key transcription factor of canonical wnt pathway. 23492770_2 furthermore, we identified that the key transcriptional factor of canonical wnt pathway, tcf3, was a direct target gene of mir-17. 23492770_3 accordingly, these data demonstrated that tcf3 is a direct target gene of mir-17. 23492770_4 to elucidate the further functional link between mir-17 and canonical wnt signaling, we found that tcf3, a key transcription factor of canonical wnt pathway, was the direct target gene of mir-17. 26279428_1 moreover, mir-100 was found to bind to the 3'-utr of fgfr3 mrna to prevent its translation. 26279428_2 these data suggest that mir-100 targets 3'-utr of fgfr3 to inhibit its translation. 26279428_3 these data suggest that the translation of fgfr3 in disc cells may be regulated by mir-100. 26279428_4 moreover, this hypothesis was proved by luciferase reporter assay, in which we identified a binding site of mir-100 at 3'-utr on fgfr3 mrna, which is 26231038_1 according to the bioinformatics database , mir-186 might bind to xiap and pak7 3'-utr region. 26231038_2 the predicted mir-186 binding sites in the 3'-utr region of xiap or pak7 and the designed mutant sequence were indicated. 25869073_1 we further determined whether mir-451 regulates lrh-1 expression in human osteosarcoma cells. 25869073_2 mrna and protein expressions of lrh-1 were detected in mir-451 mimic-transfected cells. 25869073_3 the mrna expression level of lrh-1 was significantly decreased by mir-451 mimics . 25869073_4 western blot analysis results showed that the protein expression level of lrh-1 was also downregulated by mir-451 mimics . 22463747_1 our data suggest that mir-15a/16-1 can also modulate the bcl2 gene expression in cd4 t cells from rr-ms patients, thereby affecting apoptosis processes. 26549736_2 as an downstream molecule in cd28 costimulatory signaling pathway, arrb2 plays an important role in t cell activation through interacting with pde4 . in addition, mir-150 is highly complementary with the 3'-utr of the arrb2. 26549736_3 we decided to determine whether arrb2 is regulated by mir-150. 26549736_4 overexpression of mir-150 significantly repressed fluorescence activity controlled by the wild type 3'-utr of arrb2.but the activity was not affected by the mutant 3'-utr of arrb2 although the transfection efficiency was about the same in different transfections . 26549736_5 these data collectively demonstrated that arrb2 is downregulated by mir-150 in human cd4+ tlymphocytes. 26103953_1 moreover, bioinformatic prediction suggested that cxcl12 was a target gene of mir-448. 26103953_2 we also demonstrated that restored expression of cxcl12 dampened mir-448-mediated suppression of tumor progression, which suggests the important role of mir-448 in tumor progression. 26103953_3 above data showed that cxcl12 was the target gene of mir-448, we want to know whether mir-448 regulates proliferation in ovarian cancer growth with overexpression of cxcl12. 26103953_4 the data showed that mir-448 in skov3 and a2780 cells inhibited proliferation of the cells with cxcl12 overexpression . 26681033_1 western blotting results revealed that pfkfb3 protein expression decreased in saos-2 cells after transfection with mir-26b. 26061281_1 the overexpression or knockdown of mir-135b did not affect the mrna stability of tgfbr2 . 26061281_2 these results demonstrated that mir-135b specifically regulates tgfbr2 expression at the post-transcriptional level, which is the most common mechanism of animal mirna action. 26061281_3 in conclusion, our results demonstrated that mir-135b directly binds to the 3'-utr of the tgfbr2 mrna transcript to suppress tgfbr2 expression in crc cells. 20651244_1 let-7a, let-7b and let-7f can all specifically interact with the prdm1 3'utr and down regulate gene expression. 20651244_4 thus, these results indicate that let-7a, let-7b and let-7f can all specifically interact with the prdm1 3'-utr and down-regulate gene expression. 20651244_5 these results indicate that let-7 can also targetendogenous prdm1 in dlbcl cells. 23028144_1 mir-26a targets the transcription factors smad1 and smad4, critical for the tgf-b/bmp pathway, and expression of microrna-resistant forms of these transcription factors inhibits differentiation. 23028144_2 in vitro cell culture and animal studies establish that mir-26a plays an important role in promoting muscle differentiation and regeneration by down-regulating the critical transcription factors of the tgf-b/bmp signaling pathway, smad1 and smad4, by directly targeting their 3' untranslated regions . in similar experiments, both of the predicted target sites in the smad4 3' utr were also found to be true target sites for mir-26a . 23028144_3 these results demonstrate that 3' utrs containing the mir-26a target sites are essential for the down-regulation of smad1 and smad4 proteins and for optimal differentiation of myoblasts. 23028144_4 we demonstrated that mir-26a regulates a well-known repressor of myogenesis, the tgf--beta/bmp signaling pathway, by directly targeting the 3' utrs of smad1 and smad4, the genes encoding critical transcription factors of this pathway . 23136997_2 our results indicate that only unedited pri-mir-376 rnas were present in the cochlea suggesting that prps1 levels and activity in the inner ear may not be regulated through the editing of mir-376. 26746014_1 a search of the 3'-utr of the human rhog gene revealed two evolutionarily highly conserved and two poorly conserved mir-124 target sequences . 26576539_1 ror1 is a direct downstream target of mir-27b-3p. 26576539_2 notably, by analyzing of their expression levels in gc tissues, the expression level of mir-27b-3p was found to be negatively associated with ror1 mrna expression 25574238_1 furthermore, a novel target of mir-148a was found, sphingosine-1-phosphate receptor 1 , whose expression was negatively regulated by mir-148a at a post-transcriptional level in hepatocellular carcinoma hepg2 cells. 25574238_2 accordingly, the current study suggests that mir-148a plays an inhibitory role in the regulation of hepatocellular carcinoma cell invasion by directly targeting s1pr1. 25574238_4 2b, the luciferase activity was significantly reduced in hepg2 cells co-transfected with the wild-type 3'-utr of s1pr1 and mir-148a mimics, but unchanged in hepg2 cells co-transfected with the mutant s1pr1 3 utr and mir-148a mimics, indicating that mir-148a directly binds to the 3'-utr of s1pr1 in hepg2 cells. 25574238_5 further investigation identified s1pr1 as a direct target of mir-148a, and the protein expression of s1pr1 was negatively regulated by mir-148a in hepatocellular carcinoma cells. 23748240_1 these findings demonstrate that mir-143 directly targets igf-ir and irs1. 23748240_2 mir-143 targets both igf-ir and irs1 in beas-2b cells. 23748240_3 more importantly, we validated that both igf-ir and irs1 are the functional targets of mir-143. 21224400_1 western blot analyses revealed that mir-376c, but not mir-22, decreased alk7 protein levels. 21224400_2 however, mrna levels of alk7 were not affected by mir-376c . 21224400_3 by contrast, anti-mir-376c increased alk7 protein levels . 21224400_4 mutation of the mir-376c targetsites at the alk7 3'-utr significantly reduced the inhibitory effect of mir-376c on luciferase activity . 21224400_5 furthermore, inhibition of endogenous mir-376c by anti-mir-376c phenocopied the effect of alk7 overexpression and decreased the size of spheroids . 23548270_1 mechanistic analyses identified sox9 and adam17 as two novel mir145 targets relevant to this process. 23548270_2 we showed direct targeting by mir145 to the 3' -untranslated region regions of sox9 and adam17 in hnc-tics, and further showed a direct interaction between sox9 and adam17-promoter by chip assay. 23548270_3 collectively, our results show how mir-145 targets the sox9/adam17 axis to regulate tic properties in hnc, and how altering this pathway may partly explain the anticancer effects of curcumin. 22733824_1 therefore, endogenous mir-153 inhibits expression of app in human neurons by specifically interacting with the app 3'-utr. 22733824_2 figure 2.mir-153 inhibits expression of endogenous app mrna and protein. 22733824_3 these data demonstrate that app and mir-153 exhibit inverse expression patterns across time in hfb culture and suggest that the inhibitory relationship between mir-153 and app could underlie these patterns. 22733824_4 therefore, we were able to successfully transfect these primary human neuronal cells and demonstrate down-regulation of app following mir-153 delivery. 22733824_5 therefore, endogenous mir-153 actively inhibits app expression in human neurons under physiological culture conditions. 22733824_6 this confirms that mir-153 can also regulate a-beta levels, presumably via its activity against app. 26379276_1 this data confirms that a specific binding site sequence interaction is required for mir-200a mediated regulation of acot7. 26379276_4 fig 4. acot7 is a direct target of mirna-200a. 23873911_3 sgrs allele with g176c and g178c mutations ,repressed manx′-′lacz almost as efficiently as wild-type sgrs but no longer regulated the activities of ptsg′-′lacz or yigl′-′lacz . 19883630_1 mir-326 was downregulated in a panel of advanced breast cancer tissues and consistent reversely with expression levels of mrp-1. 19883630_3 3c shows that expression levels of mir-326 mrna correspond negatively with mrp-1 mrna in tissues . 19883630_4 to examine whether mir-326 directly target mrp-1, a segment of mrp-1 3'-utr containing mir-326 binding sites was cloned into a luciferase reporter system. 19883630_5 mir-326 downregulated expression of mrp-1. 21444814_1 mir-138 inhibits ptk2 gene expression by binding to the predicted targetsite in the 3' utr. 21444814_2 qrt-pcr analysis revealed that expression of protein tyrosine kinase 2 , the gene encoding fak, was increased during osteoblast differentiation of hmsc-tert and in primary hmscs , similar to osteoblast marker genes and coinciding with down-regulation of mir-138 . in comparison, premir-138 had no effect on the luciferase control reporter without the ptk2 3- utr, implying that ptk2 is a direct target of mir-138. 21444814_3 accordingly, phosphorylation of runx2 and expression of osx, a downstream targetgene of the erk1/2 pathway , were decreased when mir-138 was overexpressed and increased in the absence of mir-138 , supporting that mir-138 suppresses fak downstream signaling by negatively regulating fak at the posttranscriptional level. 19503096_1 to further confirm targetspecificity between mir- 512-5p and its potential target mcl-1, we carried out luciferase reporter assay with a vector containing the putative mcl-1 3' untranslated region targetsite downstream of the luciferase reporter gene, which was transfected into ags cells. 19503096_2 these data suggest that mcl-1 is one of the target of mir-512-5p and that activation of mir-512-5p induces suppression of mcl-1, resulting in apoptosis of gastric cancer cells. 19859982_1 mir-214 negatively regulates mek3 and jnk1 through binding to their 3'utrs by assay of gfp expression . 19859982_2 to further demonstrate that mek3 and jnk1 are negatively regulated by mir-214, stable cell lines overexpressing mir-214 or psilencer/nc were developed. 19859982_4 the results also show there is significantly lower expression of mek3 and jnk1 atboth the mrna and protein level in cells that overexpress mir-214 compared with the negative control cells . 17178851_1 tcl1 expression in cll is, at least in part, regulated by mir-29 and mir-181. 17178851_2 mir-29 and mir-181 targettcl1. in summary, for samples with high mir-29b and/or mir-181b expression, 17 of 20 showed low or medium tcl1 expression . in addition, none of the samples with high mir-29b and/or mir-181b expression showed high tcl1 expression . 17178851_3 these results suggest that tcl1 expression in b-cll is, at least in part, regulated by mir-29 and mir-181. in this report, we show that tcl1 expression is regulated by mir-29 and mir-181 and this regulation is relevant to the three groups of b-cll we studied. 17178851_4 although we observed a reverse correlation between tcl1 protein expression and these two mirs, a significant proportion of b-cll samples show low tcl1 expression and low expression of mir-29 and mir-181 . 26667302_1 mir-34a targets the 3'utr of axl mrna and inhibits its expression. 26667302_3 these findings implicate that, in contrast to mir-34a, mir-34c may regulate axl expression through an indirect mechanism, probably by targeting other molecules that modulate axl promoter activity. 20023705_2 finally, western blot detected a reduced level of the endogenous cdc42 by mir-224 compared to vector control, further supporting a suppressive role of mir-224 in cdc42 . 26385772_1 luciferase reporter assay further identified that a proliferation-inducing ligand , a member in the tumor necrosis factor superfamily, was a novel target gene for mir-383. 26385772_2 subsequent investigation revealed that mir-383 expression was inversely correlated with april messenger rna expression in hcc tissues. 26385772_3 collectively, our data indicated that mir-383 could directly target april in hcc cells by interaction with its 3'-utr binding site, thereby regulating endogenous april expression at both transcriptional and translational levels. 18434550_2 we found that mir-29a , mir-29b-1 , and mir-9 affected significantly luciferase expression , whereas mir-15a, -19b, and -124a showed no effect in this assay. 18434550_3 we could confirm that mir-29a and -29b-1 showed coregulated expression with bace1 in brain development and ad , whereas we did not find such correlation for mir-9//we confirmed these results in human neuroblastoma sk-n-sh cells, demonstrating that mir-29a/b-1 could suppress endogenous bace1 expression by ~50% upon transient transfection . 18434550_5 we show here that mir-29a, -29b-1, and -9 can regulate bace1 expression in vitro. 18434550_6 the mir-29a/b-1 cluster was significantly decreased in ad patients displaying abnormally high bace1 protein. 18434550_7 mir-29a and -29b-1 can down-regulate endogenous bace1 upon transient overexpression 20956612_1 in the present report, we identified genes that are molecular targets of mir-146b, mir-208a, and mir-219, which display key roles in inflammation and the immune response . 20956612_3 8, overexpression of mir-146b resulted in significant down-regulation of transcripts of several cytokines, chemokines, and their receptors, such as interleukin -8 and il-10, il-12 receptor -beta2, chemokine cc motif receptor 3 , interferon alpha1 and ifn-beta1, and members of il-1 family. 20956612_4 also, genes involved in the innate immune response and pathogen recognition, i.e., s100a12, lps binding protein , c-reactive protein, complement component 8 alpha polypeptide , toll-like receptor 9 and 10, and peptidoglycan recognition protein 1 and 2, were significantly reduced in m桅-mir-146b. 20956612_5 in addition, we found reductions in the mrnas for conserved helix-loop-helix ubiquitous kinase , also known as i魏b kinase alpha, tumor necrosis factor receptor-associated factor 6 , nitric oxide synthase 2, platelet-activating factor receptor , and cd40 . in mir-208a-overexpressing m桅s, reductions were obtained for mrnas encoding for cd14, cd40 ligand , prostacyclin i2 receptor , thromboxane a2 receptor , and programmed cell death 4 , a tumor suppressor molecule that regulates nf-κb activation and decreases il-10 production . 20956612_7 mir-219 overexpression gave significant reduction in cd14, tnf receptor ii, phospholipase c纬2, and arachidonate 5-lipoxygenase , as well as leukotriene production . 12410838_1 clones carrying rpra increased the translation of rpos. the rpra gene encodes a 106 nucleotide regulatory rna. 12410838_2 at least two small rnas, dsra and rpra, participate in the positive regulation of rpos translation. 12410838_3 unlike dsra, rpra does not have an extensive region of complementarity to the rpos leader, leaving its mechanism of action unclear. 12410838_5 mutations in the gene interfere with the induction of rpos after osmotic shock when dsra is absent, demonstrating a physiological role for rpra. 26512644_1 meis2 is identified as the target of mir-134. 26512644_2 collectively, meis2 is the direct and specific target gene of mir-134. 26512644_3 these data suggest that mir-134 regulates hcmpcs proliferation by targeting meis2. 16564011_3 to investigate the possibility that mir-372 and mir-373 suppress the expression of lats2, we performed immunoblot analysis of cells expressing wt and mutant mir-372&3, the cluster and the controls p53kd and empty vector. 16564011_4 both in the absence of rasv12 and in its presence, a significant reduction in lats2 protein level was observed upon mir-372&3 expression . 16564011_5 using quantitative rt-pcr and immunoblot analysis, we observed a 2-fold effect on lats2 rna levels and 4- to 5-fold on protein levels by the mir-371-3 cluster . 16564011_7 these results show that a combined effect of rna destruction and translation inhibition is used by mir-372&3 to silence lats2. 26392416_1 these results suggest that mir-200c can directly target kras. 26392416_2 these results provide evidence that mir-200c directly recognizes the 3'-utr of kras mrna and inhibits kras translation. 26392416_3 these results suggest that mir-200c inhibits the akt and erk pathways by targeting kras. 26396670_2 the luciferase activity of pmir-sox4-3'-utr-wt construct was significantly decreased upon the over-expression of mir-133a in te13 cells, whereas its mutant counterpart was not . 26396670_3 in addition, the protein level of sox4 in te13 and kyse150 cells was dramatically reduced by mir-133a . 26396670_4 taken together, these data indicated that sox4 is a direct target of mir-133a at least in esophageal cancer. 26396670_5 these data indicate that mir-133a directly inhibits sox4 expression via targeting its 3'-utr and induces emt of escc cells. 22843060_3 results showed that the expression levels of mirna-146a were positively correlated with that of lmp1 protein expression. 18006822_1 introduction of the mirnas let-7c, mir-10a, mir-144, mir-150, mir-155, and mir-193 also affected the activation of the caspase cascade. 26839366_1 in contrast, renal expression of ras gtpase-activating protein sh3 domain-binding protein 2 , a putative mir-23b target, increased in dn. in vitro, overexpression of mir-23b decreased, and inhibition of mir-23b increased, g3bp2 expression levels. 26839366_2 these data identified mir-23b binding to the 3'-utr of its putative target g3bp2 mrna. 20816946_1 akt1, cyclind1, mmp-2, mmp-9 and bcl-2 protein expression decreased, and p27 expression increased in a dose-dependent manner with mir-451 mimics oligonucleotides. 22628407_1 we computationally and experimentally validated that metastasis suppressor 1 is a direct mir-23a target and similarly validated that the ubiquitin ligase fbxw7 is a direct mir-27a target. 22628407_2 similarly, we show that metastasis suppressor 1 is a direct mir-23a target; mtss1 interacts directly with cortactin to promote fi lopodia formation and upregulates src signaling . 22628407_3 functionally, our studies show that mtss1 is an important direct target for mir-23a and that reduced mtss1 levels accelerate mechanisms that promote colorectal cancer migration. 26173501_1 fscn1 was identified as a direct target of mir-145 and mir-133a. 26173501_2 mir-145 and mir-133a directly target fscn1. 26173501_3 mir-145 and mir-133a negatively regulated the protein expression of fscn1 in hcc cells 26537584_2 furthermore, our results showed that mir-100 directly inhibited the expression of fzd-8 and inactivated the wnt/-beta-catenin pathway in breast cancer cells. 26537584_3 ourfindings suggested that fzd-8 was a direct target of mir-100. in our studies, we found that mir-100 inhibited the migration and invasion of breast cancer cells by targeting fzd-8 and inhibiting the wnt/-beta-catenin signaling pathway. 22785209_1 from the above results, cx43 is one of the target genes of mir-20a and is repressed by mir-20a 26151111_1 to determine whether mir-133b directly targets egfr in crc cells, a luciferase assay was performed. 26151111_3 the results showed that mir- 133b significantly suppressed the luciferase activity of the reporter gene, containing the 3'utr of egfr compared with the controls. 26151111_4 rt-qpcr analysis demonstrated that an sincreased expression of mir- 133b significantly decreased the mrna expression levels of egfr compared with the cells transfected with the control . 26151111_5 taken together, these results confirmed that mir- 133b directly targeted egfr and repressed its expression levels in crc cells. 26409449_1 further study revealed that mir-218, which was underexpressed in lung carcinoma, was predicted to bind the 3'-untranslated region of mef2d mrna. 26409449_2 mir-218 was shown to suppress the activity of luciferase with mef2d 3'-utr. 26409449_3 the changes in mir-218 levels affected the expression of mef2d in lung cancer cells and normal fibroblast cells. 26409449_4 there is also an inverse association between mir-218 abundance and mef2d levels in the lung carcinoma specimen. 26409449_5 the above findings indicated that mef2d is an authentic target of tumor suppressor mir-218. 1702997_1 micf binds to 5'-utr of the ompf transcript and represses production of ompf in response to environmental and/or stress conditions. 1702997_2 approximately one-third of the micf rna sequence participates in micf rna/ompf rna duplex formation and shields the shine-dalgarno sequence and aug translation start site on the message. 23229340_1 microrna-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in hct116 colon cancer cells.results of the present study pertaining to the role of mir-18a in regulating autophagy and atm gene expression in colon cancer cells revealed a novel function for mir-18a in a critical cellular event and on a crucial gene with significant impacts in cancer development, progression, treatment and in other diseases. 25954907_1 a database search revealed the predicted mirnas that target the catalytic subunit of the telomerase enzyme tert . 25954907_2 among the 6 mirnas identified from the database search, 5-namely, mir-138, mir-491-5p, mir-3687, mir1207-5p, and mir-3065-3p howed differential expression in our study. 25954907_3 only 2 of these, mir-3687 and mir-1207-5p , were changed by at least 2-fold. 21224353_2 in the selected 12 hg-psc tissues with hmga2 overexpression, significant downregulation of mir-29b expression was evident compared with expression in matched normal ovarian tissues . 21224353_3 a significant inverse correlation of hmga2 and mir-29b expression was noted . 25155445_1 mir-33a precursors significantly decreased smad7 mrna and protein expression when compared to their expression in cells transfected with the negative control mirna precursors. 25155445_2 mir-33a inhibitor transfection significantly increased smad7 mrna and protein expression when compared with cells transfected with the negative-control mirna inhibitors. 25155445_3 these results suggest that mir-33a targets smad7 to regulate tgf-b1 signaling pathway downstream targets. 25155445_4 all these data suggest that mir-33a directly targets smad7 in lx-2 cells. 23353875_1 to further confirm whether mir-433 directly regulates runx2 transcript, we made pmirglo-s1, -s2 and -s3 reporter constructs,containing a putative binding site of mir-433 of runx2- 3'-utr separately, as mentioned in 'materials and methods' . 23353875_2 these results revealed that s1 and s2 sites on the 3'-utr of runx2 may be a direct target of mir-433. 23071539_1 the mtt test showed inhibition of a549 cell proliferation and annexin v-fitc/pi dual staining showed increased apoptosis in the mir-511- and mir-1297-treated cells compared to the nc cultures. 23071539_2 a transcription factor downstream of trib2, the ccaat/enhancer-binding protein alpha , was expression at higher levels after mir-511 decreasing trib2 expression. 24488097_1 we further identified the two bh3-only proteins noxa and bmf as new mir-197 targets responsible for induction of apoptosis in p53 wild-type cells, delineating mir-197 as a key survival factor in nsclc. 20452491_1 luciferase assays and cyr61 transfection assays experimentally validated that mir-155 efficiently target the 3' untranslated region of cyr61. 20452491_2 these findings suggest an inverse relationship between mir-155 and cyr61 expression, and an increased mir-155 expression associated with the down-regulation of cyr61 in pe placenta. 20452491_3 interestingly, qrt-pcr analysis of messenger rna from these cells showed that cyr61 mrna level was also influenced by mir-155 , indicating that mir-155 also affects cyr61 at the mrna level.these 20452491_4 results imply that the sequence ofcyr61 3'-utr is a target of mir-155 and that mir-155 down-regulates cyr61 by targeting the 3'-utr sequence. 22207524_1 k-ras and bcl-2 were identified as direct target of mir-181d and were up-regulated in glioma samples. 22207524_2 immunohistochemical staining revealed a down-regulation in k-ras and bcl-2 levels in the mir-181d group , confirming the in vitro data that k-ras and bcl-2 as direct target of mir -181d. in summary, our results show for the first time that mir-181d is frequently down-regulated in glioma and may be a potential tumor suppressor in glioma by targeting k-ras and bcl-2. 26563755_1 we identified mir-125a as a direct regulator of il-6r, and the genotype of rs12976445 might be a novel predictor of the development of dn in dm. in this study, we confirmed the differential expression of il-6r in dn and identified mir-125a as a regulator of il-6r. 26563755_2 our results showed that mir-125a is a key player in the development of dn via targeting il-6r, and underexpression of mir-125a promoted proliferation of mesangial cells by releasing the inhibition on il-6r. 25387077_1 peroxisome proliferator-activated receptor gamma was inversely correlated with mir-130b expression in hcc tissues. in addition, down-regulation of mir-130b restored ppar-纬 expression and subsequently suppressed epithelial-mesenchymal transition in hcc cells. 25387077_2 we identified ppar纬 as a direct target of mir-130b in hcc in vitro. 25387077_3 notably, ppar-纬 knockdown abolished down-regulation of mir-130b-inhibited emt in mhcc97h cells. in conclusion, mir-130b may promote hcc cell migration and invasion by inhibiting ppar-纬 and subsequently inducing emt. 25387077_4 taken together, these data indicate that mir-130b directly suppresses ppar纬 expression that subsequently promotes emt progression in hcc. 26390028_1 of these mirnas, we found mir-195 directly targeted 3'-untranslated region of tert gene by computational target prediction analysis and luciferase assay, and knockdown of mir-195 significantly increased tert expression in omscs. 26390028_2 these results demonstrated that tert is a direct target of mir-195 in stem cell aging. 25999017_2 moreover, the enhanced mir-130a expression in epcs significantly repressed map3k12 protein expression compared with the mir-control group . 25999017_3 we also overexpressed the map3k12 or downregulated mir-130a in diabetic epcs to further increase the map3k12 protein level in diabetic epcs . 20737563_5 the induction of in vitro transcription and enrichment of markers for transcriptionally active promoters in the il24 and il32 genes was observed in response to mir-205. 22002058_1 although most of the repressed mrnas appear to be indirect target because they lack specific seeding sites for mir-346, we demonstrate that the human tap1 mrna is a direct target of mir-346. 22002058_2 these results support the hypothesis that mir-346 is a direct post-transcriptional regulator of human tap1 expression during er stress. 22002058_3 here, we concentrated on the direct role of mir-346 in the post-transcriptional regulation of human tap1. 22002058_4 these results indicate that the mir-346 antagomir protected the human tap1 mrna from mir-346 during er stress. 22002058_5 together, these data support a direct effect of mir-346 in the post-transcriptional regulation of human tap1 expression. 24650454_1 overexpression of mirna-21 could significantly enhance proliferation and invasion and inhibit the apoptosis of tpc-1 cells. in addition, mirna-21 and pdcd4 expression showed a significantly negative correlation in tpc-1 cells. 20049172_2 reciprocal repression of mir-200c and zeb1 occurs in some but not all cell types. 20049172_3 directly increasing mir-200c levels in hey cells by transfection of a mir-200c mimic results in repression of zeb1 expression . 22952654_1 using reporter assays, we established that mir-29a target the 3' untranslated regions of vdac1 and vdac2. 22952654_2 our study adds vdac1 to this list of mir-29a apoptosis target, thus suggesting a coordinated regulation of these proteins by mir-29a during apoptosis. 22952654_3 in summary, using mirna proteomics, we not only studied the effect of two apoptosis related mirnas but also show that the mitochondrial outer membrane porin component, vdac can be targeted by mir-29a. 22952654_4 we also showed downregulation of vdac1 at the protein level after over-expression of mir-29a by western blotting . 22161761_1 enforced expression of mir-34a* led to an increased rate of fasl- and trail-mediated apoptosis in rasfs. 22161761_3 finally, we identified xiap as a direct target of mir-34a*. 26143754_1 mir-363 directly targets mcl-1 and inhibits its expression in hepg2-r cells. 26143754_2 the putative mir-363 target sites in mcl-1 mrna 3'-utr are as follows: gugcaau, position at 12- 18 nucleotides of mcl-1 mrna 3'-utr . 26722475_1 luciferase fluorescence report assay demonstrated overexpression of mir-140-3p could reduce the intensity of fluorescence in a549 and h1299 cells transfected with the atp6ap2 3'-utr vector, while had no effect on the atp6ap2 3'-utr mutant vector. 26722475_2 d. the protein level of atp6ap2 was regulated by mir-140-3p in a549 and h1299 cell lines with gapdh as a loading control. 26722475_3 mir-140-3p suppressed atp6ap2 expression by about 80% on both lung cancer cell lines. 26722475_4 overall, these results indicate that mir-140-3p suppresses atp6ap2 expression by directly binding to its 3'-utr. 23418360_1 we examined the levels of these proteins in 4t1 and mt-1 cells stably transfected with mir-24. in both cell lines, mir-24 expression resulted in decreased levels of ptpn9 and ptprf . 23418360_3 consistent with this, transfection with anti-mir-24 increased ptpn9 and ptpfr levels . 26796271_2 bioinformatics methods were used to predict that ppp2r2c, a pp2a substrate-binding regulatory subunit, containing binding sites for mir-572. 26796271_3 overexpression mir-572 significantly suppressed ppp2r2c protein levels, while mir-572-in markedly promoted ppp2r2c protein expression in es-2 cells. 26796271_4 to further investigate the relationship between mir-572 and ppp2r2c, we cloned the wild-type t 3'utr of ppp2r2c mrna that included the binding site of mir-572 into pmir-report vector . 26796271_5 these results demonstrated that mir-572 could regulate ppp2r2c expression via direct targeting its 3'utr. 25603050_2 the results of a luciferase reporter assay showed that mir-204-5p can directly bind to the 3' untranslated region of insulin-like growth factor-binding protein 5 mrna, and igfbp5 overexpression partially reversed the growth-inhibitory effects of mir-204-5p. 25603050_3 these results indicate that mir-204-5p acts as a tumor suppressor in ptc by regulating igfbp5 expression and that mir-204-5p can potentially serve as an antitumorigenic agent in the treatment of ptc. 23395552_1 previous studies indicate that mir-21 increases the synthesis of ifn--gamma and il-17a by t cells and suppresses apoptosis via programmed cell death protein 4 26460070_1 herein, we show plgf treatment of endothelial cells reduced levels of mir-301a and mir-454 from basal levels. 26460070_3 our studies showed that mir-301a and mir-454, target the 3'-utrs of et-1 and pai-1 mrnas. 26460070_4 these data showed that both mir-301a and mir-454 target the 3'-utr of et-1 mrna to attenuate et-1 synthesis. 26460070_5 the specificity of the interaction between mir-301a and mir-454 and their respective mirna recognition elements in the 3'-utr of et-1 mrna was established by inclusion of the et-1 3'-utr in a luciferase translation reporter. 22483937_1 mir-34a inhibits lipopolysaccharide-induced inflammatory response through targeting notch1 in murinemacrophages. 22483937_2 bioinformatics predictions revealed a potential binding site of mir-34a in 3' untranslated region of notch1 and it was further confirmed by luciferase assay. 22483937_3 as a result, mir-34a obviously repressed the activity of luciferase fused to notch1 3'utr , which indicated a direct interaction between mir-34a and notch1 in macrophages. 22483937_4 thus, we can conclude from these results that the suppressive effect of mir-34a in inflammation is conducted partially through targeting notch1. 26276504_3 pdcd4 is an apoptosisrelated protein that has a potential binding region in the 3'-utr completely complementary to the seed region of mir-202. 26276504_4 we confirmed that mir-202 decreased pdcd4 in osteosarcoma cells u2os at both mrna and protein levels . in contrast, knockdown of pdcd4 increased pdcd4 in osteosarcoma cells u2os at both mrna and protein levels. 26276504_5 the cleavage parp induced by doxorubicin is higher in u2os cells cotransfected with mir-202 mimics and pdcd4 overexpression than in cells transfected with mir-202 mimics. 26276504_6 the data demonstrate that the role of mir-202 in chemoresistance by inhibiting apoptosis induced by doxorubicin is mediated by pdcd4. 26629004_1 these results indicated that prkcd is the target of mir-181c. 26739063_1 interestingly, mir-34a and mir-182 directly bind to the 3'utr of lmtk3 mrna and consequently inhibit both its stability and translation, acting as tumour suppressor-like mirnas. 26739063_2 two of the identified mirnas, namely mir-34a and mir-182, act as tumour suppressors by directly targeting lmtk3-mrna and inhibiting cell proliferation, invasion and migration in breast cancer cell lines overexpressing lmtk3. 26739063_3 this result indicates that mir-182 and mir-34a directly bind to the 3'utr of lmtk3 and suppress its activity 26648284_1 we identified p21 as a target gene of mir-512-5p. 26648284_2 further evidence showed that p21 was the target of mir- 512-5p, whose downregulation may be responsible for the function of mir-512-5p. 26648284_3 collectively, these results indicated that mir-512-5p could bind to p21 3'-utr to repress p21 expression. 26648284_4 to illuminate the effect of mir-512-5p in nsclc cells, we identified that p21 is a new target of mir-512-5p. 21890460_1 further studies revealed that p21cip1/waf1 is a downstream target of mir-423 in hcc cells, as mir-423 bound directly to its 3' untranslated region and reduced both the messenger rna and protein levels of p21cip1/waf1. 21890460_2 the results showed that mir-423 decreased the relative luciferase activity with the wild-type 3' utr of p21cip1/waf1. 21890460_3 in particular, mir-423-3p, but not mir-423-5p, contributed to this effect . 21890460_4 furthermore, inhibition of mir-423-3p, but not mir-423-5p, increased significantly the expression levels of p21cip1/waf1 protein and mrna in snu-449 cells . 21890460_5 taken together, these results suggest that mir-423 can downregulate p21cip1/waf1 expression by directly targeting its 3' utr. 21890460_6 these findings indicate that p21cip1/waf1 is a bona fide target of mir-423 in hcc cells. 25550801_4 n-cadherin and vimentin were up-regulated significantly when mir-451 was inhibited in mir-451 inhibitor group, however, no significant changes in mimics group. 21609763_1 furthermore, we identified a functional mirna site for hsa-mir-608 within the col5a1 3'-utr and using deletion constructs we have identified additional elements which regulate col5a1 mrna stability. 21609763_3 functional analysis of the putative mirna binding site for hsa-mir-608 within the col5a1 3'-utr in ht1080 cells. 21609763_4 to test whether the polymorphic putative hsa-mir-608 binding site is functional, several reporter constructs containing the full length col5a1-3'-utr were transfected with mirna mimic for hsa-mir-608 and assayed for luciferase activity. 21565331_1 we examined whether bace1 mrna levels were affected by mir-29c overexpression or knockdown. 21565331_2 the results demonstrated that bace1 mrna levels were unchanged, indicating that mir-29c blocks bace1 protein translation but that it does not promote degradation of bace1 mrna . 21565331_3 these results indicate that mir-29c directly regulates bace1 by binding to the first predicted target site in the 3'-utr of bace1. 21565331_4 the results revealed that decreased bace1 protein generated less peptide compared with controls by influencing on app processing in the mir-29c mice vivo. 23335975_2 in turn, we have identified neurofibromin 1 as a target of mir-193b, which drives hnscc progression via erk activation. in this current study, we identified nf1 as one target for mir-193b. 23359619_1 moreover, the luciferase reporter assay was useful to confirm the occurrence of mirna-mrna interactions within the cellular milieu focusing on rorc and cd8a mrnas targets. 23359619_2 we confirmed that mir-30b* interacts with rorc mrna and mir-196b interacts with cd8a mrna by hybridization with their respective 3'-utr sequences containing the predicted binding sites for these mirnas. 21829495_2 our interaction analyses indicate that il-1beta could potentially be regulated by mir-211, mir-578, and mir-548d-5p. 26497204_1 the results showed that only ebv-mir-bart10-3p could significantly inhibit btrc expression, rather than other ebv mirnas . 26497204_2 above all, the results suggested that ebv-mir-bart10-3p could inhibit btrc expression in npc cells through binding to the specific sites within the 3'-utr of btrc gene and inhibit its translation. 26051997_1 we measured a significantly lower luminescence signal from 786-o cells co-transfected with the plasmid encoding for the 3' utr of mtor downstream of the luciferase enzyme and mir-199a-3p mimic compared to cells co-transfected with the same plasmid and mirna negative control . 26051997_2 similar results were observed for 786-o cells co-transfected with the plasmid encoding for the 3' utr of met and mir-199a-3p mimic . 26051997_3 using a luciferase reporter assay, we further provide evidence that mir-199a-3p overexpression decreases the expression of met and mtor. 19546886_3 knockdown of mir-21 by specific antisense oligonucleotides inhibited the proliferation potential of hep-2 cells, whereas overexpression of mir-21 elevated growth activity of the cells, as detected by the colony formation assay. the cell number reduction caused by mir-21 inhibition was due to the loss of control of the g1-s phase transition, instead of a noticeable increase in apoptosis. 19546886_6 these findings indicate that aberrant expression of mir-21 may contribute to the malignant phenotype of laryngeal carcinoma by maintaining a low level of btg2. the identification of the oncogenic mir-21 and its target gene, btg2, in laryngeal carcinoma is potentially valuable for cancer diagnosis and therapy. 26527515_2 the strongest negative correlation was demonstrated between rap1a and mir-205-5p, thus suggesting a closer association for this mirna/mrna pair . 26527515_3 subsequent restoration of mir-205-5p expression in a5 and h11 cells,which both present a combination of decreased mir-205/elevated rap1a levels, resulted to rap1a downregulation . 26527515_4 inhibition of mir-205-5p in hras null cell line, which present a combination of increased mir-205/decreased rap1a levels, resulted to rap1a upregulation , thus overall supporting rap1a as a mir-205-5p target. 20164119_1 in contrast, overexpressing mir-29 promoted apoptosis and completely blocked the protective effect of pio. 20164119_2 antagomirs against mir-29a or -29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to ir injury. 20164119_3 western blot analyses demonstrated that mcl-2, an anti-apoptotic bcl-2 family member, was increased by mir-29 inhibition. 22215807_1 here we show that ctdsp2 is a target of mir-26b, a microrna that is encoded in an intron of the ctdsp2 primary transcript. 22215807_2 targetsite predictions revealed the presence of five potential binding sites for mir-26b in the 3'-untranslated region of the zebrafishctdsp2 transcript . the ctdsp2 transcript is thus both host and targetfor mir-26b and object of an intrinsic inhibitory feedback loop . 22215807_3 taken together, our analysis suggests that pre-mir-26b is coexpressed with its ctdsp2 host transcript, but processing to mature mir-26b is inhibited in nscs and nonneuronal tissues. 22215807_4 therefore, the mir-26b-mediated repression of ctdsp2 directly contributes to neuronal differentiation. 22207897_1 moreover, the authors have demonstrated that suppressor of cytokine signaling 3 is a novel target of mir-203, and cisplatin treatment in mir-203 knockdown mcf-7 cells enhanced socs3 expression. 26261179_1 intriguingly, we found that mir-7 indirectly regulated rela activation by targeting the ikappab kinase ikkepsilon. 26261179_2 luciferase reporter assays further demonstrated that mir-7 directly targets the ikbke 3'-utr . in the present study, in addition to the aforementioned findings that rela expression is directly regulated by mir-7, we found that mir-7 fine-tunes rela activation by targeting ikkepsilon. 17504027_1 expression levels of mir-143 and -145 were inversely correlated with cell proliferation of dld-1 cells.persistent 17504027_2 decreased levels of mir-143 in cancer cells may be directly involved in carcinogenesis through activation of the mitogenactivated protein kinase cascade via erk5. 25909817_1 mir-362-5p targets cyld in human nk cells. 25909817_2 to experimentally verify cyld as a target of mir-362-5p in human nk cells, we examined the effect of mir-362-5p overexpression on endogenous cyld expression. 25909817_3 collectively, the above results suggest that mir-362-5p directly targets cyld in human nk cells. 26041383_1 since the expression of mir-21 can be induced by ap1 in response to ras/erk activation , and mir-21 targets the 3'-utr of pdcd4, spry1, spry2, and btg2 to mediate ras-dependent down-regulation of pdcd4, spry1, spry2, and btg2 , we assessed the role of mir-21 in the nnk-mediated ras/erk/ap1 signaling pathway. 26041383_2 it was found that nnk could significantly up-regulate mir-21 but repressed the activity of pdcd4 3'-utr reporter , suggesting that mir-21 might function between ap1 activation and the multiple negative regulators of ras/erk/ap1, pdcd4, spry1, spry2, and btg2. 25829494_1 together these results suggest that cdk5 activity negatively regulates noxa mrna expression, and subsequent protein levels, by positively regulating mir-23a expression. 25829494_2 we recently demonstrated that noxa expression is regulated by the microrna mir-23a . 25026290_1 microrna-100 promotes the autophagy of hepatocellular carcinoma cells by inhibiting the expression of mtor and igf-1r. 23134481_2 over-expression of mir-9 negatively regulates the hes1 protein expression by interacting with the 3'-utr of hes1 mrna, thereby inducing cell cycle exit and neuronal differentiation. 23134481_4 furthermore, knockdown of mir-9 inhibits the oscillatory expression of hes1 mrna in neural stem cells. 23134481_5 these results indicate that mir-9 regulates the proliferation and differentiation of neural stem cells by controlling the dynamics of hes1 expression in the developing brain. 23134481_6 the hes1 protein level was measured after translation was blocked by cycloheximide, but the stability of hes1 protein was not significantly affected by mir-9 . 23134481_7 these results suggest that the stability of hes1 mrna, but not hes1 protein, is negatively regulated by mir-9. 22895815_1 spred-2 was the predicted target of mirna-221 and mirna-485-3p. 22895815_3 a predicted target of mirna-221 and mirna-485-3p, was downregulated in murine asthma models. 26527284_1 mir-148a-3p modulates dnmt1 expression in vitro. 26527284_2 this shows cell-specific expression of mir-14as-3p and also indicates a putative inverse relationship between mir-148a-3p and dnmt1 expression 20628378_1 results showed that both mrna and protein levels of abcg2 were reduced, indicating that it was a target of hsa-mir-520h. 20628378_2 these observations suggested that hsa-mir-520h downregulates abcg2 expression by inhibiting translation or causing mrna instability. 20628378_3 taken together, these data indicate that hsa-mir-520h target abcg2. 20628378_4 taken together, these results suggested that hsa-mir-520h functions as a potent suppressor of panc-1 cell migration and invasion through downregulation of abcg2 expression. 25841337_2 to test the hypothesis that mir-889 regulates cell proliferation by targeting dab2ip, ec109 and ec9706 cells were co-transfected with a mir-889 precursor and a dab2ip-expressing vector. 21170291_2 as seen in figure 6a, there is a perfect match in the seed sequence between mir-21 and complementary nucleosides in the 3'-utr of the mef2c mrna. 21170291_3 our results clearly demonstrate that mef2c is repressed by mir-21, dependent on the seed region, and therefore is a definite targetfor mir-21. 21170291_4 figure 6 mef2c is a target of mir-21. 21170291_5 microrna-21 dysregulates the expression of mef2c in neurons in monkey and human siv/hiv neurological disease. 22139708_1 we also identified e2f3 as a novel target of mir-200b. 22139708_2 luciferase reporters containing the 3' untranslated region sequence of e2f3 messenger rna were used to demonstrate that mir-200b could directly target e2f3. 22771720_1 using bioinformatics analyses, mir-23a is predicted to targetmultiple adult fast myosin heavy chain genes, including myh 1, 2 and 4. luciferase reporter assays show that mir-23a directly target the 3' untranslated regions of these mrnas. 22771720_2 these data suggest that the 3' utrs of the myh1, myh2 and myh4 mrnas are direct target of mir-23a. 22771720_3 taken together with previous reports showing the featured expression of myh1, myh2 and myh4 genes during skeletal muscle development , our results indicates that mir-23a potentially functions in muscle differentiation through regulating myh1, myh2 and myh4 genes. 11900466_3 their expression patterns overlap with that of let-7 rna, suggesting that the lin-41 orthologs could be let-7 targets. 22020560_1 we found that the cholecystokinin-2 receptor gene was a target of mir-148b, and mir-148b might have an effect on cell proliferation by regulating the expression of cck2r which functioned depending on the gastrin in crc. 22020560_3 figure 4. cck2r is a potential target of mir-148b in hct-116 cells. 22020560_4 taken together, our results suggest that cck2r is a potential targetgene in hct-116 cells and cck2r is downregulated by mir-148b only at the translational level. 22020560_5 our results showed that cck2r was negatively regulated directly by mir-148b depending on the seed sequence recognition of 3'-utr in hct-116 cells. 26488467_1 we used bioinformatics analyses to screen all mirnas that target atg6 and altered their levels in endothelial cells in hfd mice. 26488467_2 we found that mir-30 targets 3'-utr of atg6 mrna at one binding site of base pair 97th to 106th . 26488467_4 together, these data suggest that hfd impairs endothelial cell autophagy in apoe mice through suppressing the translation of atg6 mrna by mir-30. 20480266_1 these initial experiments indicate that mir-21 might negatively regulate reck protein. 20480266_2 these results indicate that reck is a direct mir-21 target as expected, lower level of reck protein was found in tumor tissues . 20480266_4 to validate whether mir-21 could regulate reck directly through a putative binding site in mg-63 cells, we cloned reck 3'-utr and its relevant mutant with mutation in the predicted mirna binding site into the downstream of the luciferase gene. 22465665_1 mir-93 directly target pten 3' utr and negatively regulates its expression. 22465665_2 mir-93 plays a critical role in regulating cddp chemosensitivity through suppression of pten expression, and it may serve as a potential targetfor overcoming cddp resistance in human ovarian cancer. 22465665_4 mir-93 inversely correlates with pten expression in cddp-resistant and sensitive human ovarian cancer tissues. 22465665_5 these results suggest that mir-93 may play an important role in regulating cisplatin chemosensitivity directly through adjustment of anti-apoptosis activity by targeting pten in ovarian cancer cells. 23337876_1 overexpression of mir-199a-5p inhibits dram1 and beclin1 expression in mcf7 cells, while it enhances expression of these genes in mda-mb-231 cells. 26012781_1 in this study, we found that mir-218 could inhibit growth and metabolism in gliomas by directly targeting e2f2. 26012781_2 subsequently, we found that e2f2 was a direct target gene of mir-218, and the role of mir-218 as a tumor suppressor was realized by directly targeting e2f2. in addition, we preliminarily found that mir-218 may affect the metabolism of glioma cells by directly targeting e2f2. 26463716_1 previous studies revealed a mir-92 target sequence in the 3- utr of p57, a tumor suppressor; mir-92 binding to this site inhibits p57 expression in a variety of cancers . in fig. 26463716_3 these results suggest that mir-92a inhibits p57 translation, not transcription. 24677135_2 luciferase reporter assay results showed that mir-502-5p could bind to the 3'-untranslated region of the traf2 gene, thus, exerting an inhibitory effect on traf2. 19202062_2 this suppression of the luciferase activity was specific to mir-145 because the mutated mir-145 at the seed sequence lost its suppressive activity . 19202062_3 at the same time, real-time rt-pcr analysis of the same transfected cells indicated that c-myc mrna was also suppressed by >50% in the mir-145 transfected cells as compared with vector control . 19202062_4 together, these results suggest that c-myc is a targetfor mir-145. 24356001_1 the regulation of mir-375 on yap1 expression was determined by dual luciferase reporter assay, qrt-pcr and western blot. 24356001_2 the mouse yap1 was a target gene of mir-375, and mir-375 could target the 3' utr of yap1 mrna to decrease its protein and mrna levels. 24356001_3 these results indicate that mir-375 regulates the expression of yap1 by mrna cleavage. 23217387_1 a 24-hours incubation of ins-1 cells with palmitate significantly decreased cell viability, increased cell apoptosis and led to the activation of microrna-34a and the suppression of sirtuin 1. a co-incubation with glp-1 protected the cells against palmitate-induced toxicity in association with a reduction in palmitate-induced activation of microrna-34a. 23217387_2 furthermore, palmitate-induced apoptosis was significantly increased in cells that were infected with microrna-34a mimics and decreased in cells that were infected with microrna-34a inhibitors. 19782699_1 consistent with this hypothesis, we confirmed by 3'-utr dual-luciferase activity assay and by western blot that the member of this family more clearly down-regulated during sips in hdf and htm cells, mir-106a, also target the p21cdkn1a mrna . 19782699_2 as shown in figure 4d, while the down-regulation of p21cdkn1a mediated by mir-106a mimic was observed regardless of whether p53 was inhibited or not, the induction of p21cdkn1a expression mediated by mir-106a antagomir was prevented by inhibition of p53 by sirna. 26722410_1 figure 4 igf1r is a target of mir-98 in oscc cells. 26722410_2 figure 5 mir-98 suppresses oscc progression partially by targeting igf1r. in conclusion, the present study showed that mir-98 was significantly downregulated in oscc tissues and cell lines. 26722410_3 overexpression of mir-98 suppressed growth and metastasis of oscc cells by targeting igf1r. 22536440_2 it was found that mir-129-5p directly inhibited the expression of vcp in several hcc cell lines. 22536440_3 this suggested that both targetsites in the 3'-utr of vcp mrna were essential for the regulation of mir-129-5p. 22536440_4 all of these results revealed mir-129-5p may be associated with the progression of hcc by inhibiting the expression of vcp. in conclusion, our results identified that mir-129-5p can directly inhibit the expression of vcp. 25635127_1 suggesting mir-181a and mir-181b inhibit embryo implantation through lif. 25635127_2 taken together, these results demonstrate that mir-181 lowers the functional levels of uterine lif, and administration of lif improves embryo implantation in mice with increased expression of mir-181. 25635127_3 the results showed that mir-181a/b was able to decrease lif expression in both p53 knockdown and control cells , indicating that the regulation of lif expression by mir-181a/b is independent of p53. 25635127_4 these data indicate that mir-181 is able to downregulate lif expression, therefore inhibiting the embryo implantation process. 22249617_1 fig. 7 determination of hmga1 as a direct target of hsa-mir-124a in mb cells. 22249617_4 taken together with the current findings of hmga1 being one of hsa-mir-124a-檚 target and the hmga1-mediated control of mb cell growth and metastatic potential, the tumor suppressive roles of hsa-mir-124a in mb are mediated, at least partially, through modulation of hmga1 expression by targeting its 3' utr of hmga1 gene and thus cdc25a expression. 23665284_1 the ectopic expression of mir-20a could induce epithelial-mesenchymal transition and enhance metastasis of gbc cells in vitro and in vivo, by directly targeting the 3 ' utr of smad7, and subsequently promoting nuclear translocation of b-catenin. 23665284_2 smad7 , a potential inhibitor of tgf-b1 signaling pathway, was identified as the direct target of mir-20a. 23665284_3 our present data further demonstrate that smad7 is a direct target of mir-20a and that mir-20a-mediated inhibition of smad7 is dependent on a conversed motif in the 3' utr of smad7 . 21390040_1 a commentary on microrna-141 confers resistance to cisplatin-induced apoptosis by targeting yap1 in human esophageal squamous cell carcinoma. 22096245_1 we demonstrate that mir-155 directly down-regulates hgal expression by binding to its 3'-untranslated region, leading to decreased rhoa activation and increased spontaneous and chemoattractant-induced lymphoma cell motility. 22096245_2 overall, these findings suggest that mir-155 regulates hgal expression mainly at the protein translation level. 22096245_3 this observation suggests that mir-155 posttranscriptionally regulates hgal expression mainly by interacting with the m2 binding site in hgal 3'-utr. 26759383_1 mutl homolog 1 is the direct target of mir-148b which is required for the regulatory role of mir-148b in radioresistance. 26759383_2 taken together, these results demonstrate that mir-148b can directly regulate mlh1 expression level. 26759383_3 these results suggest that mlh1 is required for the regulatory role of mir-148b in radioresistance. 26263387_1 fig 4 tp53rk and bcl2l2 are direct targets of mir-630. 26263387_2 overall, these data demonstrated that mir-630 can directly bind to the 3'-utr of tp53rk and bcl2l2 to repress gene expression. 21738213_1 in microarray analysis, we found that among the candidate target genes the expression levels of trp53inp1 mrnas were reduced in 32dcl3 cells transduced with mir-125b . 21738213_2 the 3' utr of trp53inp1 contained one putative target site that matched the seed sequences of mir-125b. 21738213_3 trp53inp1 is a pro-apoptotic gene induced by cell stress,16-19 and its repression is involved in tumorigenesis.30,31 to confirm that trp53inp1 is a direct target gene of mir-125b, the wild-type 3' utr of trp53inp1 or the mutated 3' utr was cloned to downstream of the renilla luciferase open reading frame . 21738213_4 we performed luciferase assays and found that mir-125b directly represses the expression of the reporter gene with the trp53inp1-3' utr but not that with mutated 3' utr of trp53inp1 . 21738213_5 figure 3 mir-125b repressed expression of trp53inp1 and inhibited apoptosis of b cells. 21738213_6 collectively, these results indicated that mir-125b inhibits apoptosis of hematopoietic cells at least partly through repressing trp53inp1. 22593182_1 these results further verify that rbms1 is a real target of mir-383 and mediates, at least in part, the mir-383's effects on gc function. 22593182_2 these results indicate that mir-383 suppresses rbms1 expression through direct binding to its 3'-utr. 26780940_1 through bioinformatic analysis,we found that mir-27b harbored a putative binding site for fzd7 3'-utr . 26780940_2 the results showed that co-transfection of hek-293t cells with mir-27b mimics and luciferase reporter vectors containing the wt fzd7 3'-utr led to a significant decrease in luciferase activity, compared to nc mirna transfection . in contrast, the luciferase activity of luciferase reporter vectors containing the mt fzd7 3'-utr was not affected by mir-27b mimics transfection . 26780940_3 the data imply that mir-27b could target the 3'-utr of fzd7 directly. 26780940_5 pylori infection was significantly decreased by mir-27b overexpression in ags and bgc-823 cells. 26780940_6 taken together, these results demonstrated that mir-27b regulated fzd7 expression. 22128032_2 fig. 5. repression of nr3c1-3'-utr upon transfection with mir-101a, mir-142-3p, mir-433, and mir-96 vectors and combined transfection with mir-96+mir-101a and mir-96+mir-142-3p vectors, respectively 23856247_1 in this study, we report upregulation of the oncomir microrna -205 in multiple subtypes of nsclc, which directly represses pten and phlpp2 expression and activates both the akt/foxo3a and akt/mtor signaling pathways. 19424584_1 in the current study, an inverse relationship between the expression of mir-221/mir-222 and the cell cycle inhibitor p27kip1 was identified in u251 glioma cells. 19424584_2 co-suppression of mir-221/222 directly resulted in the up-regulation of p27kip1 in the tested cells, consequently, affects their growth potential by reducing a g1 to s shift in the cell cycle. 19424584_3 consistently, mir-221/222 knocked-down through antisense 2'-ome-oligonucleotides increased p27kip1 in u251 glioma subcutaneous mice and strongly reduced tumor growth in vivo through up regulation of p27kip1. 19424584_4 our results suggest that mir-221/222 is a regulator of the tumor suppressor gene p27kip1, and co-suppression of mir-221/222 expression in advanced gliomas may inhibit glioma cell proliferation by a mechanism involving the up-regulation of p27kip1 in vitro and in vivo. 26486082_3 exogenous mir-497 significantly down-regulated the mrna levels of anln and hspa4l , indicating that mir-497 can regulate the expression of these genes in npc cells. 26661155_1 taken together, these results experimentally verified cycs as a mir-34a target, which is associated with the reduction of mitochondrial oxidative phosphorylation in cecs. 22846564_1 mir-130a inhibits runx3 and activates wnt signaling. 22846564_2 upregulated mir-130a increases drug resistance by regulating runx3 and wnt signaling in cisplatin-treated hcc cell. 22846564_5 these results indicated that mir-130a inhibits runx3 and activates wnt signaling. 22846564_6 these results confirmed that upregulated mir-130a increases drug resistance by regulating runx3 and wnt signaling in cisplatin-treated hcc cell. 25414595_1 mir-133b regulates bladder cancer cell proliferation and apoptosis by targeting bcl-w and akt1. 20581456_1 knockdown of p53 in hct-116 cells severely reduces mir-34a induced apoptosis. 23826132_1 these results suggest that mir-338-3p suppresses the expression of ssx2ip at the post-transcriptional level, likely through binding to the 3'-utr of ssx2ip. 23826132_2 thus, we concluded that the cancer suppressor function of mir-338-3p in gc is at least partially through suppressing its target gene ssx2ip. 26054675_1 further investigations revealed that mir-498 directly targeted the 3 ' -utr of foxo3 to increase the expression of this gene, which in turn inhibited the proliferation of ovarian cancer. 26054675_2 in summary, our data indicate that mir-498 directly attenuated the expression of foxo3 by targeting of its mrna 3 ' utr in ovarian cancer cell lines. 26054675_3 therefore, our results demonstrate that mir-498 was able to inhibit the proliferation of ovarian cancer cells through direct targeting foxo3. 26054675_4 result of dual-luciferase assay showed that foxo3 was a direct of mir-498. 26211738_1 thereby it was ascertained that mir-7 had an inhibitory effect on myrip and pax6 through direct binding of their 3'-utr. 26211738_2 these results demonstrate that mir-7 could regulate the expression of myrip and pax6. 20080834_1 statistically significant repression of luciferase activity was observed in 293t cells co-transfected with the mir-181c precursor molecule and a reporter vector containing the notch4 or kras 3'-utr target site . 20080834_2 on the other hand, no notable alteration of luciferase activity was detected between the pre-mir-181c transfectant and the control counterpart in the case of notch2. 20080834_3 to determine whether the predicted target sites for mir-181c in the 3'-utrs of notch2/4 and kras mrnas were responsible for the translational repression, we performed dual luciferase reporter assays with vectors containing the 3'-utr target sites downstream of the luciferase reporter gene . 20080834_4 statistically significant repression of luciferase activity was observed in 293t cells cotransfected with pre-mir-181c and a reporter vector containing the notch4 or kras 3'-utr target site . 26062603_1 inbrief,estrogen down-regulated expression of mir-181a, a negative modulator of fasl targeting the 3'-utr of fasl mrna. 26062603_3 taken together, these results indicate that estrogen suppresses mir-181 at omaintain fasl protein accumulation. 17668390_1 we further experimentally investigated one of these target sites for hsa-mir-155, within the 3' utr of the human agtr1 gene that contains snp rs5186. 17668390_4 thus, the 1166c allele may be functionally associated with hypertension by abrogating regulation by hsa-mir-155, thereby elevating agtr1 levels. 17668390_5 since hsa-mir-155 is on chromosome 21, we hypothesize that the observed lower blood pressure in trisomy 21 is partially caused by the overexpression of hsa-mir-155 leading to allele-specific underexpression of agtr1. 26774446_1 target prediction analysis and dual luciferase reporter assays confirmed that low-density lipoprotein -receptor-related protein 5 was a direct target of mir-23a. 26774446_2 our results indicate that mir-23a, which is downregulated during osteogenic differentiation of hbmscs, inhibits the differentiation process by targeting lrp5. 26774446_3 taken together, these results indicate that mir-23a inhibits osteogenic differentiation of hbmscs by targeting lrp5 and subsequently depressing the wnt/-beta-catenin signaling pathway. 26774446_4 moreover, a dual luciferase reporter assay identified lrp5 as a direct target of mir-23a. 26436647_1 rasa1 and nfat5 are genuine mir-223 target genes and important for m2 macrophage activation. 26436647_2 taken together, these results demonstrate that rasa1 and nfat5 are bona fide mir-223 target genes and play critical roles in ppargamma/mir-223 regulatory axis-mediated m2 macrophage activation. 22115756_1 since mir-200c regulates e-cadherin , a marker of epithelial identity, by directly targeting its transcriptional repressor zeb1 , we also analyzed these genes as positive controls to monitor the efficiency of mir-200c loss-of-function in our experiments. 22115756_2 as expected, the direct target zeb1 was upregulated and cdh1 was downregulated after mir-200c loss-of-function . 25859932_1 otx2 has been reported to be a target of mir-206. 25859932_2 mir-206 overexpression in medulloblastoma cells downregulates otx2 and inhibits medulloblastoma cell growth. 25515700_2 bioinformatic analysis combined with experimental analysis revealed that mir-203 directly targeted e2f3 via the conserved mir-203 target site within the e2f3 3'-untranslational region. 26891231_1 prediction algorithms determined that n-myc is a target of mir-449a and identified the likely mir-449a:n-myc binding sites, confirmed by luciferase assays and targeted mutagenesis. 26891231_2 thus, n-myc plays an important role in embryonic lung development and the data presented herein point to a role for mir-449a as a regulator of n-myc, as confirmed by luciferase assays. 19435910_1 epigenetic down-regulation of mir-124a induced an up-regulation of its target cdk6, and phosphorylation of retinoblastoma and contributed to the abnormal proliferation of all cells both in vitro and in vivo. in line with the studies in cell lines, patients with methylation of hsa-mir-124a showed a significant up-regulation of cdk6 expression compared with nonmethylated patients . 19435910_2 thus, to determine the potential role of hsa-mir-124a in the regulation of all cell growth in all cells and to experimentally validate if cdk6 is a targetfor hsa-mir-124a in all, we analyzed cdk6 mrna and protein levels in human all-derived cell lines after reexpression of hsa-mir-124a. 22367714_1 mir-450b-5p inhibited pax6 expression and corneal epithelial fate in vitro, altogether, suggesting that by repressing pax6, mir-450b-5p triggers epidermal specification of the ectoderm, while its absence allows ocular epithelial development. 22367714_2 this data indicated that mir-450b-5p can specifically bind to the 3'-utr of pax6 and may inhibit pax6 expression. 22367714_3 as expected, pax6 expression was attenuated by the presence of pre-mir-450b-5p , confirming that pax6 is a target of mir-450b-5p, and indicating that the decrease in the levels of mir-450b-5p is contributing to the induction in pax6 protein expression during early neuroectodermal commitment of hescs . 21165896_1 we demonstrated that mir-126 directly inhibits dnmt1 translation via interaction with its 3'utr, and that overexpression of mir-126 in cd4 + t cells can significantly reduce dnmt1 protein levels. 21165896_2 overexpressing mir-126 in healthy donor cd4 + t cells caused 23408429_1 collectively, our results point to a protective function of mtdh against trail-induced death, whereby it inhibits the intrinsic apoptosis pathway through mir-16-mediated bcl-2 up-regulation and the extrinsic apoptosis pathway through caspase-8 down-regulation. 20351193_1 additionally, we identified two micrornas, let-7a and mir-125b, which targetthe kb-ras2 3' untranslated region . 20351193_2 lps induces let-7a and inhibits mir-125b expression in human macrophages, and pretreatment with estradiol abrogates these effects. 20351193_3 3'utr reporter assays demonstrate that let-7a destabilizes the kb-ras2 3'utr, whereas mir-125b enhances its stability, resulting in decreased kb-ras2 in response to lps. 20351193_5 these findings indicate a coordinated regulation of let-7a and mir-125b by estradiol and lps for the net effect of increasing kappab-ras2 expression in the presence of estradiol. 20034472_1 the result was that overexpression of mir-126 in a549 cells could increase egfl7 expression. 20034472_2 furthermore, the most notable finding by cell proliferation related assays is that mir-126 can inhibit a549 cells proliferation in vitro and inhibit tumor growth in vivo by targeting egfl7. 20034472_3 as a result, our study demonstrates that mir-126 can inhibit proliferation of non-small cell lung cancer cells through one of its target, egfl7. 20065103_1 together, these results demonstrate that med1 is a functional cellular targetfor mir-205. 20065103_2 notably, whereas the activity of the med1 3'-utr reporter was predictably attenuated by hypoxia, this effect was abolished in the med1 reporter that harbored a mutant site 3 mir-205 binding element , supporting the role of mir-205 in hypoxia-mediated down-regulation of med1 expression. 26879754_2 overall, this study revealed that mir-183 promotes glioma cell proliferation by targeting nefl, and also demonstrated that mir-183 could be a potential target for gbm treatment. 26879754_3 and further revealed that up-regulation of mir-183 could promote cell proliferation and growth by regulating the targets of nefl via mtor signaling pathway. 26879754_4 these results indicate that nefl is a novel target of mir-183, and the abnormal expression of mir-183 leads to mtor pathway change via targeting of nefl. 26617722_1 overexpression of mir-101 decreased expression of its target gene cox-2 and inhibited proliferation and invasion, and promoted apoptosis to suppress tumorigenicity. 26617722_2 mir-101 suppressed cell growth, inhibited cell migration, enhance cell apoptosis, and mir-101 negative regulating its target gene cox-2 in cervical can- cer cell lines. 26617722_3 our findings suggest that mir-101 and its target gene cox-2 may play important roles in the pathogenesis of cervical cancer, and mir-101 may be potential diagnostic or therapeutic targets for cervical cancer. 25535087_1 targeted inhibition of urat1 expression by mir-34a. 25535087_2 by assessing the expression level of the reporter gene, mir-34a was found to significantly inhibit the expression of luciferase in the psi-urat1-mir34a-bs construct, strongly implying that mir-34a could inhibit the expression level of urat1. 26482612_1 in this report, we demonstrated that mir-221 reduced the sensitivity of cervical cancer cells to gefitinib by targeting the phosphatase and tensin homolog deleted on chromosome ten /phosphatidylinositol-3 kinase /akt pathway. 26482612_2 these data suggest that pten is a direct target of mir-221 in cervical cancer . 26482612_3 the luciferase reporter assay in cultured cervical cancer cells also showed that pten was a target gene of mir-221. 21592405_1 we found that mir-335 targeted a potential tumor suppressor daam1 in astrocytoma cells, which promoted several malignant features such as growth and invasion, whereas mir-335 inhibition could potently induce growth arrest, apoptosis and invasion repression both in vitro and in vivo. 21592405_2 interestingly, after introducing mir-335 into c6 cells and normal astrocytes, a dramatic downregulation of daam1 protein in a dose-dependent manner was concurrent with an unaltered daam1 mrna , indicating a posttranscriptional modulation of mir-335 on daam1. 21592405_3 these data indicate that mir-335 may inhibit the expression of daam1 at posttranscriptional level by directly targeting the 3'-utr of daam1 mrna. 21592405_4 taken together, all these data suggest that daam1 is potentially involved in mir-335-regulated growth and invasion. 26587789_2 these data indicate that mir-98 inhibits il-6/stat3 signaling pathway in idd. 19333007_1 experments showed that, in the foreign hfq condition, while all tested omp mrnas were successfully cleared, even though hfq strongly binds the major porin mrnas, it fails to initiate the downstream regulatory process, i.e., the srna-mediated decay, since the regulatory srnas mica and rybb are detectable in high levels. 21712475_1 this indicates highly effective inhibition by mir-7 against the full length of egfr 3'-utr. 21712475_2 because mir-7 was proven to effectively suppress the expression of mrna of total egfr, it can also suppress its downstream signals such as akt . 21712475_3 western blot analyses showed a direct inhibitory effect against total egfr by mir-7, as well as the suppression of akt phosphorylation . 21712475_5 the inhibitory effects of total irs-1 and raf-1 by mir-7 were shown to varying degrees in the 4 cell lines . 19890883_1 in vitro studies using the cell lines mpnst-14 and mpnst-724 show that exogenous expression of p53 or mir-34a promotes apoptotic cell death. 19890883_2 in addition, exogenous expression of p53 in mpnst cells induces mir-34a and other mirnas. 21795477_1 mir-218 target rictor inducing the activation of a tor-akt signaling pathway. in western blotting of rictor and junb, their protein levels were markedly reduced in mir-218- and mir-585-transfectants, respectively, compared with their control counterparts . 21795477_2 these findings, together with the results of western blotting, suggest rictor and junb to be a novel direct target of mir-218 and an indirect target of mir-585, respectively. 21795477_3 therefore, we focused on rictor as the most likely target of mir-218, and conducted further analyses to explore the underlying molecular mechanisms of oral carcinogenesis. 24577088_1 the mir-210 overexpression and iscu1/2 downregulation was observed in a dose- and time-dependent manner. 24577088_2 these results verified that mir-210 regulates the expression of iscu1/2 by binding to the predicted target site in the 3 ' -utr of iscu1/2 24854843_4 erbb3, il-6r and cdk6 may be the targeted genes of mir-3928. 24036151_2 luciferase reporter assays indicated that mir106b and mir93 targeted atg16l1 messenger rna. 24036151_3 mir106b and mir93 reduced levels of atg16l1 and autophagy; t 23297411_1 subsequent in silico analysis revealed that the 3- utr of the mouse hsp70 gene contained a mir1 complementary sequence . 23297411_2 subsequent western blot analysis revealed that dex-mediated reduction of hsp70 levels was blocked in c2c12 myotubes transfected with antagomir1 , thus confirming a direct role for mir1 in loss of hsp70 during dex-induced muscle atrophy. 23297411_3 these data confirm that mir1 targets hsp70 in differentiated myoblasts. 26191199_1 to determine whether trim29 is a direct target of mir-185, we cloned a part of the 3'-utr region of trim29 containing the potential mirna binding site into a dual-luciferase reporter. 26191199_3 trim29 was regulated negatively by mir-185 mimics at both the transcriptional and protein levels . 24412052_1 ectopic mir-378a-3p or mir-378a-5p expression inhibited cellular proliferation and colony formation, induced apoptosis and g1-phase cell cycle arrest in crc cells, but had no effect on migration and invasion of crc cells. 21406115_1 casp9, as one of the candidate target of mir-133a, was compared during ir after the mir-133a mimic or amo-133a was transferred into the myocardium. 21406115_2 to see whether mir-133a regulated the casp9 protein during ir, mir-133a mimic or amo-133a was transferred into the myocardium before ir. it was found that the expression of casp9 protein was uperegulated by amo-133a and down-regulated by mir-133a mimic . 21406115_3 the results of flow cytometry and tunel assay showed that up-regulation of mir-1 and mir-133a decreased apoptosis of cardiomyocytes. 21406115_4 mir-133a mimic down-regulated casp9 protein expression and attenuated ir-induced apoptosis. 25425543_1 microrna-141 inhibits cell proliferation and invasion and promotes apoptosis by targeting hepatocyte nuclear factor-3-beta in hepatocellular carcinoma cells. 20080637_1 specifically, we show that mir-18a and mir-19a target and repress the expression of estrogen receptor-alpha , a ligand-inducible transcription factor implicated in neuronal differentiation. 20080637_2 to demonstrate that mir-18a and mir-19a directly regulate esr1 expression, we transfected a esr1 3'-utr luciferase reporter construct together with mir-18a precursors into hek-293 cells and noticed an ~60% reduction in luciferase activity compared to cells transfected with the scramble control . 20080637_3 taken together, these data suggest that esr1 expression may be negatively regulated via both mir-18a and mir-19a 3'-utr mirna binding sites. 25783528_1 fig. 4 frk was the target of mir-1290. 25783528_2 the cells with wild 3'-utr of frk vector showed significantly decreased luciferase activity with mir-1290 mimic compared with the mir-control group . 25783528_3 all these data indicated that antagomir-1290 inhibited the proliferation, clonogenicity, invasion, and migration of cd133+ cells by targeting frk. 23426184_1 these data suggest that hif1alpha-induced let-7 and mir-103/107 suppressed ago1 expression under hypoxia. 23426184_2 let-7 and mir-103/107 target ago1. 23426184_3 our current study suggests that hrms such as let-7 and mir-103 targeting ago1 results in translational desuppression under hypoxia. 22469983_1 further in vitro observations showed that enforced expression of mir-424 inhibited cell growth by both enhancing apoptosis and blocking g1/s transition, and suppressed cell migration and invasion in two human cervical cancer cell lines, siha and caski, implying that mir-424 functions as a tumor suppressor in the progression of cervical cancer. 22469983_2 interestingly, overexpression of mir-424 inhibited the expression of protein checkpoint kinase 1 and phosphorylated chk1 at residues ser345 and decreased the activity of luciferase-reporter containing the 3'-untranslated region of chk1 with predicted mir-424-binding site. 22039399_1 computational target prediction analysis indicated that cxcr4 is one of the consensus putative targets of mir-150 relevant to stem cell mobilization . 22039399_2 to verify microarray profiling results, we performed real time pcr and confirmed that mir-150 expression was markedly reduced in bm-derived mncs from ami mice . 22039399_3 as shown in figure 3c, knockdown of mir-150 by anti-mir-150 markedly reduced cxcr4 protein expression in mncs, indicating cxcr4 is a putative target of mir-150 in mncs. in addition, knockdown of mir-150 in mncs by lentiviral vector significantly increased cxcr4 expression . 22039399_4 interestingly, we found that in vivo transplantation of mncs lacking mir-150 expression into the irradiated wild type mice resulted in increased number of mncs in pb released from bm as compared to that of mncs transducing scramble , indicating that mir-150 plays a critical role in mnc mobilization in bm through cxcr4 regulation . in conclusion, our results demonstrated that mir-150 downregulation by ami enhanced cxcr4 expression, leading to enhanced bm-mncs mobilization and migration. 25524579_2 moreover, we also found mir-181 reduction was associated with increased bcl-2 levels and mir-181 was further suggested to exert its pro-apoptotic function mainly through targeting bcl-2 expression. 25625784_1 c-jun is directly regulated by mir-29c. 25625784_2 figure 3. c-jun is a direct target of mir-29c as determined by luciferase reporter assay. 25625784_3 western blot results revealed a significantly decreased expression of c-jun in the cells transfected with the mir-29c mimic; however, the expression of c-jun was increased in the cells transfected with the mir-29c inhibitor . 26186555_1 functional assays indicated that the mthfr 2244 a → g substitution could increase the binding activity of hsa-mir-1266 with the mthfr 3' utr. the mthfr 2264 a → g substitution could decrease the binding activity of hsa-mir-616 with the mthfr 3' utr. 26186555_2 therefore, hsa-mir-1266 and hsa-mir-616 may affect mthfr mrna expression by degrading mrna. 19029026_1 the target of mir-34a was predicted by bioinformatics and confirmed using a luciferase assay. in addition, expression of c-met and cell cycle-related proteins was determined by western blotting and immunofiuorescence after the introduction of mir-34a. 19029026_3 mutations of the two c-met 3'-utr-binding sites completely abolished the ability of mir-34a to regulate luciferase expression . 19029026_4 these results demonstrated that c-met is a potential target of mir-34a. 19029026_5 to further confirm the downregulation of c-met by mir-34a, c-met expression was also examined by immunostaining. 23635652_1 ectopic expression of mir-142-3p inhibited cell proliferation, measured by electric cell-substrate impedance sensing, and decreased hsp70 expression, measured by real-time pcr and immunoblotting, compared with controls. 23635652_2 we showed that mir-142-3p directly binds to the 3'utr of hsp70, and that this interaction is important as hsp70 overexpression rescued mir-142-3p-induced cell death. 23635652_3 we found that mir-142-3p regulates hsp70 independently of heat shock factor 1. overexpression of the mir-142-3p mimic inhibited at least 31% of hspa1b mrna expression following 24 h of transfection . 23635652_4 similarly, overexpression of mir-142-3p inhibited total hsp70 protein expression by at least 50% following transfection for 72 h . 23635652_5 these results show that ectopic expression of mir-142-3p decreases hspa1b mrna and protein levels. 22957142_1 together, these results indicate that the 3'utr of 5-lox but not cox-2 is a direct target for mir-219-2. 22957142_2 together, these results indicate that mir-219-2 selectively regulates 5-lox. 22957142_3 notably, the mir-219-2 but not mir-219-19s binding with the 3' utr of 5-lox provides direct evidence for decreased mir-219-2 expression in the delayed resolution challenges . 22995515_1 we used bioinformatics and quantitative polymerase chain reaction analysis to demonstrat that high-phosphate upregulated adamts-7 mrna and protein via mir-29a/b repression, which directly targeted the 3' untranslated region of adamts-7 in vsmcs. 22995515_2 our data reveal a novel mechanism by which adamts-7 upregulation by mir-29a/b repression mediates vascular calcifiation, which may shed light on preventing cardiovascular morbidity and mortality. 22995515_3 adamts-7 is a target of mir-29a/b in vsmcs. 22995515_4 therefore, mir-29a/b can negatively regulate adamts-7 mrna by targeting its 3'-utr. 22995515_5 the repression of mir-29a/b by risk factors such as high phosphate led to enhanced adamts-7 expression or comp degradation, upregulated bmp-2 osteogenic signaling in vsmcs and, ultimately, acceleratd vascular calcification. 26775556_1 thus, we concluded that mir-30c may have renoprotective effects by directly down-regulating ctgf expression in dn. 22565856_1 programmed cell death 4 , related to cell proliferation and apoptosis, was validated as a direct target of mir-21 by dual-luciferase reporter assay and gain and loss of function of mir-21 in afs and mfs. 22565856_2 pdcd4 knockdown with sirna partly rescued the reduced proliferation with mir-21 inhibition and alleviated the increased apoptosis induced by mir-21 inhibition in afs and mfs. 19688090_1 using mirna-targetprediction analyses and the array data, we listed up a set of likely target of mir-107 and mir-185 for g1 cell cycle arrest and validate a subset of them using real-time rt-pcr and immunoblotting for cdk6. 19688090_2 we note that both mir-107 and mir-185 transfection caused down-regulation of cyclin e1 and cyclin dependent kinase 6 mrna levels although the suppression level of cdk6 by mir-185 is modest . 19688090_3 we then confirmed by western blotting that cdk6 protein levels are also down-regulated by mir-107. 26157321_1 thus, mir-218 may inhibit the proliferation and invasion of pancreatic cancer cell line panc-1 and promote its apoptosis by suppressing the expression of its target gene hmgb1. 26157321_2 in conclusion, the mir-218 expression decreases in human pct and cell lines. 26157321_3 mir-218 can negatively regulate the hmgb1 protein expression and inhibit the proliferation and invasion of pancreatic cancer cells. 16096373_1 mir-17 cluster prevents excessive e2f1 activity, and thereby apoptosis, in response to activation of c-myc. 19148268_1 our data indicate that mir-198 functions to restrict hiv-1 replication in monocytes, and its mechanism of action appears to involve repression of cyclin t1 expression. 23142282_2 after co-transfection with mir-29c mimics, the luciferase activity of the wild-type 3'utr reporter gene reduced significantly, whereas the activity of the mutant reporter gene was not affected , confirming that mir-29c can bind to the tiam1 3' utr. 23142282_3 taken together, these findings suggest that mir-29c can negatively regulate the expression of tiam1 in npc by directly targeting the tiam1 3' utr. 26796749_1 luciferase reporter assay, qpcr and western blot analysis confirmed that mir-10b-5p and mir-363-3p bind directlyto the 3'-utr of creb1 mrna and inhibit mrna and protein expression of creb1. 26796749_2 furthermore, using computational prediction followed by experimental confirmation, mir- 10b- 5p and mir- 363- 3p were found to bind directly to the 3'-utr of creb1 and downregulate creb1. 26796749_4 4d, when transfected with the mir-363-3p mimics, identical results were also obtained in the 293t , hela , 786-慜 and achn cells , suggesting that mir-10b-5p and mir-363-3p may suppress the expression of creb1 by targeting the putative binding site in the 3'-utr. 26796749_5 luciferase reporter assays confirmed that mir-10b-5p and mir-363-3p target creb1 directly. 26175848_1 the data suggested that mir-29c expression can be stimulated by igf-1 treatment. 26175848_2 these results supported the bioinformatics prediction that the 3'-utr of igf-1 mrna could be a target of mir-29c . 26175848_4 we examined the mrna expression levels of pi3k and akt, which were key components that related to huvec angiogenesis . in the rt-pcr results, a 3.3-fold induction of pi3k mrna and a 2.4-fold induction of akt were observed in mir-29c mimics. 26175848_5 the igf-1 and vegf inductions were significantly reversed by mir-29c mimics and controls . 26175848_6 the data showed that overexpression mir-29c can down-regulate igf-1, pi3k/akt and vegf mrna expression. 25957028_2 in this study, we found that in cultured astrocytes, tnf-alpha, il-1-beta, or lipopolysaccharide induced rapid traf6 upregulation and delayed mir-146a-5p upregulation. 25957028_3 taken together, the results suggest that mir-146a-5p attenuates neuropathic pain partly through inhibition of traf6 and its downstream jnk/ccl2 signaling, mir-146a-5p is increased by the activation of traf6/jnk pathway. 26044563_1 targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay, showing that mir-449b binds to the 3'-utr of met mrna, to inhibit its expression in tc cells. 26044563_2 these data suggest that mir-449b targets met to suppress its expression. 26044563_3 specifically, we found that the 3'-utr of met mrna was targeted by mir-449b at two binding sites, suggesting a strong effect on the translational regulation of met mrna by mir-449b. 26044563_4 interestingly, mir-449a is similarly binding to met mrna. 22119805_1 furthermore, the luciferase reporter assayconfirmed caspase-3 to be a target of mir-378, and the apoptosis and cell injury caused by mir-378 inhibitor in both normoxic and hypoxic cells were abolished by a caspase-3 inhibitor. 22119805_3 one mir-378-binding site was identified within the 3'-utr of caspase-3 mrna . 22119805_4 compared with the negative control rna, the mir-378 mimic significantly suppressed the activity of the luciferase reporter fused with caspase-3 3'-utr by 26% , suggesting the inhibition of mir-378 on caspase-3 expression through its 3'-utr. 22119805_5 these results indicate that mir-378 inhibits the synthesis of caspase-3 proteins, likely through post-transcriptional mechanisms. 18166281_1 since apeg3 is localized in the 3'utr of peg3 and the apeg3 transcript can base-pair with the peg3 transcript, it is more likely that apeg3 is involved in post-transcriptional regulation of the peg3 transcript. 18166281_8 the detection of human apeg3 in thalamus is somewhat consistent with the expression of rat apeg3 in a very specialized cell type, magnocellular neurons of hypothalamus . in sum, this series of experiments confirm the expression of apeg3 in the brain tissues of mouse, cowand human, and also the paternal allele-specific expression in mouse brain. 26350953_1 bioinformatic analysis and luciferase reporter assay demonstrated that mir-204 directly targeted and regulated the expression of bcl-2. 26350953_2 these results demonstrated that bcl-2 is targeted and regulated by mir-204. 26350953_3 bioinformatic analysis and luciferase reporter assay demonstrated that the expression of bcl-2 was directly regulated by mir-204 under normal oxygen and hypoxic conditions. 21647251_1 timp3 and tiam1, direct target of mir-21, were verified to be regulated by mir-21 in vitro and in vivo, indicating that these two molecules might contribute to mir-21-induced keratinocyte migration. 21647251_2 the above data implied that timp3 and tiam1 might be responsible for mir-21-promoted keratinocyte migration. 21647251_3 in addition, we found expression levels of timp3 and tiam1 were decreased at control wound edge, but not at wound edge treated with mir-21 as , indicating that mir-21 promoted keratinocyte migration possibly via inhibiting the expression of timp3 and tiam1 in re-epithelialization process. 26064240_3 additional experiments demonstrated that restoration of mir-592 significantly decreased the proliferation of sw48 cell lines, whereas mir-592-in had the opposite effect, probably through post-translationally down-regulating ccnd3 expression by targeting its mrna 3'-utr. 22378639_3 this indicates that the endogenous ana transcript is affected in a manner consistent with regulation by mir-124. 22378639_4 this suggests that mir-124 can act directly via this target site to repress ana expression. 22378639_5 taken together, these experiments provide evidence that mir-124 can act directly via the site identified in the 3' utr to regulate ana mrna levels in vivo. 26893712_3 4b, mir-155 depletion suppressed the transcription activities of nf- 魏 b and ap-1 in a549/dox cells. 26893712_4 the present results demonstrated the ability of mir-155 to positively regulate the activity of nf- 魏 b and ap-1. 21778999_1 third, we demonstrated that mir-16 directly interacts with vegf mrna at the 3'-untranslated region and that the regulation of vegf by mir-16 occurs at the translational level. 21778999_2 altogether, these results suggest that mir-16 downregulation contributes to a decrease in vegf levels in alk + cells. 21778999_3 we conclude that, in alk + cells, vegf mrna is a targetfor mir-16 binding and that vegf expression is controlled, at least in part, by the amount of mir-16. 21778999_4 together, these results suggest that the alk oncogene is able to induce vegf expression, probably through both transcriptional and translational regulation, and involving both transcription factor hif1-a and mir-16. 21778999_5 collectively, these results suggest that a decrease in mir-16 may be associated with an increase in vegf protein levels in a substantial proportion of human alk + alcl. 24335901_2 luciferase reporter assay showed a direct binding of mir-675 to 3'-untranslated region of mitf. 26497554_1 taken together, we conclude that ing5 is a target gene of mir-331-3p and ing5 expression is inhibited by mir-331-3p in hcc cell lines. 25086243_2 additionally, mir-190 down-regulates nr4a3, a cellular immediate-early gene for ebv reactivation, and inhibits the expression of the viral immediate-early gene bzlf1 and viral lytic dna replication. 26209100_1 meanwhile, we found that cytoplasmic polyadenylation element binding protein 4 might be involved and serve as a direct target of mir-1246 in nsclc. 26209100_2 cpeb4 knockdown substantially enhanced nsclc migration and invasion resembling the effect of mir-1246 in nsclc. 26209100_3 this result suggests that mir-1246 binds to the 3- utr of cpeb4 via the predicted binding site. 26209100_4 collectively, these results indicated that mir-1246 could negatively modulate cpeb4 expression by directly targeting its 3- utr. 26209100_5 these results suggested that cpeb4 might be a direct target of mir-1246 in nsclc. 26893763_3 these results suggest that eef2k mrna was a direct target of mirna-877. 26202355_1 based on the results of an in-silicon analysis, cox-2 was identified as a virtual target gene of mir-146a . 26202355_2 we showed that the upregulation of mir-146a caused by transfection of the mimics substantially suppressed both mrna/protein expression of cox-2 and production of pgi2 in the human pasmcs 24573672_1 impaired mitophagy in response to hypoxia caused by mir-137 is reversed by re-expression of fundc1 and nix expression vectors lacking the mir-137 recognition sites at their 3' utr. 21402790_1 moreover, bioinformatics analyses revealed a highly conserved putative mir-708 binding site in the 3- untranslated region of rhodopsin, which, like mir-708 itself, is highly conserved among mammals . 21402790_2 together, our results suggest that mir-708 targets rhodopsin mrna, resulting in its decreased expression in mammalian cells. 21402790_3 here, we show that the intronic mirna mir-708 is regulated by er stress and provide evidence that one of its roles is to control expression of rhodopsin. 26617789_1 our analysis revealed that axin2 was a potential target of mir-374a based on putative target sequences at position 1321-1327 of the axin2 3'-utr. 26617789_2 luciferase reporter assay showed that mir-374a significantly decreased the luciferase activity of the axin2 3'-utr but not that of the mutant in mg63 cells. 26617789_3 taken together, these data strongly suggest that axin2 is a direct target of mir-374a in os. 19714650_1 the induction of cell apoptosis after intraarticular injection of double-stranded mir-15a occurs through inhibition of the translation of bcl-2 protein in arthritic synovium. 21352815_1 we also found that microrna-650 target a homologous dna region in the promoter region of the ndrg2 gene and represses its expression at the transcriptional level. 21352815_2 fig. 4. inverse relationship between expression of ndrg2 and mir-650. 21352815_3 to validate whether mir-650 directly recognizes the 3'-utrs of ndrg2 mrna or not, we cloned a sequence with the predicted targetsites of mir-650 or a mutated sequence with the predicted targetsites to downstream of the pmir luciferase reporter gene. 21352815_4 these data suggest that mir-650 may play a major role in the regulation of ndrg2. 25658748_1 further experiments using in silico prediction, luciferase reporter assay and western blot assay demonstrated that mir-185 directly targeted socs3 by binding to its 3'-utr. 25658748_2 the results showed that socs3 was a theoretical target gene of mir-185 in different species, including human, mouse and rat . 25658748_3 further we subcloned the wild type socs3 3'-utr fragment containing the mir-185 binding site or a corresponding mutant fragment into the pgl3-basic luciferase reporter vector respectively. 26254736_1 these results suggest that bcl2l1 is a direct target gene of rno-mir-665 in primary astrocytes. 26254736_2 rno-mir-665 was shown to regulate the expression of the anti-apoptotic gene bcl2l1 and inhibit excessive apoptosis of hippocampal astrocytes in vitro. 26762731_2 to further demonstrate the biological relevance of mir-143 targeting igfbp5, we analysed igfbp5 expression in facs-sorted satellite cells from the adult and old mice . 26762731_3 as anticipated, igfbp5 protein expression was inversely correlated with the expression of mir-143 in the satellite cells from both adult and old mice. 26912082_1 these results suggest that mir-30a exerts both direct and indirect regulation on the expression of p53. 26912082_2 taken together, these results suggest that mir-30a forms a feedback loop with cage and p53 to regulate the response to anti-cancer drugs. 26796268_2 timp3 depletion reversed the effect of a mir-221 inhibitor mimics on cell survival rates and apoptosis. 26796268_3 together, these results reveal that silencing of mir-221 enhances the sensitivity of human oral squamous cell carcinoma cells to adriamycin through upregulation of timp3 expression. 26796268_4 indeed, timp3 levels increased when mir-221 function was inhibited in both um2 and tca8113 cells . 20680360_1 using luciferase reporter assays, we showed that mdv1-mir-m4-5p and mir-155 efficiently targeted a common set of 3' untranslated regions of six cellular genes . in addition, we also investigated the interactions between mdv1-mir-m4-5p and mdv1-mir-m43p and viral mrnas encoding ul28 and ul32 in both reporter and western blot assays. 20680360_3 these data demonstrate that the mires detected in the 3' utrs of six cellular genes are functional targets of mdv1-mir-m4 and gga-mir-155 in 3' utr reporter assays. 26861791_1 these data suggested that mir-210 binded directly to the 3'utr of hif-3 alpha mrna. in the present study, mir-210 overexpression suppressed the mrna and protein expression levels of hif-3 alpha in the oa chondrocytes, confirming that hif- 3 alpha is a target for mir-210 in oa chondrocytes. 26861791_2 in conclusion, the present study demonstrated that mir-210 targeted hif-3 alpha , and thereby enhanced the proliferation of chondrocytes, stimulated the expression of col2a1 and reduced the expression levels of col10a1 and mmp13. 22701724_1 deregulated mirnas in hereditary breast cancer revealed a role for mir-30c in regulating kras oncogene. 22701724_2 luciferase assays confirmed that mir-30c bindhe 3'utr of kras transcripts and expression of pre-mir-30c down-regulated kras mrna and protein. 22701724_3 next, we checked whether mir-30c could affect kras mrna stability by performing qrt-pcr analysis in mda-mb-436 cells transiently transfected with either pre-mir-30c or scramble control. 22701724_4 indeed, we observed a sharp decrease in kras mrna levels upon transfections with pre-mir-30c . 22701724_5 therefore, modulation of kras protein level by mir-30c may explain at least in part, why down-regulation of mir-30c can promote proliferation and contribute to tumorigenesis. 23182878_1 ohsc can directly repress expression of shob. 26512718_1 mir-3619-5p targets 3'-utr of -beta-catenin mrna to inhibit its expression in nsclc cells 26396677_1 these data support the prediction that wave2 is a direct target of mir-146a in raw264.7 cells. 26700671_1 further study characterized the 3- untranslated region of cyclin d1 gene as a direct target of mir-520b in u87 and u251 cells as determined by luciferase reporter assays. 26700671_2 taken together, these results indicated that mir-520b directly targets cyclin d1 via its 3'-utr in gbm cells. 26700671_3 here, we revealed that cyclin d1 was a direct downstream target of mir-520b and acts to enhance cell growth potential in gbm cells. 26657345_3 the luciferase assay in our study also showed that mir-140-5p altered the luciferase activity of the 3'-utr reporters of wnt11 and tgfbr1, suggesting they are the direct targets. 26657345_4 these data identified tgfbr1 as a direct target of mir-140-5p. 25962782_1 moreover, significantly lower luciferase activity was detected in the cells transfected by the wild-type il-7 construct relative to the constructs containing the mutated mir-181c seed region , indicating that the il-7 transcript is a direct target of mir-181c. 26110567_1 these results suggested that mir-23a-3p can be suppressed by osthole in du145 cells and directly represses e-cad expression through binding to the 3'-utr of the human e-cad gene. 25417703_1 these results collectively substantiate that mir-146a represses egfr in mammary cells. 25417703_2 mutagenesis of the mir-146a binding sites within the egfr 3'utr resulted in increase in luciferase activity and also completely abolished the ability of mir-146a to regulate egfr 3'utr luciferase expression. 25417703_4 thus, we have demonstrated for the first time that egfr is a direct target of mir-146a. 23396279_1 we examined the effects of mir-375 on the expression of fzd8 during aec trans-differentiation. 23396279_2 the protein level of fzd8 was decreased significantly by mir-375 as shown in figure 8b. the mrna level of fzd8 was also decreased by 60% after mir-375 overexpression compared with cells infected with the control virus . 23396279_3 all together, mir-375 inhibits the expression of fzd8 at both protein and mrna levels. 26315342_1 these results indicated that mir-25 directly regulates mitf expression by binding to the predicted target sites in the 3'-utr of its mrnas. 20510161_1 mir-331-3p target 3 ' -utr of e2f1 gene. 20510161_2 to verify a direct interaction between mir-331-3p and the 3'-utr of e2f1, we cloned the 3'-utr region that is predicted to interact with mir-331-3p into a luciferase reporter vector. 19833767_1 mir-449a/b target and inhibits oncogenic cdk6 and cdc25a. 19833767_2 e2f1 directly transactivates mir-449 in parallel with its host gene, cdc20b. 19833767_3 mir-449a/b directly targetand inhibit cdk6 and cdc25a protein expression. 19833767_4 these loss-of-function data, together with overexpression data, demonstrate the inhibitory effects of mir-449 on cdk6 and cdc25a expression. 19833767_5 these results provide strong evidence that mir-449 target and down-regulates cdk6 and cdc25a through directly binding to their 3'-utrs. 22315408_2 finally, we show that mir-132 regulates schizophrenia- and development-associated genes including dnmt3a, gata2, and dpysl3. 22315408_3 finally, we demonstrated that several genes associated with neurodevelopment in mice and schizophrenia in humans, including dnmt3a, gata2, and dpysl3, are regulated by mir-132. 26309161_1 in addition, mir-183/182 and mir-96 directly inhibited the expression of sco2 and pdha1 through targeting their mrna coding sequences , respectively. 26309161_2 moreover, mir-183 increased the levels of hif1alpha protein through directly targeting cds of vhl mrna, forming a feedback loop of hif1alpha/mir-183/pvhl/hif1alpha. 26309161_3 as expected, western blot analysis showed that the exogenous expression of sco2 and pdha1 could be decreased by mirnas in the cells , suggesting that mir-183/mir-182 are able to target mrna cds of sco2 and mir-96 is able to target mrna cds of pdha1. 26309161_4 therefore, we conclude that mir-183/96/182 cluster is able to downregulate the expression of sco2 and pdha1 at the post-transcriptional level in breast cancer cells. 26309161_5 thus, we conclude that mir-183 enhances the stability of hif1alpha through targeting vhl mrna cds in breast cancer cells. 17540598_1 hence, mir-34a is a direct proapoptotic transcriptional target of p53 that can mediate some of p53's biological effects. 26779781_1 finally, the psmb8 mrna levels and mir-451 levels in 9 rcc samples were assayed by qrt-pcr, and data showed that there is a negative correlation between psmb8 mrna levels and mir-451 levels . 26779781_2 psmb8 was one of the targeted genes of mir-451. 26779781_3 the targeted gene of mir-451 is psmb8. 20423907_4 to validate the observation that hulc can reduce mir-372 expression in hcc, expression of mir-372 in clinical specimens was assessed by real-time pcr. 23554459_3 collectively, these results suggested that mir-638 selectively binds the 3'-utr of human nor1 mrna and inhibits its expression in human vsmcs.taken 23554459_4 together, these results demonstrated that mir-638 inhibits vsmc proliferation and migration, at least in part, via directly targeting the orphan nuclear receptor nor1. in this study, we demonstrated that mir-638 directly binds the 3'-utr of human nor1 mrna and down-regulates its expression. 23554459_5 furthermore, overexpression of mir-638 in human vsmcs markedly inhibited both basal and pdgf-bb-induced nor1 expression; therefore, implicating mir-638 as a novel post-transcriptional regulator involved in the regulation of nor1 in vsmcs. 21439283_2 mir-126 overexpression in h69 cells caused more than a 50% reduction in slc7a5 mrna levels, and also a slight suppression of plk2 mrna expression, as determined by qrt-pcr . 21439283_3 subsequent western blot analysis of slc7a5 and plk2 demonstrated that while mir-126 overexpression resulted in decreased slc7a5 protein levels, plk2 protein levels did not change significantly . 21439283_4 slc7a5 expression was also suppressed in pre-mir-126 transfected htb-172 cells . 21439283_5 fig. 4. slc7a5 is a direct target of mir-126. 20460378_1 microrna-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic bcl-2 antagonist killer 1 expression. 21170085_1 furthermore, we show the interaction of mir-410 or mir-650 with cdk1-3'utr by luciferase assays. 21170085_2 the better results, in these gain- and loss-of-function studies, obtained with the association of both mir-410 and mir-650 argue for their cooperation in the regulation of cdk1 expression. 21170085_3 figure 4 cdk1 is a target of mir-410 and mir-650. 21170085_4 rt qpcr analysis of mir-410, mir-650 and mir-16 expression in mcf7-p16 and controls . 21086164_1 the reciprocal correlation of expression between mir-373 and mbd2 encourage us to explore whether mir-373 is a negative regulator of mbd2. 21086164_2 take together, these observations suggest that the predicted complementary sequence in mbd2-3' utr is a functional element of mir-373. in conclusion, in this study we demonstrate that mir-373 is one negative regulator of mbd2. in hilar cholangiocarcinoma, down-expression of mir-373 led to an increase of mbd2, which in turn suppresses methylation mediated genes such as rassf1a. 19574298_1 the data further suggested that let-7 binding to c-myc mrna is required for hur-mediated inhibition of c-myc expression. 19574298_2 supporting the notion that the suppressive effect of let-7b/c was dependent on hur binding to c-myc mrna, the enhanced interaction of c-myc mrna with ago2 in the let-7b/c group was abrogated if hur was silenced . 25232020_1 luciferase reporter assay demonstrated that mir-139-5p significantly suppressed the expression of a luciferase reporter gene fused to 3- -untranslated region of pgrmc1, which could be reversed by further introduction of mir-139-5p inhibitor in the kgn cells and rat gcs . 25232020_2 deletion of mir-139-5p attenuated the promotive effect of ha on the expression of pgrmc1 . 22273691_1 bioinformatic prediction showed that the 3'-utr of mmp-13 mrna contained a potential binding mirna-140 site and luciferase mrna fused with 3'-utr of mmp-13 mrna was shown to be repressed by mirna-140 in reporter assays. 22273691_2 fig. 2 mmp-13 is a target of mirna-140 posttranscriptional repression. 22273691_3 these data suggested that the mmp-13 mrna was a target of mirna-140 mediated post-transcriptional repression in vitro. 26515813_1 collectively, our results suggest that sox7 is a direct target of mir-664. 26515813_2 sox7 is a direct target of mir-664 in os cells. 26515813_3 these data confirmed that mir-664 promoted osteosarcoma cells migration and invasion by repressing endogenous sox7 expression and that sox7 plays important role in mir-664-mediated osteosarcoma cell migration and invasion. 21324893_1 we confirmed that increased expression of mir-206 and mir-29 resulted in the translational repression of hdac4 in the presence or absence of tgf--beta via interaction with the hdac4 3'-untranslated region. 21324893_3 consistent with recent reports that mir-206 and mir-29abc targetthe 3'-utr of hdac4. 21324893_4 these data confirm that the hdac4 3'-utr is a target of both mir-29 and mir-206 and, more importantly, demonstrate the ability of these mirnas to potently modulate tgf--beta-induced changes in hdac4 expression. 23158364_1 forced over-expression of mir-23a decreased the expression of uvb-induced topoisomerase-1caspase7stk4 at both the mrna and protein levels, and these effects were reversed by down-regulation of mir-23a. 26449831_1 the result indicates that mir-30a most likely suppresses protein translation through binding sequences at the 3'-utr of runx2. 26449831_2 mir-30a regulated runx2 in os cells. in this study, the mrna and protein expression levels of runx2 were analyzed. 26449831_3 we found that protein translation of runx2 is regulated by mir-30a. 26449831_4 then luciferase assay demonstrated that mir-30a could bind to 3'-utr sites of runx2. 23171948_1 silencing of ampkalpha1 with rna interference inhibited the growth of pancreatic cancer cells in vitro and in vivo and also induced apoptosis, cell-cycle arrest, and inhibited invasion of cancer cells, which is consistent with the effects of mir-148b overexpression. 23171948_2 in conclusion, mir-148b can inhibit cell proliferation, invasion, and enhance chemosensitivity of pancreatic cancer by targeting ampkalpha1. 22653319_1 a decrease in xiap expression and caspase-3 protein levels and an increase in cleaved caspase-3 protein were observed in human ovarian granulosa cells transfected with pre-mir-23a, along with an increased occurrence of apoptosis. 23734217_1 microrna-449a is downregulated in non-small cell lung cancer and inhibits migration and invasion by targeting c-met. 22937097_1 the microcosm and targetscan databases predicted that mir-124a and mir-181a would target dlx5 and msx2, respectively. 22937097_2 the putative binding sites of mir-124a and mir-181a are the 3'-utrs of dlx5 and msx2 mrnas, respectively. 22937097_3 this was performed with a reporter plasmid, into which the wild-type or mutant-type 3'-utr binding sequences of the respective seed regions of mir-124a and mir-181a from dlx5 and msx2 were cloned into the 3'-utr of a luciferase gene . 22629385_1 this analysis pinpointed mir-204, mir-211, and mir-379 as such key regulators. 22629385_3 we performed luciferase reporter assays to determine whether mir-204, -211, or -379 inhibit the expression of the luciferase reporter gene by binding to the il11 3'-utr sequence. 22629385_4 mir-211 and -379 inhibited the reporter activity of both of the constructs, indicating that they bindto at least two sites in the il11 3'-utr . 26408183_1 interestingly, there was significant inversed correlation between mir-346 and srcin1 in cscc tissues. 26408183_2 the 3- -untranslated region of srcin1 mrna contains a putative site partially complementary to mir-346. 26408183_3 quantitative real-time pcr analysis demonstrated the successful overexpression of mir-346 by transfected mir-346 mimic in a431 cells,overexpression of mir-346 inhibited the luciferase activity of the wt reporter plasmid. 26408183_4 upregulation of mir-346 inhibited the mrna and protein expression of srcin1. 26408183_5 srcin1 overexpression reduced the mir-346-induced a431 cell migration. 26227059_1 the 3'-utr of smad1 mrna contains putative binding sites for mir-345 . 26227059_2 we cloned the human smad1 3'-utr into a luciferase reporter plasmid and cotransfected it with mir-345 into lncap and pc-3m cells. 26227059_3 these findings indicate that mir-345 negatively regulates smad1 expression by directly binding to its 3'-utr. 23510267_1 these data demonstrate that bovine mstn is a specific target of mir-27b and that mirnas contribute to explain additive phenotypic hypertrophy in piedmontese cattle selected for the mstn gene mutation, possibly outlining a more precise genetic signature able to elucidate differences in muscle conformation. 23510267_2 co-transfection of pre-mir-142 with the wild-type mstn 3' -utr construct did not alter the luciferase activity, indicating that mir-27b specifically targeted mstn . 23510267_3 here we demonstrate that mstn is further regulated at post-transcriptional level by mir-27b. 26036635_1 these data suggested that mir-32 targeted aurka and that tanshinones suppressed aurka by regulating the expression levels of mir-32 and other interrelated mirnas. 26036635_2 tanshinone suppresses aurka partly through up-regulating the expression of mir-32. 24790587_1 hif-1 alpha had pivotal effects on downregulation of mir-210 decreasing viability and inducing apoptosis in hypoxic chondrocytes. 7999082_1 we used reverse transcription-polymerase chain reaction and northern hybridization to determine the presence of bfgf and its antisense rna in unfertilized human oocytes and postnatal differentiated tissues. 26549292_1 in addition, znrf3 was identified as the target gene of mir-146b-5p in osteosarcoma. 26549292_2 all these results indicate mir-146b-5p and its downstream target gene znrf3 can be used to treat osteosarcoma chemoresistance in the future. 26549292_3 in conclusion, our investigation revealed that the mir-146b-5p affects migration, invasion and chemoresistance in osteosarcoma possibly via downregulation of znrf3. 24902663_1 pdcd4 was selected for further experimental validation, because the complementary sequence of mir-21 was identified in the 3'-utr of pdcd4 mrna by miranda analysis. 24902663_2 moreover cotransfection of 786-o cells with the wt 3'-utr and anti-mir-21 reversed the decrease caused by mir-21 . 24902663_4 expression of pdcd4 was significantly reduced by mir-21 transfection and increased by anti-mir-21 transfection , indicating that mir-21 causes a reduction in pdcd4 expression in 786-o cells. 19703993_1 mir-200a was found to directly targetbeta-catenin mrna, thereby inhibiting its translation and blocking wnt/beta-catenin signaling, which is frequently involved in cancer. 19703993_2 interestingly, we found that increased levels of mir-200a in meningioma cells significantly downregulated -beta-catenin at both mrna and protein levels . 19703993_3 these data strongly suggest that the reduced -beta-catenin levels in pre-mir-200a-transfected cells is a result of direct targeting of the -beta-catenin rna by mir-200a. 19703993_4 taken together, these data suggest that among mir-200a target, the -beta-catenin mrna is one of the major contributors to mir-200a-induced apoptosis. 23861446_1 thus, mir-7a directly targets the scn2b 3- utr in a sequence-specific manner. 23861446_2 moreover, the mir-7a-binding site is well conserved among mammals , indicating scn2b regulation by mir-7a is functionally important. 19723635_1 mir-206 target and regulates human notch3. 19723635_2 hela cells had minimal endogenous mir-206 expression, which provided a good in vitro cell model system to determine a real interaction between exogenously expressed mir-206 and notch3 and should exclude effects from endogenous mir-206. 19723635_3 next, we determined the inhibitory effect of mir-206 on endogenous human notch3 protein expression using hela cells. 19723635_4 as expected, ectopic expression of mir-206 resulted in a significant reduction of human notch3 protein expression . in addition, the level of human notch3 mrna was also repressed by mir-206 . 19723635_5 overall, the above results identified notch3 as a novel targetgene of mir-206. 26160756_1 transfection of huh-7 cells with mir-1275 suppressed igf2bps expression and all three igf2bps were confirmed as targets of mir-1275. 26160756_2 ectopic expression of mir-1275 and knockdown of igf2bps inhibited malignant cell behaviors, and also reduced igf1r protein and mrna. 26160756_3 finally igf1r was validated as a direct target of mir-1275. 26160756_4 these findings indicate that the tumor-suppressor mir-1275 can control hcc tumor growth partially through simultaneously regulating the oncogenic igf2bps and igf1r. 26160756_5 these findings indicate that mir-1275 directly binds to the 3' utr of igf1r. 23485012_1 the serine/threonine kinase mst1, an amplifier of cell apoptosis, seemed to be a target of mir-138, and the activation of the akt pathway was necessary for the anti-apoptotic effect of mir-138. 23485012_2 a marked increase in akt phosphorylation at ser 473 was found in pasmcs overexpressing mir-138, which was blocked by co-transfection with amo-138 , suggesting that mir-138 activates akt signalling by negatively regulating mst1 at the post-transcriptional level. 23485012_3 these data strongly suggest that the akt signalling pathway is involved in the suppression of pasmc apoptosis by mir-138. 23485012_4 these data thus suggest that the mir-138-mediated suppression of caspase-dependent apoptosis appears to target at mst1. 21707582_1 mir203 is a tumour suppressor microrna inhibiting cellular proliferation by targeting creb1 mrna in mm. 21707582_2 creb1 was a common targetpredicted by both of these algorithms, showing an exact match from position 3- 13 of the mature mir203 to the 3'-utr of creb1 mrna . in contrast, the luciferase activity of mutant creb1 3- utr construct, with four point mutations introduced to the putative binding site of mir203, showed comparable activity signals with or without mir203 overexpression, suggesting the direct regulation of mir203 on the creb1 3'-utr . 21707582_3 finally, upon overexpression of precursor mir203, kms-12-pe and wl-2 showed 20% inhibition of cell proliferation as compared with the negative control precursors at 72 h by mtt assay, thereby suggesting that mir203 inhibited proliferation of myeloma cells via targeting creb1 . 21802413_1 under inhibition of pi3 kinase by ly294002, the suppressive effect of mir-491 on hcv replication was abolished, indicating that suppression of hcv replication by mir-491 was dependent on the pi3 kinase/akt pathway. 26555189_1 taken together, our results indicate that mir-30a regulates the immunosuppressive function of mscs by targeting tab3. 19011694_1 experimental validation revealed that mir-22 regulated ppara and bmp7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. 19011694_2 inhibition of mir-22 in osteoarthritic chondrocytes by antisense mir-22 treatment, highly up-regulated bmp-7 and ppara expression, suggesting that mir-22 is a strong regulator of bmp-7 and ppara proteins. 19011694_3 all above data suggest that mir-22 regulates bmp-7 at the mrna level and ppara at the protein level . 20507594_1 we report here that bace1-antisense prevents mirna-induced repression of bace1 mrna by masking the binding site for mir-485-5p. 20507594_2 indeed, mir-485-5p and bace1-antisense compete for binding within the same region in the open reading frame of the bace1 mrna. 20507594_3 our results indicate that mirna-binding sites in the coding parts of mrnas may still be functional and further suggest the possibility of in vivo interactions between mir-485-5p and mature bace1 mrna. 20507594_4 simultaneous over-expression of both bace1-as and mir-485-5p returned the bace1 protein level to the basal level. 20507594_5 these data imply that mir-485-5p and bace1-as may compete for binding to bace1 mrna and support the novel regulatory role of masking a mirna-binding site in bace1 by the non-coding bace1-as transcript. 20507594_6 the high concentration of mir-485-5p and bace1-as in the brain regions suggests the likelihood of their functional interaction with the bace1 mrna targetsite, and involvement in bace1 regulation. 26446987_1 mechanistically, we showed that tat synergized with k1 to induce the expression of mir-891a-5p, which directly targeted ikappabalpha 3' untranslated region, leading to nf-kappab activation. 26446987_2 consequently, inhibition of mir-891a-5p increased ikappabalpha level, prevented nuclear translocation of nf-kappab p65 and ultimately suppressed the synergistic effect of tat- and k1-induced angiogenesis. 26446987_3 our results illustrate that, by targeting ikappabalpha to activate the nf-kappab pathway, mir-891a-5p mediates tat and k1 synergistic induction of angiogenesis. 26446987_4 these data suggest that mir-891a-5p directly targets ikappabalpha. 26446987_5 together these data suggest that mir-891a-5p mediates k1- and tat-induced angiogenesis by targeting ikappabalpha to activate the nf-kappab pathway. 26364844_1 mir-221 and mir-222 can bind the same sequence of reck 3'utr, thereby modulating its expression. 26364844_2 through simultaneous regulation over reck, mir-221 and mir-222 can promote gastric cancer cell growth and invasion. 26364844_3 these results suggest that both mir-221 and mir-222 directly target reck and regulate its expression. 26850728_1 collectively, these results indicated that mir-320a could directly target aqp1 and their interactions would be further verified in a rat ir model. 26850728_3 we have identified that mir-320a directly and functionally modulated aqp1 expression in both in vitro and in vivo conditions. 9774349_2 in this study, we carried out deletion analysis which showed that separate domains of the oxys rna are required for the regulation of fhla and rpos. 9774349_3 we examined oxys repression of fhla and found that the rna inhibits ribosome binding and translation by pairing with a short sequence overlapping the fhla ribosome-binding site. 25312821_1 mir-429 directly targeted notch1 and reduced both mrna and protein levels of notch1 which stimulated proliferation and suppressed apoptosis in hcc cells. 21446014_1 this study also shows that pdef expression is regulated via a functional microrna-204 binding site within the 3'utr. 21446014_2 reciprocal knockdown of endogenous mir-204 levels was performed using antisense oligoribonucleotides targeted against mir-204 in pc3 and du145 cells and resulted in an increase in pdef protein levels, while the pdef mrna levels remained unchanged . 21446014_3 these results demonstrate that mir-204 regulates endogenous pdef mrna at the post-transcriptional level, most likely through a mechanism of translation inhibition. 25575817_1 the mrna and protein levels of pdcd4 were decreased with mir-21 mimics and increased with mir-21 inhibitor treatment . 25575817_2 therefore mir-21 decreased pdcd4 expression in k562 and hl60 cells. 25575817_3 transfection with rbp2 expression plasmid increased mrna and protein levels of pdcd4, and mir-21 mimic treatment reversed the rbp2-overexpression-induced pdcd4 , which suggests that rbp2 increased pdcd4 expression via mir-21. 22144583_1 the sirnas significantly reduced levels of their targetproteins after 24 h, and transfection of mir-200c mimic also led to a significant reduction in both fhod1 and ppm1f protein levels within the same time frame . 22144583_2 conversely, inhibition of mir-200bc/429 cluster mirnas in mcf-7 cells by transfection of microrna hairpin inhibitors increased fhod1 and ppm1f protein levels. 22144583_3 these findings were also validated at the mrna level upon mir-200c overexpression or inhibition , confirming mrna degradation mechanisms for mir-200c targeting of these two genes. 22144583_4 in conclusion, the results of the luciferase assay confirmed that fhod1 and ppm1f are indeed novel direct target of mir-200c. 22144583_5 this suggests that mir-200c might also contribute to the regulation of fhod1 and ppm1f in breast cancer patients. 22144583_6 altogether, these data suggest that targeting of either fhod1 or ppm1f by mir-200c contributes to the effects of mir-200c on migration-related processes. 22438923_1 here we demonstrate that mir-148a and mir-152 down-regulate hla-g expression by binding its 3'utr and that this down-regulation of hla-g affects lilrb1 recognition and consequently, abolishes the lilrb1-mediated inhibition of nk cell killing. 22438923_2 mir-148a and mir-152 potentially targetthe 3'-utr of hla-g. 22438923_3 thus, both mir-148 and mir-152 directly targetthe 3- utr of hla-g and such targeting lead to hla-g down-regulation. 22438923_4 these results indicate that the predicted binding sites were indeed targeted by both mir-148a and mir-152 and that the g/c polymorphism has no influence on mirna-mediated targeting, despite the unusual seed match. 26752466_1 these results clearly suggest that nod2 is controlled by mir-320. 26752466_2 nod2 is a target of mir-320 family. 26752466_3 these results show that mir-320 a, -b, and -c control nod2 expression. 26752466_4 these results suggest that the downregulation of endogenous mir-320 during inflammation is accountable of the nod2 increased expression. 26752466_5 these results show that, during inflammation, exogenous mir-320 are able to control nod2 expression. 24969479_1 as a result, we conclude that mir-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. 24969479_2 to our knowledge, this is the first study related to the expression levels of caspase-3 and mir-221 in different cell lines at the same time. 24969479_3 we expect that our study might pave the way for better understanding the role of mir-221 in apoptotic regulation of caspase-3. 22139076_1 here we report that glia-enriched mir-135a, a microrna that is dramatically downregulated in malignant glioma and correlated with the pathological grading, is capable of inducing mitochondria-dependent apoptosis of malignant glioma by regulating various genes including stat6, smad5 and bmpr2, as well as affecting the signaling pathway downstream. 25053708_1 next, we looked for predicted mir-35 family target genes that might play a role in hermaphrodite fecundity downstream of mir-35-41. 25053708_3 multiple 3- utrs have been annotated for the sup-26 mrna , only one of which contains the mir-35 family target site . 25053708_4 for sup-26 to be a direct mir-35 family target, the longest 1146-bp 3- utr must be used. 25053708_5 sup-26 also suppressed the appearance of endomitotic oocytes in mir-35-41 ;sup-26 . 25053708_6 only 6.8% of uteri in mir-35-41 ;sup-26 contained endomitotic oocytes on the first day of gravidity , compared with 47.8% in mir-35-41 . 25053708_7 therefore, the predicted mir-35 family target gene sup-26 functions downstream of mir-35-41 in regulating spermatogenesis at restrictive temperature. 26747707_1 expression of enforced mir-31 significantly enhanced invasion and migration of multiple pancreatic cancer cells resulting from activation of rhoa through regulation of the mir-31 target gene rasa1. 26747707_2 in addition, our data demonstrate mir-31 enhances invasion-migration of pancreatic cancer cells through its target gene rasa1 and subsequent activation of rho. 26747707_3 ollectively, our results confirm that mir-31 regulates rasa1 in pdac cells. 25822980_2 the increased expression level in all the three mir160 target genes suggests that mir160 is affected in the atttp-oe line. 26265120_1 we screened the targets of mir-155 using targetscan and mirecords, and rab6a was predicted as a putative mir-155 target gene. 26265120_3 these results suggested that mir-155 targets the predicted site in the rab6a gene.thus, 26265120_4 we identified sirt1 as a novel target of mir-155. 26265120_5 these findings suggested that mir-155 suppresses rab6a through degradation of mrna.the 26265120_6 overexpression of mir-155 can partly reduce lps-induced tnf secretion via targeting rab6a. 26717044_1 figure 2: mir-199a-5p negatively regulates map3k11 expression in human esophageal cell lines. 26717044_2 the stability curve in figure 3d demonstrates enhanced stability of map3k11 mrna following silencing of mir-199a-5p in heso cells. 26717044_3 figure 5: contribution of potential mir-199a-5p binding sites in map3k11 mrna. 26646011_1 last, we validated in human hepatoma cells that both mir-21 and mir-27 significantly repress cholesterol synthesis and that mir-27 does so inpart through regulation of the gene that codes for the rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl-coenzymea reductase . 26646011_2 fourth, we validated through cell-based assays that mir-27, which is prominently dysregulated in both chb and chc as well as in hcc, significantly represses cholesterol synthesis inpart through regulation of the gene that codes for the rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase . 26646011_3 furthermore, we demonstrated that the effect of mir-27 is mediated in part through direct regulation of the hmgcr gene, which encodes the rate-limiting enzyme in cholesterol biosynthesis. 26471185_1 taken together, these data support the bioinformatics predictions indicating fos and met 3'-utrs as direct targets of mir-449a. 20676106_1 rnahybrid16 modeling of the 3'-untranslated regions of these potential targets revealed that only the top candidate-擱asa1, encoding p120rasgap -攈ad more than one predicted mir-132 binding site in its 3'-utr. 20676106_2 rnahybrid modeling of the rasa1 3'-utr predicted two mir-132 binding sites, separated by 40 bases . 20676106_3 accordingly, ectopic expression of mir-132 suppressed a luciferase reporter upstream of a 70-bp region of the rasa1 3'-utr . 20676106_4 furthermore, knockdown of mir-132 with an anti-搈ir-132 markedly increased p120rasgap levels in vitro in huvecs and in vivo during bfgf-induced angiogenesis in subcutaneous matrigel implants in mice . 26498766_1 the luciferase activitywas significantly reduced in mir-33a transfected cells compared with that in control cells, suggesting that mir-33a targeted arcn1 3'-utr. 26498766_2 the data showed that the level of endogenous arcn1 in hela cells was obvious lower than that in 293t and a549 cells while the amountof mir-33a in hela cellsis significantly higher than that in the other two cell lines , indicating that the levels of arcn1 and mir-33a are negatively correlated. 26498766_3 taken together, these results indicated that mir-33a repressed endogenous arcn1 expression by directly targeting 3'-utr of arcn1 mrna. 26893720_2 these findings indicate that mir-126 negatively mediates the protein expression of irs1 through its direct binding to the seed sequences in the 3'-utr in irs1 mrna. 23979421_1 it was indicated in transient transfection assay that mir-bart15 could suppress cell growth and induced early apoptosis in ags gastric carcinoma cell in part through targeting the bruce gene. 26898455_1 results showed that the expression of lin28 increased in ccl18-treated mda-mb- 231 and mcf-7 cells while let-7a significantly downregulated lin28 expression . 22660635_1 in turn, mir-23b suppresses il-17-, tumor necrosis factor alpha - or il-1-beta-induced nf-kappab activation and inflammatory cytokine expression by targeting tgf--beta-activated kinase 1/map3k7 binding protein 2 , tab3 and inhibitor of nuclear factor kappa-b kinase subunit alpha and, consequently, represses autoimmune inflammation. 22660635_2 figure 6 tab2 and tab3 are functional targets of mir-23b. 22660635_3 subsequent injection of mice with lentiviruses encoding tab2 or tab3 containing mutated mir-23b target sites markedly reduced the mir-23b-mediated suppression of cia , suggesting that tab2 and tab3 are key targets of mir-23b in vivo and contribute to the beneficial effects of mir-23b in mouse models of autoimmune disease. 26709120_1 wnt10b was previously proved to be the direct target of mir-148a and our result of luciferase reporter assay also confirmed it. 26709120_3 as shown in figure 3, a negative correlation was observed between wnt10b level and mir-148a expression. 26709120_4 furthermore, mir-148a decreased the expression of wnt10b in cafs, and anti-mir-148a increased wnt10b in nfs. 25428378_1 in addition, aeg-1/mtdh was a direct target of mir-145, and the expression of aeg-1/mtdh was inversely correlated with mir-145 expression in nsclc tissues. 25428378_3 these data suggest that mir-145 might induce the degradation of aeg-1/mtdh mrna, leading to a reduction in levels of aeg-1/mtdh protein and implying that aeg-1/mtdh is a direct target of mir-145. in this study, we identified that aeg-1/mtdh was upregulated and was negatively related to mir-145 levels in nsclc. in conclusion, we have reported the altered expression of mir-145 in nsclc cell lines and have shown that mir-145 could modulate cell proliferation and invasion by targeting aeg-1/mtdh. 26544868_1 relevant luciferase+3'-utr expression studies confirmed a direct interaction between hsa-mir-125b and erbb2 and between hsa-mir-22 and pten. 26544868_2 moreover, luciferase+3'-utr constructs validated a direct interaction between mir-125b binding to erbb2 with the identification of a second binding site . 26544868_3 fig 4. validation of mir-125b and mir-22 binding to the 3'-utr of erbb2 and pten respectively. 24486548_2 taken together, our results suggest that mir-503 regulates the resistance of non-small cell lung cancer cells to cisplatin at least in part by targeting fanca. 19521018_2 overexpression of mir-1 decreased the protein amounts of cdk9 without affecting the mrna levels, indicating that mir-1 post-transcriptionally inhibits cdk9 translation. 19521018_3 mir-1 and mir-133 may play significant roles in the myocardial differentiation of mousees cells, and cdk9 may be involved in this process as a target of mir-1. 19521018_4 these results indicate that mir-1 post-transcriptionally inhibits cdk9 translation by targeting the 3- utr of cdk9 mrna in es cells. 26829217_1 cyclin e1 mrna is a mir-15/16 target in the oocyte 15950772_1 we report here the robust expression in the vp-mcns of an rna, which we designate apeg3 that is transcribed in the antisense direction to the 3' untranslated region of the peg3 gene. 15950772_4 the apparently much greater expression of the apeg3 versus the peg3 in the hypothalamus is consistent with the very intense expression of apeg3 versus peg3 in the hns system in ishh . 15950772_5 quantification of the apeg3 to peg3 mrna levels in the son under the conditions in fig. 5 shows that the apeg3 mrna is two- to threefold greater than the peg3 mrna .since the principal function of the mcns in the hns is to respond to systemic osmotic changes, we investigated whether the gene expression of peg 3 and apeg3 in the son was similarly regulated by an osmotic challenge. 20305651_1 moreover, mir-151 exerts this function by directly targeting rhogdia, a putative metastasis suppressor in hcc, thus leading to the activation of rac1, cdc42 and rho gtpases. 20305651_2 mir-151 can downregulate rhogdia expression by targeting its 3' utr. 20305651_3 mir-151 decreased the relative luciferase activities with the wild-type 3' utr of rhogdia. in particular, mir-151-5p, but not mir-151-3p, contributed to this effect . 20305651_4 furthermore, knockdown of rhogdia rescued the inhibitory effects of mir-151-5p inhibitors on hcc cell migration and invasion . 20305651_5 these findings indicate that rhogdia is indeed a functional target for mir-151. 25318608_1 microrna-126 attenuates palmitate-induced apoptosis by targeting traf7 in huvecs 23750239_1 mcl-1, an anti-apoptotic member of the bcl-2 family, as novel targets of mir-26a was found to be in reverse correlation with ectopic expression of mir-26a and knockdown of mcl-1 phenocopied the effect of mir-26a in breast cancer cell lines. 23750239_2 it was further explored that mir-26a increased sensitivity of breast cancer cells to paclitaxel in which mcl-1 was involved. 23750239_3 thus, mir-26a impacts on cell proliferation and migration of breast cancer by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of mcl-1. 23750239_5 7b, the level of mcl-1 protein was significantly down-regulated by the combination treatment of mir-26a and paclitaxel, as compared with paclitaxel alone. 20148895_1 amo-mir-21 sensitized leukemic k562 cells to ato by inducing apoptosis partially due to its up-regulation of pdcd4 protein level. 19597470_4 bioinformatics analyses reveal a conserved target site for mir-330 in the 3'-untranslated region of e2f1 at nucleotides 1018-1024. 19597470_7 in addition, the expression level of mir-330 and e2f1 was inversely correlated in cell lines and prostate cancer specimens. 19597470_8 after overexpressing of mir-330 in pc-3 cells, cell growth was suppressed by reducing e2f1-mediated akt phosphorylation and thereby inducing apoptosis. 19597470_9 collectively, this is the first study to show that e2f1 is negatively regulated by mir-330 and also show that mir-330 induces apoptosis in prostate cancer cells through e2f1-mediated suppression of akt phosphorylation. 18987025_1 mir-126 directly repressed expression of the pik3r2-encoded p85-beta subunit of pi3 kinase in co-transfection assays, whereas p85-beta protein was increased in both primary mir-126螖/螖 endothelium and mir-126 knockdown huvec . 18987025_2 mechanistically, this cell-autonomous action allows mir-126 deficiency to derepress and overexpress the p85-beta regulatory subunit of pi3k and spred1, which represent negative regulators of pi3k and map kinase signaling, respectively . 20863894_1 mir-15/16 targeting bcl2 and mcl1 and dleu7 targeting tnf pathway were proposed as tumor suppressors at 13q14, a commonly deleted region in indolent cll. to determine possible mechanism of mir-15/16 tumor suppressor function, subsequent study examined expression levels of mir-15/16 and bcl2 in cll . 20863894_2 these results showed that mir-15a and mir-16-1 expression is inversely correlated to bcl2 expression in cll and that both micrornas negatively regulate bcl2 at a posttranscriptional level . 26893673_1 in conclusion, the current study demonstrates that mir-96 targets and downregulates samd9 in nsclc, which decreases cisplatin-induced apoptosis and induces cisplatin chemoresistance in nsclc cells. 26893673_3 1a, among the mirnas tested, only mir- 96 significantly decreased the luciferase activity , suggesting that mir-96 targeted samd9. 26893673_4 the aim of the current study was to identify mirnas that regulate samd9 expression, and the results revealed that mir-96 directly targets and downregulates samd9 in nsclc. 26210448_1 in the present study, we firstly identified that the navigator-3 gene as a novel direct target of mir-21. 26210448_2 knock-down of nav-3 using shrna can rescue the effects of anti-mir-21 inhibitor in hcc cell lines, whereas re-expression of mir-21 using transfection with mir-21 mimics phenocopied the nav-3 knock-down model. 26210448_3 additionally, mir-21 levels inversely correlated with nav-3 both in hcc cells and tissues. 26210448_5 together, our findings suggest an important role for mir-21 in the progression of hcc, which negatively regulated navigator-3 in the migration of hcc. 26225959_1 here we showed that mir-198 directly bound to the 3'-utr of ccnd2 mrna, which was a key regulator in cell cycle progression. 26225959_2 overexpressed mir-198 repressed ccnd2 expression at mrna and protein levels and subsequently led to cell proliferation inhibition and cell cycle arrest in the g1 phase. 26225959_3 figure 2. mir-198 directly bound to the 3'-utr of ccnd2 mrna. 21781967_1 in this study, we found that mir-19b, a member of mir-17-92, was highly expressed in the pancreatic progenitor cells, and mir-19b could targetthe 3' utr of neurod1 mrna to decrease its protein and mrna levels. 21781967_3 2.identification of neurod1 as the targetgene of mir-19b. 21781967_4 also, qrt-pcr results showed that overexpression of mir-19b decreased neurod1 mrna level . 21781967_5 western blotting results showed that the neurod1 protein was significantly inhibited by mir-19b . 21781967_6 mir-19b decreased insulin 1 expression via negative regulation of neurod1. 17942906_1 regulation of myc mrna by let-7a was confirmed by transfections with pre-let-7a. 17942906_2 overexpression of let-7a decreased myc mrna and protein . 26898430_1 the real-time pcr results showed that lncrna meg3 was down-regulated, while mir-140-5p was up-regulated in epcs of patients with mets. the relative meg3 expression was significantly decreased and mir-140-5p expression was markedly increased. 26898430_2 the overexpression of meg3 resulted in the downregulation of mir-140-5p expression level in a dose-dependent manner, and also caused up-regulation of hdac7 level. 22012804_1 to verify the targeting of endogenous zeb1 and zeb2 by the mir-200 family in tubular epithelial cells, western blot analysis of the protein expression levels of zeb1 and zeb2 in nrk-52e cells after transfection with mir-200 family mimics or inhibitors was performed. 22012804_3 7a, overexpression of each of the mir-200 family members by transfection of their mimics significantly suppressed the expression of zeb1 and zeb2. 22012804_4 meanwhile, the protein expression of zeb1 and zeb2 was significantly increased after downregulation of the mir-200 family by transfection of their inhibitors . 22012804_5 thus we hypothesized that the mir-200 family regulated tubular emt through reducing the expression of the transcriptional repressor of e-cadherin by targeting zeb1 and zeb2. 24755562_1 overexpression of mir-17-5p into paclitaxel resistant lungcancer cells reduced beclin1 expression and a concordant decease in cellularautophagy. 22545159_1 we used an in silico approach to identify lin28 as a target of mir-125b, and validated this interaction using mir-125b knockdown. 22545159_3 we now demonstrate a role for mir-125b in promoting the differentiation of mesoderm including cms from hescs, and that this likely occurs in part through mir-125b targeting of the pluripotency factor, lin28. 23916944_1 in pancreatic cancer cells, reduced levels of the mirna mir-23b increase levels of atg12 and autophagy to promote radioresistance. 23325891_1 mir-223 has been shown to target igf1r . 23325891_3 to determine whether the up-regulation of igf1 receptor was responsible for the increased proliferation seen in eosinophil cultures derived from the mir-223-/- mice, we treated eosinophil cultures on day 8 with 2 μm of an igf1 receptor inhibitor - picropodophyllin or an equivalent volume of dmso as a control. 23619095_1 loss of autophagy activity suppresses developmental defects caused by partially impaired silencing of mirna targets including the let-7 family and lsy-6. 23619095_3 thus, autophagy activity modulates mirna-mediated gene silencing and degrades a core mirisc component. 17252019_1 these results suggest that the complementary site in the e2f3 mrna is a target of mir-34a-mediated post-transcriptional gene silencing. 17252019_2 western blot analysis of sk-n-as cells transfected with mir-34a showed a signifcant reduction in e2f3 protein in cells overexpressing mir-34a, confirming that mir-34a target e2f3 mrna . 17252019_3 neither the construct containing the putative mycn targetsequence or a 625 bp fragment of the 3-utr showed a reduction in luciferase activity, indicating that mycn is not a direct target of mir-34a. 17404574_1 mcl-1 protein expression can be regulated by mir-29b. 17404574_2 enforced mir-29b expression reduced mcl-1 cellular protein levels and sensitized the cancer cells to tumor necrosis factor-related apoptosisinducing ligand cytotoxicity. 17404574_4 thus mir-29 is an endogenous regulator ofm cl-1 protein expression, and thereby, apoptosis. 16224024_4 slitrk1 mrna and hsa-mir-189 showed an overlapping expression pattern in brain regions previously implicated in ts. 25246801_2 further, k-ras was confirmed as a direct target of mir-206 by using luciferase reporter assay. 26843615_1 the dual-luciferase reporter assay indicated that mir-490-3p directly targeted tgfalpha by binding its 3- untranslated region. 26843615_2 mir-490-3p downregulated tgfalpha expression in tumor xenografts in vivo. 26843615_3 besides, we found that mir-490-3p overexpression target tgfalpha in endometrial carcinoma. 26352673_1 figure 7 sox4 is a direct target of mir-132. 26352673_3 our results clearly demonstrated that mir-132 inhibited cell proliferation, invasion and emt in osteosarcoma cells by downregulation of sox4, and that knockdown of sox4 was essential for the mir-132-inhibited cell proliferation, invasion and emt in osteosarcoma cells. 25529604_2 moreover, we found that the expression level of wnt1 was suppressed significantly by mir-139-5p, which triggered inhibition of wnt/-beta-catenin signaling through upregulation of glycogen synthase kinase 3 beta and downregulation of p-gsk-3-beta , -beta-catenin , and nuclear -beta-catenin . 20837903_1 taken together, these results demonstrate that efna3, ptp1b, dapk1, and ctgf are the target genes of mir-210. 20837903_2 figure 5b shows that efna3, ptp1b, dapk1, and ctgf were significantly enriched in immunoprecipitates of mir-210-overexpressing cells compared with cells transfected with a scramble sequence . 20837903_3 we concluded that efna3, ptp1b, dapk1, and ctgf are all associated with mir-210 loaded risc complexes and hence they are the real targets of mir-210. 26707641_1 setd8 was identified as a direct target of mir-127-3p, and setd8 expression decreased post mir-127-3p overexpression, while setd8 overexpression could reverse the potential influence of mir-127-3p on the migration and invasion of os cells. 26707641_2 mir-127-3p is suggested to act mainly via the suppression of setd8 expression. 26707641_3 these results confirm that setd8 is a direct target of mir-127-3p in os cells. 26129883_1 the 3'-utr of lcn2 was inserted downstream of the luciferase gene and transfected into hl-1 cells together with mirnas mimics or mir-nc. 26129883_3 in order to further proved its reliability, mutants of lcn2 3'-utr was constructed by deleting the mir-138 targets site and co-transfected into hl-1 cells together with mir-138 mimics/mir-nc. 26801671_1 in the present study, we demonstrated that mir-31 only inhibited the cell migration and invasion, as well as the expression of a known mir-31 target oncogene radixin, in u251 glioma cells that expressed low level of p21. 26801671_2 furthermore, analysis for 35 glioma specimens showed that the expression of radixin was negatively correlated with the mir-31 level in glioma tissues with low p21 expression. 26801671_4 4a, b, overexpression of mir-31 significantly decreased the protein levels of radixin in u251 cells that expressed low level of p21, but had no effect on its expression in shg44 cells that expressed high level of p21. 26801671_5 these findings indicate that the expression of the mir-31 target radixin is negatively correlated with the mir-31 level in a p21-dependent manner. 24582749_2 we analyzed the 30-utr of gpr124 and identified one conserved target site for mirna-138-5p located at position 1132- 1139. 26887505_1 mir-4707-5p and mir-4767 promoted apoptosis by targeting and downregulating two apoptosis inhibitors, api5 and bcl2l12, respectively. 26233544_1 we found that the expression level of mir-141 was positively correlated with meg3 expression in both gc and matched nonmalignant tissues. 26233544_2 we also examined the effect of knockdown the e2f3 expression on meg3 expression by sirnas. 26233544_5 we found that e2f3 knockdown induces meg3 expression in gc cells . 26233544_6 these findings suggested that mir-141 could increase meg3 expression through reduction in the expression of e2f3 in vitro. 26233544_7 pearson's correlation coefficient analysis suggested that relative e2f3 expression was inversely correlated with mir-141 and meg3. 25833694_1 furthermore, mir-489 could regulate suz12 as shown by luciferase reporter and western blot assays. 25833694_2 thus, our data indicated that suz12 was a direct target of mir-489. 25833694_3 the results suggested that mir-489 negatively regulated suz12 expression by binding its 3'-utr in lung cancer cell lines. 25833694_4 abnormal expression of mir-489 regulated the cells invasion by binding suz12 3'-utr in vitro. 24560795_1 microrna-125b regulates osteogenic differentiation of mesenchymal stem cells by targeting cbfb in vitro. 24560795_2 it is concluded from the result that mir-125b is a key regulatory factor of osteoblastic differentiation by directly targeting cbfb and indirectly acting on runx2 at an early stage osteoblastic differentiation. 24560795_3 mir-125b targets cbfb by binding 3- utr of cbfb mrna. 24560795_4 taken together, the data suggested that mir-125b could target cbfb by binding complementation within the cbfb mrna 3- utr. 22139839_1 we suggest that mir-155 and mir-125b, which are induced by cd154 and stromal cell signals, contribute to regulating proliferation and that bcl2 is one of their target mrnas. 22139839_2 therefore, mir-155 and mir-125b are able to repress luciferase through action at specific sites on the bcl2 3'-utr. 22139839_3 figure 5.mir-155 and mir-125b repress bcl2 through sites in the bcl2 3'-utr. 22139839_4 therefore, cd154 repression of bcl2 required mir-155 and mir-125b. 22139839_5 we found that bcl2 was repressed to about a third of its basal level by cd154 culture and mir-155 and mir-125b may accomplish most of this effect. 25482044_1 we also found that enforced expression of mir-218 significantly decreased cell proliferation, colony formation, migration and invasion, induced cell apoptosis and arrested the cell cycle in the g0/g1 phase, as well as suppressed tumor growth in a nude mouse model. in addition, our results showed that mir-218 mimics increased the sensitivity to the antitumor effect of cddp in the human eca109 cells. 25482044_2 importantly, this study also showed that mir-218 regulated the expression of phosphorylated pi3k, akt and mtor, which may contribute to suppressed tumor growth of escc and enhanced sensitivity of escc cells. 26452030_1 we found that inhibition of mir-21 substantially increased pten and pdcd4 expression in skbr3 cells,confirming that both proteins are direct targets of mir-21. 26452030_2 furthermore, both pten and pdcd4 protein expression significantly and inversely correlated with the expression of mir-21 in her2-positive breast cancer patients. 22770403_1 microrna-21 expression is up-regulated in human cholangiocarcinoma and pten, pdcd4 are direct effectors of microrna-21. 22770403_2 pten and pdcd4 are bona fide target of microrna-21 in human cholangiocarcinoma. 22770403_5 taken together, these findings indicated the specificity of the interaction between microrna-21 and its targetregions located at the 3'-utrs of pten and pdcd4 mrna. 26335888_1 moreover, we identified that myc mrna was a direct target of mir-34a in jeg-3 cells by dual luciferase reporter assay, and found that downregulation of myc expression by mir-34a targeting significantly reduced the invasiveness of jeg-3 cells. in addition, we identified that myc mrna was a target of mir-34a in jeg-3 cells, and revealed that suppressing of myc expression by mir-34a significantly inhibited jeg-3 invasion. 26335888_2 furthermore, direct binding of mir-34a on the 3'-untranslated region of myc mrna was assessed by dual luciferase reporter assay. 26335888_3 hence, the luciferase assay demonstrated that mir-34a bound directly and specifically to myc 3'-urt and repressed the translation of myc in jeg-3 cells. in summary, the above results suggest that myc promotes trophoblast invasion, while mir-34a inhibits trophoblast invasion by downregulating myc expression via direct targeting on myc transcripts. 24375660_1 forced over-expression of mir-200c decreased the level of bmi1 protein and moreover, over-expression of bmi1 rescued the biological effects of mir-200c, indicating bmi1 is a direct mediator of mir-200c functions. 26080435_2 these data suggest that pca3 binding to prune2 pre-mrna controls prune2 levels. 26080435_3 we confirmed these findings in prostate- and prostate cancer-derived cells, where ectopic pca3 expression induced down-regulation of endogenous prune2 expression. 26045321_1 the current research was designed to delineate the mechanism of mir-138 in regulating psoriasis via targeting runx3. in this study, we found that the expression of runx3 is increased significantly while the expression of mir-138 decreased significantly in cd4 t cells from psoriasis patients. 26045321_2 we found that the inhibition of mir-138 increases runx3 expression and increased the ratio of th1/th2. 26045321_3 furthermore, the mir-138 mimic was transfected into cd4 t cells from psoriasis patients. 26045321_4 the results showed that the overexpression of mir-138 inhibits runx3 expression and decreased the ratio of th1/th2 in cd4 t cells. 24591631_1 interestingly, mir-22, mir-27a,mir-29a, and mir-100 were all moderately down-regulated by either e6 or e7, with mir-22 and mir-27a being slightly more susceptible to e7 than to e6. 23649631_1 forced expression of the mir-23a/24-2/27a cluster promoted mammary carcinoma cell migration, invasion, and hepatic metastasis, through targeting sprouty2 and consequent activation of p44/42 mapk. 23649631_2 epidermal growth factor induced the expression of the transcription factor c-myc, which promoted the expression of mature mir-23a, mir-24-2, and mir-27a and subsequently decreased expression of spry2 and activated p44/42 mapk to promote mammary carcinoma cell migration and invasion. 23649631_3 concordantly, aso to each mirna increased luciferase reporter activity , indicating that the mir-23a/24-2/27a cluster directly targets spry2. 26239725_1 we found that mir-22 was downregulated in liver cancer tissues and cell lines and confirmed that mir-22 directly targeted the gal-9 3'utr and negatively regulated gal-9 expression by luciferase reporter assay and transfection of microrna mimics. in the present study, we found that 4 mirnas were potential regulators of gal-9 and confirmed that mir-22 may directly inhibit gal-9 expression and cause lymphocyte apoptosis and tumor cell proliferation. 26239725_2 luciferase reporter gene assay and detection of gal-9 mrna and protein expression after transfection with the mir-22-mimics confirmed that mir-22 directly targets gal-9 and inhibits the expression of gal-9 via binding to the specific target site in the gal-9 3'utr. 19074828_2 our results indicate that down-regulation of hsa-mir-10a may increase usf2 and contribute to the increase in cell proliferation of cml implicating a mirna in the abnormal behavior of cml. 19074828_3 these results lead us to suggest that hsa-mir-10a down-regulation may cause increased levels of usf2 also in cml cells from patients. 19074828_4 these results indicate that down-regulation of hsa-mir-10a and consequently overexpression of usf2 participate in the abnormal growth of cml cells. 26361218_1 the targetscan algorithms showed that the 3 - -utr of sp1 contained a mir-150-binding site. 26361218_2 the luciferase reporter assay showed that the luciferase activity of mg63 cells that were co-transfected with the 3 - -utr of sp1 and mir-150 mimics decreased compared to the nc group. 26361218_3 the results showed that a significant increase in relative luciferase activity was noted after mutation,suggesting that the mutation in the 3 - -utr mir-150-binding site may disrupt the interaction between mir-150 and the 3 - -utr of sp1 . 26467212_1 here, we confirmed that rb1, an important tumor suppression gene , is a direct target of mir-155 which is directly up-regulated by mcrs1. 26467212_2 these results demonstrated that rb1 is a functional target of mir-155 in nsclc cells. 26467212_3 collectively, these data confirmed that mcrs1 promotes the proliferation of nsclc cells via mir-155 targeting of the rb1 gene. 26467212_4 fourthly, the results of the luciferase reporter assays revealed that mir-155 bound to the 3'-utr of rb1. 26918448_1 these results clearly demonstrated that mir-489 inhibits her2 expression by directly binding to its 3'-utr region. 26572149_1 the dual-luciferase reporter assay also confirmed that mir-25 harbored the a allele which caused an incapacitation of binding at the tob1. 23212916_1 there was a significant decrease in ratio of renilla/firefly luciferase activity in cells transfected with either cdk6 or rictor 3'-utr compared to n.c. 23212916_2 cdk6, rictor, and ctsb proteins were significantly knocked down in cells ectopically expressing mir-218, confirming that these genes are among the true target of mir-218 . 23212916_3 this shows that mir-218 directly binds cdk6 and rictor targetsequences identified by hits-clip . 23212916_4 these data suggest that cdk6 is a functional target of mir-218 in medulloblastoma tumor cells. 25582198_2 further functional studies suggested that repression of irs2 by mir-30a partially mediated the tumor suppressor effect of mir-30a. in addition, mir-30a inhibited constitutive phosphorylation of akt by targeting irs2. 25582198_3 taken together, our study provides the first evidence that mir-30a suppressed colon cancer cell growth through inhibition of irs2. in all, these findings indicate that that mir-30a directly targets the irs2 3- utr, thereby inhibiting irs2 expression. 17608773_1 myc can upregulate the mir-17 cluster by binding directly upstream of the mir-17 locus.deregulation of the mir-17 polycistron can be assumed to contribute to aggressive cancer development by repressing tumor suppressor genes.t-betarii is the direct downstream target of the mir-17 polycistron. 26686902_1 further experiments confirmed that e1a binding protein p300 , a type of histone acetyltransferase important for runx2 activity and stability, was a direct target of mir-132-3p. 26686902_2 this result suggests that ep300 is a direct target of mir-132-3p. 26686902_3 thus, our results demonstrate that mir-132-3p directly targets ep300 and inhibits osteoblast differentiation in part by decreasing ep300 expression, which, in turn, leading to suppression of the synergistic activity and acetylation of runx2. 20049626_1 our results also indicated that mir-16/34a-c, mir-17-5p, mir-125, mir-106, and mir-150 were the upstream factors, which could regulate the expression of bcl-2, e2f1, e2f3, rb1, and p53, respectively. 20049626_2 the results showed that the genes expression may be regulated by mir-16/34a-揷 , mir-17-5p , mir-125 , mir-106/20 , and mir-150 . in order to investigate whether the above genes play an important role in a549 cells proliferation/apoptosis, their expression was estimated after treatment with aso. 25875646_2 these findings suggest that down-regulation of mir-223 promotes degranulation via the pi3k/akt pathway by targeting igf-1r in mast cells. 25875646_4 igf-1r was targeted by mir-223 in this study. 26810534_2 il-6 expression was decreased in the mci without ht group compared with the corresponding mci without ht group and was negatively correlated with the relative expression of let-7f. in addition, we constructed a luciferase reporter plasmid and the psicheck2 vector containing the 3'-utr of il-6 with the binding site of let-7f directly downstream of the luciferase reporter gene. 18458081_1 we experimentally established hcn2 as a targetfor repression by the muscle-specific micrornas mir-1 and mir-133 and established hcn4 as a targetfor mir-1 only. 18458081_2 we conclude that down-regulation of mir-1 and mir-133 expression contributes to the re-expression of hcn2/hcn4, and thereby the electrical remodeling process in hypertrophic hearts. 18458081_3 co-application of mir-1 with amo-1 or mir-133 with amo-133 eliminated the silencing effects on luciferase reporter activities. 18458081_4 mir-1 elicited significant repression on luciferase activity with the 3'-utr of hcn4 despite the fact that the 3'-utr of hcn4 matches the center portion but not the 5- end of mir-1. 23667173_1 we previously showed that the transcription factors tfap2a and tfap2c are targeted by mir-214 in ma-2 cells ; we now observed relevant tfap2a and tfap2c downmodulation by mir-214 also in wk-mel and sk-mel-28 cells . 23667173_2 these results suggested that mir-214-揹riven alcam upregulation could depend on tfap2a and/or tfap2c decrease due to mir-214 targeting. 23486085_1 our analysis revealed that pik3cd was a potential target of mir-30a. 23486085_2 the 3'-utr of pik3cd mrna contains a complementary site for the seed region of mir-30a. 23486085_3 these results strongly suggest that pik3cd is a direct target of mir-30a in crc cells. 23486085_5 we found that mir-30a directly bound to the 3'-utr of pik3cd, which contains a mir-30a-binding site, by dual-luciferase reporter assay. 23486085_6 moreover, mir-30a overexpression significantly down-regulated pik3cd expression at both mrna and protein levels. 23486085_7 these results suggest that pik3cd may be a target of mir-30a in crc cells. 20453032_1 sibc has two target recognition domains, trd1 and trd2, which function independently. the target site for trd1 is located within the orf of ibsc, whereas the target site for trd2 is located in the translational initiation region. 20453032_5 sibc-ibsc mrna complex, rnase iii-cleavage patterns markedly changed as the concentration of target rna increased, suggesting that interactions between sibc and ibsc promote overall structural changes in rna. 23868745_1 these findings suggested that pgc-1alpha is a direct target gene of mir-130b in muscles. 23868745_2 these results further supported the idea that adipose tissue expression of mir130b might be the main driver of the changes in circulating mir-130b. 23868745_3 mir-130b regulates muscle metabolism by targeting pgc-1alpha. 26704889_1 thirdly, stem cell factor , a mir-34c target, was specifically reduced upon an introduction of e2f1 which lead to suppression of crc cell proliferation. 26704889_2 moreover, we detected some other previously identified mir-34c targets including myb, c-myc, bcl2 and met. 26704889_3 unexpectedly, none of the detected mir-34c targets were negatively regulated by e2f1 as scf was , indicating a possible specific effect of e2f1 on mir-34c-scf axis in crc cells. 26813039_1 mir-199b-5p targeted the 3- utr of klotho. 26813039_2 mir-199b-5p targeted klotho and regulated its expression in hk-2 cells. 26062455_1 these results demonstrated that mir-196a regulated breast cancer cell growth by targeting ube2c. 26062455_3 the levels of ube2c mrna and protein were substantially downregulated by mir-196a inhibitors . 26062455_4 the results demonstrated that ube2c was a direct target of mir-196a and positively regulated by mir-196a in breast cancer cells. 26062455_5 collectively, these results suggested that high endogenous mir-196a targeted and upregulated the expression of ube2c and contributed to the progression of breast cancer. 20525879_1 lin-28b overexpression enhanced the expression of the known let-7 target c-myc and hmga2. of these 111 mirnas, only let-7/mir-98 family members and mir-15a were reduced by >2-fold by lin-28b overexpression . 20525879_2 to elucidate the mechanisms of lin-28b in carcinogenesis, known target of let-7 were evaluated. 20525879_4 large-scale real-time pcr array analysis revealed that, among 380 mirnas, only let-7/mir-98 family members were regulated by lin-28b. 20525879_5 lin-28b overexpression enhanced the expression of the known let-7 target c-myc and hmga2. 24811402_2 we show that in the absence of mir-214, expression of proto-oncogene n-ras is markedly elevated in mir-214 mefs, and manipulations of mir-214 levels using microrna mimics or inhibitor in rd cells reciprocally altered n-ras expression. 24811402_3 we further demonstrate that forced expression of n-ras from a cdna that lacks its 3'-untranslated region neutralized the pro-myogenic and anti-proliferative activities of mir-214. 24811402_4 finally, we show that n-ras is a conserved target of mir-214 in its suppression of xenograft tumor growth, and n-ras expression is up-regulated in xenograft tumor models as well as actual human rms tissue sections. 26646106_1 we identified targeting sites for mir-103 in the 3' -untranslated region of akap12 by bioinformatic analysis and confirm their function by a luciferase reporter gene assay. 26646106_2 we identify mir-103 as a potential repressor of akap12 and demonstrate its ability to promote hcc proliferation by directly targeting the 3 ' untranslated region of akap12. 26646106_3 this finding supports our finding that akap12 is a target of mir-103 . 26646106_4 furthermore, our data shows that by regulating akap12 expression, mir-103 plays an oncogenic role in hepatocarcinogenesis. 21743492_1 as expected, the predicted mir-221 and -222 targets, p27kip1, and pten were expressed at decreased levels in the non-tumorigenic u87mg cells as compared with t98g cells. 21743492_6 western blot analysis of the known mir-221 and -222 targets, pten and p27kip1. 24370341_1 specifically, the constraints on the autophagic flux were associated to the mirna-dependent down-regulation of the lysosome-associated proteins rab27a and lamp3. 24370341_2 these findings suggest that mir-205-mediated impairment of the autophagic pathway may interfere with the detoxifying capabilities of prostate cancer cells in their attempt to cope with cisplatin-induced detrimental effects. 26381333_1 arhgap1, arhgdib and rras are targeted by mir-449 in haecs. 18723524_1 a highly significant decrease in the expression of endogenous grn was observed in m17 cells treated with mir-659 . 18723524_3 we further demonstrate that mir-659 can regulate grn expression in vitro, with mir-659 binding more efficiently to the high risk t-allele of rs5848 resulting in augmented translational inhibition of grn. the stronger binding of mir-659 to the grn mrna containing the t-allele was expected to result in a more efficient inhibition of grn translation leading to reduced grn expression levels. 17699775_1 let-7 negatively regulates the protein levels of cdk6 and cdc25a. 17699775_3 to provide further validation for these cell cycle genes as direct let-7 target, we did reporter assays where we independently fused the 3'-utrs of cdk6 and cdc25a downstream of firefly luciferase . in luciferase assays, both 3'-utrs conferred let-7-揹ependent repression of the reporter gene compared with a negative control anti-mir. 17699775_4 the effect on the cdc25a and cdk6 3'-utrs caused by the anti-搇et-7 was similar to a known let-7 targetgene, nras . 17699775_6 given the close working relationship between cdk6 and cyclin d in promoting the g1 to s transition, and the fact that ccnd2 is the highest scoring cell cycle gene predicted as a let-7 targetby pictar , we also tested the ccnd2 3'-utr in the same assay. 17699775_7 we found a similar result to cdk6 , suggesting that ccnd2 is also a direct target of let-7. 16325577_1 on the contrary, treatment with ra, in addition to inducing c/ebpalpha expression, restored its binding activity and its correct nuclear distribution and increased its transactivation function . 16325577_2 thus, it appears that upregulation of c/ebpalpha by ra precedes mir-223 activation in these cells no significant difference was observed between constructs iii and iv, indicating that the region upstream of the c/ebpalpha sites does not contribute to this induction. 16325577_3 these results indicated that the region containing the c/ebpalpha binding sites is necessary for mir-223 responsiveness to ra. 23188185_2 increased expression level of mirna-22 had effects on rad51 expression after irradiation. 20617180_1 we identified that mir-101 could efficiently targetedna-pkcs and atm via binding to the 3'- utr of dna-pkcs or atm mrna. 20617180_2 these data suggest that mir-101 could suppress the expression of dna-pkcs or atm through the binding sequence at the 3'-utr of dna-pkcs by the strand, mir-101* or at the 3'-utr of atm by the strand, mir-101. 20617180_3 these results indicate for the first time that, besides mtor, dna-pk and atm are also target of mir-101. 18840437_1 we identified mir-183 as a potential metastasis-inhibitor. expression level of mir-183 was reversely correlated with the metastatic potential of lung cancer cells. 18840437_3 mechanistically, we identified vil2-coding-protein ezrin as a bona fide target of mir-183. 21360639_1 mir-16 directly target the zyxin mrna 3'utr. 21360639_2 next, we found that the zyxin mrna level was inversely correlated with mir-16 level . 21360639_4 when mir-16 was blocked by mir-16 aso, the egfp expression level was significantly higher than the aso-nc group. 21360639_6 so we concluded that zyxin was a direct target of mir-16 in hep-2 cells. 21360639_7 consequently, we got similar results with mir-16-blocking assays , suggesting that mir-16 facilitates cell movement by downregulating zyxin gene in laryngeal carcinoma cell line hep-2. 21336967_1 moreover, the enhancement effects of pgp and mir-16 on radiation-induced apoptosis were counteracted by overexpression of bcl-2. 26374840_1 fig. 3. mir-150 directly regulated expression levels of angiogenic target genes cxcr4, dll4, and fzd4 in ecs. 26261546_1 we also confirmed that mir-1228 mimics repressed the expression of moap1, while anti-mir-1228 induced the protein expression of moap1 , which was consistent with previous results illustrating mopa1 was a direct target of mir-1228 . 26261546_3 these results suggested that mir-1228-induced breast cancer cell proliferation, invasion and migration were mediated by moap1 and scai, as illustrated in figure 4g. 26149214_1 over-expression of hsa-mir-1283 reduced the mrna level of atf1 in ha-vsmcs. 26149214_2 in addition, we tested the atf1 mrna levels and found that inhibition of mir-1283 could significantly increase the atf1 mrna level, while over-expression of mir-1283 could reduce the atf1 mrna level to some extent, although the difference was not significant, which suggested that mir-1283 might play a role in the ha-vsmcs through targeting atf1 . 26359920_1 our results indicated that p85alpha is a direct target of mir-29 and is negatively regulated by mir-29b in hepatocytes. 26359920_2 in agreement with the findings in vitro, we found that the expression of mir-29 and the protein levels of p85alpha were inversely correlated in the liver of fasted mice. 26359920_3 fig. 3. mir-29b targets p85 in c57bl/6 mouse primary hepatocytes. 22943841_1 mirna-101 is known to target several tumorpromoting genes such as enhancer of zeste homolog 2 in breast, prostate, hepatocellular, gastric cancers,6-9 but the role of mirna-101 in pdac is not well understood. 22943841_2 fig 4. effect of mir-101 on ezh2 interaction with cdh1 promoter, expression of its transcriptional inhibitors, and effect on global methylation and acetylation. 26801660_1 luciferase reporter assay demonstrated that ei24 was a direct target of mir-483-3p. 26801660_2 collectively, our study demonstrated that mir-483-3p could promote escc progression at least in part through directly targeting ei24, supplying a potential strategy for mirna-based escc therapy. 26801660_4 luciferase reporter assay showed that the fluorescence of ei24 3'-utr-wt transfected with mir-483-3p was downregulated more than 50% compared with the control, and was recovered after mutation on specific site which can be bound by mir-483-3p, indicating that ei24 is a direct target of mir-483-3p. 26780721_1 we found that stat1, a transcription factor involved in th1 differentiation, is a putative target of mir-140-5p predicted by numerous microrna prediction programs. 26780721_2 hek293 cells were transfected with the mimic oligonucleotide of mir-140-5p and the dual luciferase vector conjugated with the stat1 binding sequence at the 3'-utr . 26780721_4 therefore, these results demonstrated that mir-140-5p could specifically bind to stat1. 26780721_5 together, our results demonstrated that stat1 was a functional target of mir-140-5p. 23879965_1 these results suggested that mir-487a negatively regulated the expression of bcrp by directly targeting the 3' utr of bcrp. 26710269_1 interaction between mir-192 or mir-204 and hottip were further confirmed using dual luciferase reporter gene assays. 26710269_2 in the current study, we for the first time identified the negative regulation of lncrna hottip by mir-192 and mir-204 via the argonaute 2 -mediated rnai pathway. 22266859_1 mir-32 was demonstrated to reduce apoptosis, whereas mir-148a enhanced proliferation. 19135651_1 furthermore, we showed that the direct binding of mir-504 to the drd1 3'utr, verified by site-directed mutagenesis, causes a significant expression difference between the two alleles.mir-504 23343715_1 these results indicated that ezh2 was a direct target of mir-138 in nsclc cells. 23343715_2 taken together, these results indicate that mir-138 regulated nsclc cell growth, at least in part, by downregulating ezh2. 23343715_3 together, these results suggest that mir-138 modulates nsclc cell growth, at least inpart, by directly targeting ezh2. in summary, our results identify that mir-138 as a potential tumor suppressor could inhibit cell proliferation, induce cell apoptosis and g0/g1 cell-cycle arrest, by targeting ezh2 in nsclc cells. 23343715_4 moreover, reduced ezh2 protein was confirmed in mir-138-overexpressed tumors by western blotting . 23343715_5 taken together, these results demonstrated that stable overexpression of mir-138 inhibited the tumorigenicity of nsclc cells in the nude mice xenograft model. 23551751_1 human glioma tissues with low expression of mir-139 displayed higher expression of mcl-1 protein than those with high expression, suggesting that low mir-139 contributes to mcl-1 overexpression. 23551751_3 finally, we observed that mcl-1 knockdown resulted in similar effects compared with mir-139 transfection. 23270926_1 when conforming whether mtor is a bona fide target of mir-100, the relative luciferase activity of the reporter containing wild-type mtor 3'-utr was significantly suppressed when mir-100 was cotransfected. in contrast, the luciferase activity of the reporter containing the mutant mir-100-揵inding site was unaffected, indicating that mir-100 may suppress gene expression through mir-100-揵inding sequences at the 3'-utr of mtor. 23270926_2 these results indicate that mir-100 may act as a tumor suppressor through downregulating the expression of mtor in bladder cancer cells. 26132560_1 these results suggest that btg2 is target gene of mir-21 in cardiac myocytes and that mir-21 may protect cardiacmyocytes from dox-induced injury through post-transcriptional regulation of btg2. 26313572_1 luciferase assays revealed the target effects of mir-124 on flotillin-2 expression. 26313572_2 mir-124 downregulated flotillin-2 expression through directly targeting its 3 ' -utr. 26313572_3 these data suggested that the regulation of mir-124 on flotillin-2 depends on the specific seed region sequence. 26313572_4 mir-124 was found to be a negative factor which downregulated the expression of flotillin-2. 26070964_1 we identified mir-383 as a suppressor of robo3, and revealed its expression to be inversely correlated with robo3. 26070964_2 these results suggested that mir-383 regulates robo3 expression both by mrna degradation as well as translational repression. 26070964_3 we provided evidence for robo3'ssuppression by mir-383 and showed that robo3 binds wnt/-beta-catenin pathway inhibitor sfrp1 and activates the wnt/-beta-catenin pathway and expression of emt markers in pancreatic cancer cell lines. 25839659_1 the result of luciferase assay indicated that the 3' -utr of ncx1 was targeted by mir-132. 25839659_3 mir-132 can salvage cardiomyocytes exposed to hypoxia by targeting ncx1. 18521080_2 here, we proved that the cyclin-dependent kinase inhibitor cdkn1c/p57 is also a direct target of mir-221. in conclusion, we suggest that mir-221 has an oncogenic function in hepatocarcinogenesis by targeting cdkn1b/p27 and cdkn1c/p57, hence promoting proliferation by controlling cell-cycle inhibitors. 24967732_1 expressions of erk1/1, raf-1, p38 and jnk in bancr silencing sk-mel-5 cells were detected by western blot. 24967732_2 loss of bancr induced the inactivation of erk1/2, jnk and the upstream molecule of erk1/2, raf-1. 24967732_3 and the inhibitory effects induced by erk1/2 or jnk could be rescued by bancr overexpression. 19269153_1 transfection with anti-mir-16 inhibitor suppressed mir-16 expression and counteracted the egcg effects on bcl-2 down-regulation and also induction of apoptosis in cells. 24312495_1 we deploy a microrna sponge strategy to inhibit mir-150 in vitro, and the result demonstrates that the 3'-untranslated region of p2x7 receptor contains a highly conserved mir-150-binding motif and its direct interaction with mir-150 down-regulates endogenous p2x7 protein levels. 24312495_2 mir-150 levels correlate inversely with p2x7 in breast carcinomas and breast cancer cell lines. 24312495_3 thus, our data strongly suggested that mir-150 negatively regulates the expression of p2x7 by directly targeting the 3'-utr of p2x7 transcript. 26170952_1 mir-205 directly targets the 3-utr of the chop gene in osteoblasts. 26170952_2 mir-205 negatively regulates chop protein expression through targeting its 3-utr. 23572509_1 mir146b binds to the 3' utr of stat3a and stat3b. 23572509_2 mir146b upregulation during pregnancy and lactation may mediate the maintenance of alveolar luminal progenitor cells by selectively suppressing stat3b and to a lesser extent stat3a. 23572509_3 therefore, we conclude that during pregnancy mir146b is involved in luminal alveolar progenitor cell maintenance, at least partially, by regulating stat3b. 24394555_1 smad7 is a direct functional target of mir-181a. 23902763_1 overexpression of mir-34a mimics decreased notch-1 protein levels, indicating that mir-34a negatively regulated notch-1 expression in nsclc cells . 23902763_2 next, we performed a luciferase reporter assay to confirm the direct regulation of notch-1 by mir-34a with rhamnetin or cirsiliol treatment in the two nsclc cell lines. 23902763_3 our findings demonstrated that mir-34a could directly bind to the 3'utr of notch-1 and suppressed luciferase expression in the presence of rhamnetin or cirsiliol. 23902763_4 these data indicated that notch-1 is a direct target gene of mir-34a in nsclc cells treated with rhamnetin- or cirsiliol-radiation combinations. 23902763_5 taken together, these results suggest that mir-34a-mediated inhibition of notch-1 expression by rhamnetin and cirsiliol reduces emt in nsclc cells. 20980827_4 we also observed a good negative correlation between satb2 protein expression and mir-31 . 20980827_6 these data confirm that satb2 is a direct target of mir-31. in summary, our data indicate that expression of mir-31 in fibroblasts suppresses tumor cell motility and invasion, at least in part, by targeting the satb2 homeobox gene. 25421410_1 we found that transgelin 2 contained two theoretical mir-133a binding sites in its 3'-utr. 25421410_2 co-transfection of mir-133a suppressed the luciferase activity of the reporter containing wild-type tagln2 3'-utr sequence, but failed to inhibit that of mutated tagln2 by dual-luciferase reporter assay. 25421410_4 the expression of tagln2 protein level was suppressed by mir-133a transfection while expression was enhanced by anti-mir-133a. 25421410_5 these results demonstrated that endogenous tagln2 expression is directly targeted and regulated by mir-133a and suggested that mir-133a could exert its anti-apoptotic function via inhibiting tagln2 expression. 25971362_1 forty-eight hours after tf-np treatment, mv4-11 cells receiving antagomir-155 had a 5-fold decrease in mature mir-155 levels compared to cells receiving a scramble control . 25971362_3 in summary, decreased mir-155 expression by mln4924 resulted in re-activation of ship1 tumor suppressor expression and inhibition of active akt. 25971362_4 as expected, 24-hr treatment of scramble mir-transfected cells with 500 nm mln4924 resulted in upregulation of known direct targets of mir-155, ship1 and pu.1 proteins , as well as induction of apoptosis, determined by annexin v staining . in contrast, overexpression of mir-155 partially prevented the induction of ship1 and pu.1 proteins, as well as the impact of mln4924 on apoptosis . 19671135_1 we found that nppa-as is expressed in a number of human tissues as a collection of alternatively spliced isoforms and that nppa-as and nppa can form rna duplexes in vivo. 19671135_2 we also demonstrated that a specific nppa-as isoform is capable of down-regulating the intron-retained nppa mrna variant. 19671135_3 we detected no correlation between the expression of correctly spliced nppa and its antisense transcript , but instead observed a strong positive correlation between the expression levels of nppa-as and nppa variants with retained intron 1 . 19671135_4 this result was confirmed by using an alternative set of primers detecting the same nppa-as isoforms and retained nppa intron 1 . 19671135_5 such correlation further indicates a possible functional relationship between nppa-as expression and posttranscriptional regulation of nppa. 19671135_6 these results indicate that nppa and nppa-as interact at the rna level and that a specific nppa-as isoform can modulate the proportion of intron-retained nppa. 26150338_2 the 3'-utr of lass2 with wild-type and mutant binding sites for mir-9a was cloned into pmir-rb-report vector. 26068950_3 together, our results provide support for a model whereby mir-620 targets hpgd, resulting in accumulation of hpgd-檚 substrate, pge2, and signaling by pge2 through the ep2 receptor results in cancer radiation resistance . 22407812_1 the ba-induced sp1, sp3, and sp4 downregulation was accompanied by increased zinc finger zbtb10 expression, a putative sp-repressor and decreased microrna-27a levels, a microrna involved in the regulation of zbtb10. 25444913_2 mir-145 was found to directly target hmga2 by luciferase assay and western blotting. 25444913_3 our findings suggest that mir-145 functions as a tumor suppressor in ovarian cancer and directly targets hmga2 oncoprotein. 25444913_4 low mir-145 and high hmga2 expressions are potential biomarkers of poor prognosis of ovarian carcinoma and mir-145 is the more powerful predictor of patient outcome. 20841484_2 mutation of the mir-152 target site abrogated the reduction in luciferase activity, leading us to conclude that mir-152 directly target dnmt1, consistent with a report by branconi and colleagues demonstrating mir-152 targeting of dnmt1 in a gallbladder cancer cell line . 26330060_1 these results indicated mir-33a negatively regulates twist1 expression, but not pim-1 in these two tested nsclc cell lines. 26330060_2 in other words, mir-33a expression is specifically and inversely correlated with twist1 expression in nsclc cells. 26330060_3 together, these results indicate that mir-33a mediates emt by regulating its target of twist1. 26330060_4 collectively, these results might explain the regulatory mechanism through which mir-33a represses emt, that most likely involves the inhibition of twist1. 26383522_1 mir-3666 targets 3'-utr of zeb1 mrna to inhibit its translation in cc cells. 26383522_2 mir-3666 targets 3'-utr of zeb1 mrna to inhibit its translation. 22528944_1 bioinformatics and luciferase reporter assays revealed that mir-10b bindhe 3'-utr of cadm1 mrna and represses its translation. 22528944_2 western blot and qrt-pcr showed that cadm1 is inhibited by mir-10b over-expression. 22528944_3 cadm1 is a direct and functional target of mir-10b. 22528944_5 meanwhile, we found that hoxd10 is also regulated by mir-10b in hcc cells, with a corresponding change in the level of rhoc . 22528944_6 these results indicated that the prometastatic effect of mir-10b is partly mediated through regulation of cadm1 expression. 25647305_1 p21 was reported to be one of the target genes of mir-17 and mir-20a . 25647305_2 we found nc could markedly upregulate p21 , whereas overexpression of mir-17 and mir-20a antognized the protein level increment of p21 in k562 cells after treatment with nc . 26915797_1 tgfbi mrna levels were significantly decreased in cells transfected with mir-9 , mir-21 , and mir-181a compared with those in cells transfected with the negative control mirna mimic . 22574173_1 furthermore, we show that mir-96 and mir-182 negatively regulate spast by effects on mrna stability and protein level. 22574173_2 we demonstrate that the transcription factors nrf1 and sox11 as well as the micrornas mir-182 and mir-96 are major factors involved in the regulation of spast. 22574173_3 we conclude that the related mir-96 and mir-182 family of mirnas provide strong regulation of spastin synthesis in human neural cells and affect both mrna and protein levels, and that this mechanism likely extends across all tetrapod organisms. 22574173_4 in this work, we have shown that mir-96 and mir-182 negatively regulate mrna and protein levels of spastin, with the target sites in the spast 3'-utr conserved in all sequenced tetrapod species. 26632693_1 in the inhibitor group, the relative expression of il-1f5 in the inhibitor trans-fection group was significantly higher than that in the control group ; it showed that mir-197 inhibitor could upregulate the expression of il-1f5 in sgc-7901 and bgc-823 cells after mir-197 inhibitor transfected successfully. 20656888_1 the role of fas as a targetgene was substantiated by abrogation of mir-146a, which markedly increased fas protein expression. 20656888_2 importantly, overexpression by precursor mir-146a expression plasmid reduced luciferase activity when cotransfected with the plasmid containing the 3'-utr of the fas gene , indicating that forced expression of mir-146a downregulates fas expression via targeting its 3'-utr . 20656888_3 taken together, these results demonstrated that fas is the major target of dz-induced mir-146a expression for inhibition of apoptosis. 22877943_1 a luciferasereporter assay suggested that mir-133a interacted with hla-g 3' utr. 22877943_2 multi-software prediction and real-time pcr confirmed that mir-133a was most likely to bind to hla-g 3'untranscribed region . 22877943_3 the results from the luciferase reporter assay strongly suggested binding of the hla-g 3'utr by mir-133a. 22877943_4 however, mir-133a significantly decreased hla-g protein expression in jeg-3 cells compared with controls , indicating that hla-g expression is down-regulated by mir-133a at the protein level, not by targeting of hla-g mrna for degradation. 23583196_1 we demonstrate that the brain-enriched microrna, mirna-125 is a bona fide negative regulator of smg1 in humans. 23583196_2 down-regulation of smg1 expression is mediated by mirna-125 binding to a microrna response element in the 3' untranslated region of smg1 mrna, which leads to degradation of the smg1 mrna. 23583196_4 these data indicate that the predicted binding sites in the seed sequence are critical for the direct and specific binding of mir-125 to the smg1 mrna. 23583196_5 our results suggest that mir-125a and mir-125b decreased smg1 levels by degradation of the targetsmg1 mrna. 20643754_1 upregulation of the mir-29 family resulted in decreased levels of its targets dnmt3a and mcl1, consequently affecting dna methylation and apoptosis. 22613005_1 we searched the list of downregulated genes implicated in the regulation of angiogenesis by ectopic expression of mir-214 in sk-hep1 and mahlavu cells as well as searched the candidate target genes of mir-214 predicted by software analysis .using 22613005_3 identified the potential target sequences at the 30-utr of hdgf mrna, cloned the 30-utr, and constructed a corresponding mutant as control for a luciferase reporter assay .downregulation of endogenous hdgf expression by ectopic expression of mir-214 in sk-hep1 cells was further confirmed at the protein level by immunoblotting assays . 26064232_1 mir-298 was predicted as a regulator of bax and further study verified bax was a target gene of mir-298 by luciferase reporter assay. 26064232_2 bax is involved in bufalin induced gastric cancer cell apoptosis and is predicted as a potential target gene of mir-298. 26064232_3 bioinformatic analysis showed that bax was directly suppressed by mir-298. 26064232_5 compared with control, endogenous bax mrna levels were down-regulated when mgc803 and sgc7901 cells were transfected with mir-298. 26064232_6 bax protein was down-regulated in the mgc803 and sgc7901 cells with mir-298. 26064232_8 site-directed mutagenesis of the mir-298 binding site in bax 3'-utr was performed using genetailor site-directed mutagenesis system and named mutant 3'-utr. 18381893_1 mir-200 was found to directly targetthe mrna of the e-cadherin transcriptional repressors zeb1 and zeb2 . 18381893_2 a strong inverse correlation between the expression of mir-200 and zeb1 and zeb2 mrna was detected. 18381893_3 the correlation between mir-200 and zeb2 mrna was especially striking, with not a single cell line expressing both mir-200 and zeb2 . 18381893_4 taken together, these data strongly suggest that in the 59 cancer cell lines, both zeb1 and zeb2 mrna are targeted by endogenous mir-200. 18381893_5 collectively, the data demonstrate that the mir-200 family is a powerful regulator of emt/met by targeting zeb1 and zeb2, which control the expression of e-cadherin. 21426775_1 mirna-21 expression was decreased in mirna-21 antisense oligonucleotide group. 21426775_3 ki67, bcl-2, mmp-2 and mmp-9 protein were down regulated while pten and timp-1 protein expression was increased. 25653162_1 to further validate participation of snr40 in methylation of gm562, we constructed a quadruple mutant, where we deleted all four snornas involved in gm methylation of 18s rrna: snr40, snr41, snr56 and snr57, and analyzed the 18s rrna from this quadruple mutant. 25653162_2 as seen in figure 3g deletion of all four snorna led to complete loss of gm residues from the 18s rrna, which further augments the importance of snr40 in gm562 methylation. 25653162_3 this clearly showed that snr40 is involved in methylation of gm at potion 562 in the helix 18 of 5' central domain of 18s rrna. 24876306_1 using qpcr and dual luciferase technology we show that mir-155 delivery resulted in a significant increase in cellular mir-155 which facilitated a downregulation of socs1 gene expression and a functional increase in il-6 and ifn-beta cytokines. 26807196_1 furthermore, srcin1 was confirmed asthe direct target of mir-873 by luciferase reporter assay and western blotting. 26807196_2 overexpression of mir-873 promoted the proliferation and migration of lung adenocarcinoma cells, while srcin1 upregulation inhibited their proliferation and migration. 26807196_3 restoration of srcin1 could significantly reverse the proliferation and migration promotion imposed by mir-873. in summary, this study reveals for the first time that mir-873 increase the lung adenocarcinoma cell proliferation and migration through directly inhibiting srcin1 expression. 25867271_1 we found that mir-367 downregulated smad7 expression by directly targeting its 3'-utr in human pancreatic cancer cells. 25867271_2 we found that mir-367 overexpression significantly suppressed expression of smad7 at both mrna and protein levels . 25867271_3 we found that mir-21 and mir-106a mimics also inhibited luciferase activity and suppressed the expression of smad7 at mrna and protein levels in panc1 cells . in addition, the levels of mir-21 and mir-106a negatively correlated with smad7 mrna level in pdac patients . 25867271_4 these results were obtained from both hek293 cells and the pancreatic cancer cell line panc-1 , suggesting that mir-367 suppresses smad7 expression through directly targeting the mirna-binding site in the smad7 3'-utr. in addition, mir-367 expression in the cancer tissues with negative smad7 expression was significantly higher than those with positive smad7 expression, suggesting a negative correlation between mir-367 and smad7 expressions . 25867271_5 therefore, these results suggest that smad7 mediated the invasion-promotion function of mir-367 in pancreatic cancer cells, and smad7 was a functional target of mir-367. 22357618_2 cotransfection of pegp-mir-212 with wild-type ptch1 3'-utr and control renilla luciferase reporter construct prl-tk revealed a 90% fold decrease of firefly luciferase activity compared with that of the mutant ptch1 3'-utr, indicating that mir-212 can modulate ptch1 gene expression via the mir-212 binding sites in its 3'-utr . 22357618_3 the result indicated mir-212 could decrease ptch1 expression by mrna cleavage. 22357618_4 the results seen with transient transfection and bulk selected cells indicated ptch1 may be the effector that mediates the functional role of mir-212 on cell proliferation. 22074923_1 ectopic expression of mir-34c reduced the self-renewal of bt-ics, inhibited epithelial-mesenchymal transition, and suppressed migration of the tumor cells via silencing targetgene notch4. 22074923_3 2b, the mir-34c mimics significantly reduced the luciferase activity of the reporter with notch4 gene 3'-utr. 22074923_4 these results suggest that mir-34c suppresses the self-renewal capacity of bt-ics and thus reduces the number of bt-ics via targeting notch4. 21945314_1 mir-143 down regulates ptn expression through interaction with a target site of mir-143 in the coding region of mouseptn. 21945314_2 by contrast, mir-143 inhibitor slightly enhanced ptn expression in both mrna and protein level. 21945314_3 these results indicate that mir-143 may directly target the coding region of ptn. 21945314_4 these results further demonstrate that a cluster of rare codons upstream of mir-143 target site is required for mir-143-induced translational knockdown of ptn when the binding site is located in the coding region. 21128942_1 the lncrna emx2os is generated from the opposite strand of the homeodomain transcription factor emx2 gene in neuronal precursor cells . 21128942_2 emx2os post-transcriptionally regulates the abundance of the coding transcript, thereby regulating activity of emx2 . 22276989_1 wnt1 is a direct target of mir-122 endogenously. 22276989_2 mir-122 down-regulated the expression of wnt1 protein. 22573493_1 we identified col4a1 mrna as a mir-21 targetin the gc lines. 22573493_2 these primers were designed to introduce apai restriction sites within pcr products, which generate mutation within the putative mir-21 recognition site of human col4a1 3'-utr. 22573493_3 taken together, these results demonstrate that col4a1 is a target of mir-21 in kgn cells. 22573493_4 furthermore, we experimentally identified col4a1 as a mir-21 targetby cdna cloning of eif2c2-bound mrnas and subsequent validation. 22573493_5 figure 5. col4a1 silencing by mir-21. 22573493_6 a, targetvalidation of mir-21 using a luciferase assay of kgn cells transfected with pre-mir-21 or nc at 20 nmol/l. 22573493_7 luciferase activities normalized for renilla luciferase activities in pmir-col4a1-, pmir-col4a1mut-, and pmir-reporttransfected cells are shown. 26796260_1 taken together, these results provided compelling evidence that mir-670-5p directly binds to the 3'utr of prox1 and prox1 was one target of mir-670-5p 26365191_1 a luciferase assay demonstrated that all four mirnas target erbb4, and sirna knockdown of erbb4 partially recapitulated the effects of mir-combo. 26365191_2 we found that each individual mirna can signi铿乧antly reduce luciferase activity, suggesting that each mirna in the mir-combo can target erbb4 . 26365191_4 in terms of the mechanism underlying mir-combo-driven maturation, we found that all four of these mirnas can independently repress erbb4 and that expression of these four mirnas increases during cardiac development . 26335100_1 since, mir-125b is known to target p53 mrna and, by doing so, to down-regulate its expression, we hypothesized that down-regulation of mir-125b by ct-cx43 may influence the expression of p53. 21984125_1 we show a direct repression of vil6 by hsa-mir-1293 and hil6 by hsa-mir-608. 21984125_2 the repression of vil6 by mir-1293 was reversed by disruption of the vil6 mir-1293 seed match through the introduction of point mutations. 16766263_1 mir-127, is embedded in a cpg island and is highly induced from its own promoter after treatment. 23059786_1 more intriguingly, mir-17 and mir-20a directly inhibit the p21 and stat3 expression, both of which can reverse mir-17/mir-20a-mediated abrogation of hif-1a-induced differentiation. 23059786_2 we further show that these two mirnas target p21 and stat3 . 23059786_3 all these data support the conclusion that mir-17 or mir-20a may suppress both p21 and stat3 protein expression through directly targeting their 3' utr at the post-transcriptional level. 23059786_4 here, we show that mir-17 and mir-20a can target the p21 and stat3 3' utr to inhibit the expression of p21 and stat3 in human cells. 23238785_2 we found that estrogen down-regulates mir-21 biogenesis so that fasl, the targets of mir-21, protein levels are posttranscriptionally increased that induce osteoclastic apoptosis. 21798241_1 we found that mirna-22 and mirna-140-3p significantly suppressed nf-kappab activity by regulating the expression of nuclear receptor coactivator 1 and nuclear receptor-interacting protein 1 , both of which are nf-kappab coactivators. 21798241_2 these results suggest that mir-22 enhances nf-kappab activity by modulating the expression of the nf-kappab coactivator ncoa1. 21798241_3 fig.2.mir-22 target the nf-kappab coactivator ncoa1. 21798241_4 we then tested whether mir-140 directly target nrip1 by generating a luciferase reporter carrying the region of the nrip1 3'-utr that itself contains the first putative mir-140-3p targetsite . in addition, huh7 cells infected with mir-140 precursor-overexpressing lentiviruses showed decreased expression of nrip1 . 21798241_5 these results indicate that nrip1 is normally targeted by mir-140-3p. 21798241_7 3.mir-140-3p target the nf-kappab coactivator nrip1. 24993091_1 we analyzed the effects of mir-449a overexpression on cdc25 expression, proliferation, invasion and apoptosis of hec-1b cells. 24993091_2 we found that mir-449a and mir-449b levels were markedly reduced in type ii endometrial cancer tissues but not in type i endometrial cancer tissues compared with normal endometrium. 24993091_4 mir-449a overexpression also induced apoptosis in hec-1b cells. in addition, real-time rt-pcr and western blot analysis showed that cdc25a expression was suppressed by mir-449a overexpression. 24993091_5 our results suggest that mir-449a may act as a tumor suppressor by targeting cdc25a in endometrial cancer. 26268439_1 figure 6 efnb2 and vegfa are mir-503 target genes. 26268439_2 moreover, transfer of endothelial mps carrying mir-503 into pericytes reduced the expression of efnb2 and vegfa, whereas use of rock or nf-kappab inhibitors has prevented the downregulation of the two mir-503 target genes . 26268439_3 furthermore, using a coculture system described above, we have demonstrated that treatment with eptifibatide prevented the transfer of mir-503 through mps from ecs into pericytes , preventing the downregulation of target genes, vegfa and efnb2 by mir-503 . 25764126_2 mirna-128 was able to bind with the 3'-untranslated regions of bmi-1, bag-2, bax, h3f3b, and paip2 mrnas, resulting in significant reduction of the targeted protein levels. 26036258_1 the direct regulation of sirt1 expression by mir-132 was demonstrated using luciferase assays. 26036258_2 collectively, the data obtained from the gep analysis, in vitro transfection assay and ex-vivo correlative studies demonstrate a direct link between mir-132 and sirt1 expression in cll. a direct functional link between mir-132 and sirt1 in cll was demonstrated by taking advantage of the cll-like models mec1 and eheb, in which an ad-hoc luciferase assay and the transfection of microrna precursor of mir-132 clearly showed the capability of mir-132 to directly down-regulate sirt1 expression, as also found in other cell systems . 26299712_1 we confirmed that mir-92a regulates klf2 expression by binding to sequences in its 3'-utr. 26631964_1 as reported in the targetscan database, sert is a potential target of mir-24 . 26631964_2 the relationship between mir-24 and sert was confirmed using luciferase reporter assay in human intestinal epithelial cells. 26631964_3 mir-24 mimic decreased 3'-utr activity of sert and the expression of sert in mrna and protein levels, while the mir-24 inhibitor increased these levels. 26631964_4 the effect of mir-24 on sert expression regulation in ibs mice was also investigated after the administration of mir-24 inhibitor. 26631964_5 as shown in fig 4d, mir-24 inhibitor reversed the tnbs induced decrease of sert protein expression. 22588173_1 this result indicates that mir-140 directly bind to the spp1 transcript and post-transcriptionally regulate spp1 gene expression. 24647998_1 mir-1303 could bind to the putative binding sites in cldn18 mrna 3'-utr and visibly lower the expression of claudin-18. 21816823_1 finally, er stress activates creb through tox3 while creb is a target gene of mir-34a and involved in neurites growth and synaptic plasticity. 21816823_2 these results placed mir-34a as a major player involved in neuronal deregulation induced by vpr. 22811431_1 in addition to mir-34a, mir-199a has also been associated with sirt1 regulation. 22811431_2 knockdown of mir-199a results in the upregulation of sirt1 and hif1alpha . 22811431_3 as this report found that mir-199a levels were decreased in cardiac myocytes upon hypoxia, the data indicate that sirt1 is important for hypoxic damage 22634383_1 the microrna mir-23 target gls mrna and inhibits expression of gls protein. 22634383_4 however, we still observed a reduction of gls mrna in these cells, suggesting that mir-23 target gls in several cellular contexts. 26189797_1 mir-21 inhibits the translation of pdcd4 mrna in mcf7 breast carcinoma cells by binding to a target site within the 3'-utr9 . 26189797_2 this suggested that high level of mir-21, and low level of hur, resulted in translation repression of pdcd4 in huh7 cells even in the presence of high level of pdcd4 mrna. 23453925_1 in both in vivo sensor assay and in vitro luciferase assay, mir-932 can suppress boi by directly binding to its 3 ' utr. 23453925_2 these data indicate that mir-932 can suppress boi protein level in vivo. 23453925_3 together, these findings suggest that mir-932 modulates the hh signaling by directly targeting boi 3 ' utr. 26683818_1 moreover, lasp-1 was proved to be a direct target gene for mir-203. in conclusion,our results demonstrated that mir-203 downregulated lasp-1 expression by directly targeting the 3'-utr of lasp-1 mrna. 26683818_2 based on computational predictions and experimentalvalidation,we identified lasp-1 as a novel target for mir-203 in nsclc. 22354898_1 these results indicate that mir-144/451 can rapidly turn off rac-1 protein production due to their small size, non-coding nature and directly acting on the ribosome. 26780942_1 hmg-慴ox transcription factor 1 was identified as a novel target of mir- 155, which mediated its effect on crc via the wnt/ -beta -慶atenin pathway. 26780942_2 during the identification of possible targets of mir- 155, hbp1 was identified as a gene, which contains a putative mir- 155 mre within its 3'-慤tr. 26780942_3 in conclusion, the present study demonstrated that mir- 155 promoted the growth of crc in vitro and in vivo, and hbp1 was verified as a target gene of mir- 155. 18056638_2 to prove that the nfi-a mrna is a mir-424 target, the 3- utr of nfi-a was inserted downstream of a luciferase orf . 18056638_8 altogether, these data demonstrated that nfi-a is a target of mir-424. 18056638_9 these results show that nfi-a down-regulation is important for monocytic differentiation, therefore indicating that one of the pathway by which mir-424 promotes monocytopoiesis is through nfi-a repression. 21827757_1 we found that mir-451 negatively regulated the expression of ywhaz through ywhaz 3'utr and that ywhaz was required for the mir-451-mediated downregulation of p38 mapk signalling. 21827757_2 these data indicate that mir-451 can negatively regulate ywhaz expression. 21827757_4 1.mir-451 regulates ywhaz expression via the ywhaz 3'-utr. 21827757_5 our combined results provide a strong support that 3'-utr of ywhaz is indeed a target of mir-451 and mir-451 negatively regulates the expression of ywhaz through the ywhaz 3'-utr. 21827757_6 therefore, it is tempting to speculate that over-expression of mir-451 might have an effect on some dn related genes via down-regulation of ywhaz. in conclusion, mir-451 prevented mesangial hypertrophy by targeting the reduction of ywhaz and p38 mapk signaling in vivo and in vitro. 26600038_1 further, luciferase reporter assays and seed-sequence mutagenesis confirmed that mir-17 and -20a bind to nor-1 3'-utr. 26600038_2 herein, we demonstrate that two members of the mir-17-92 cluster bind to the human nor-1 mrna thereby modulating the endothelial expression of genes dependent on this transcription factor. 26600038_3 therefore, taken together these data suggest that the early-gene nor-1 could be a bona fide target gene of the mir-17 family after stimuli that transiently increase its expression. 26600038_4 these findings confirm that members of the mir-17 family bind the nor-1 3'-utr region. 26600038_5 cross-species conservation of a potential binding site often underscores a genuine target gene, thus, in silico analysis strongly suggest nor-1 as a novel target for mir-17 family. 26279439_1 the dual luciferase reporter assay and western blot demonstrated that pten was the target gene of mir-499-5p. 26279439_2 these data suggest that pten is the target gene of mir-499-5p. 18614545_3 pooled analysis resulted in a highly significant association of c.*76g>a with female ibs-d . in a reporter assay, c.*76g>a affected binding of mir-510 to the htr3e 3'utr and caused elevated luciferase expression. 18614545_4 htr3e and mir-510 co-localize in enterocytes of the gut epithelium as shown by in situ hybridization and rt-pcr. 26309359_1 luciferase reporter assays and western blot analysis confirmed the eif5a2 gene as a target of mir-30b. 26309359_2 these results indicate that the 3'-utr of eif5a2 was targeted by mir-30b. 26309359_3 these results suggest that mir-30b enhances e-cadherin and -beta-catenin expression by targeting eif5a2 and eventually inhibits the emt process in gastric cancer cells. 26455323_1 these results show a preferential regulation of zeb1 rna by mir-200 and an additional effect of mir-150, and support that the repression of claudin-7 by spry2 is mediated by zeb1. 26513648_1 mir-17 inhibi ts mcl-1 expressionby interacting with its 3'-utr. 26513648_2 hek293 cells were co-transfectedwith plasmids expressing mcl-1 3'-utr and -beta-galactosidase, along with mir-17mimic . 26513648_3 suggesting that mir-17 overex-pression interferes with the ability of mcl-1 to sequesterbeclin-1, thereby facilitating autophagy. 22384141_3 notably, mir-126 also directly target the kras transcript at a "seedless" binding site within its 3'utr. in clinical specimens, mir-126 was strongly down-regulated in pdac tissues. 22384141_4 his indicates that mir-126 directly regulates kras at post-transcriptional levels through a 'seedless' interaction with its 3'-utr. 22384141_5 we show a down-regulation of mir-126 in pdac, with increased expression of kras. 22384141_6 as a result, we evaluated a possible role for mir-126 in regulating kras and found that it is able to directly regulate kras, inhibiting its protein translation by interacting with a -渟eedless- site within its 3'-utr. 26593208_1 second, mir-9 decreased foxo1 expression by directly inhibition of its mrna translation. 26593208_2 these results suggest that mir-9 negatively regulated foxo1 translation through directly binding to its 3'-utr. 26593208_3 these results suggest that foxo1 is a downstream target of mir-9 in nsclcs. in addition, we detected the effect of foxo1 on erlotinib induced growth inhibition. 26593208_5 these results suggest that mir-9 regulated foxo1 expression is a target of erlotinib in nsclcs. 22696253_1 further study revealed that mir-124 targeted the 3'utr of stat3 gene so as to suppress the expression of stat3 protein but did not affect its mrna level. in summary, we found that mir-124 regulated myogenic differentiation of bmscs via targeting stat3 mrna, luciferase assay in hek293 cells for the post-transcriptional repression of stat3 by mir-124. 22696253_2 the phosphorylation of stat3 protein in cocultured bmscs was obviously inhibited after mir-124 transfection but upregulated after amo-124 transfection. 22696253_3 these indicate the regulation of cardiomyocyte differentiation of bmscs by mir-124 via targeting stat3. 23071643_1 hpasmcs that over expressed mir-206 were found to have lower notch3 protein levels as compared to controls, while those transfected with antimir-206 had increased expression levels of this protein . 23071643_2 these results indicate that mir-206 inhibits notch3 expression in hpasmcs. 23071643_3 this data suggests that, mir-206 rescues notch3 mediated proliferative effects in hpasmcs. 22102884_1 our data indicate that bart9 is involved in nktcl proliferation, and one of its mechanisms of action appears to be regulating lmp-1 levels. 20308325_1 expression of sox9, which is a recently validated target of mir-124 , was also increased in response to reverse signaling , suggesting that modulation of mir-124 levels by reverse signaling might have a ripple effect on multiple mir-124 target. 25492481_4 the luciferase activity suggested that igf1r and bcl2 were both target genes of mir-143. 23778472_1 simultaneously expressed mir-424 and mir-381 synergistically suppress the proliferation and survival of renal cancer cells---cdc2 activity is up-regulated by targeting wee1.we 26298722_1 we used targetscan database and found that bnip3 was the putative target of mir-944 . 26298722_3 therefore, we inferred that the downregulation of bnip3 which is the proapoptotic gene is the target of mir-944 and essential for the cisplatin resistance. 26298722_4 the bnip3 level was reduced significantly in mir-944 group compared with nco group, and the expression of bnip3 was upregulated in mir-944 inhibitor group because the mir-944 was knockdown in mcf-7/r cells.we 26298722_5 indicated that the expression of bnip3 was negatively regulated by mir-944, which may play an essential role for the chemoresistance in cispaltin-resistant breast cancer cells. 26431046_1 furthermore, we identified hes1 as a direct target of mir- 381 in neural stem cells. 26431046_2 furthermore, we identified hairy and enhancer of split 1 as a direct target of mir- 381 in neural stem cells. 26431046_3 mir- 381 promoted neural stem cells proliferation and differentiation to neurons by targeting hes1. 25096247_1 we studied the effects of mir-194 in osteosarcoma and the possible mechanism by which mir-194 affected the survival, apoptosis and metastasis of osteosarcoma. 25096247_5 luciferase reporter assay, real-time quantitative pcr and western blotting confirmed that cdh2 and igf1r were targets of mir-194. 25096247_6 using real-time quantitative pcr, we evaluated the expression of mir-194 and two mir-194 target genes, cdh2 and igf1r in osteosarcoma samples from 107 patients and 99 formalin- or paraformalin-fixed paraffin-embedded tissues. 25096247_7 the expressions of the target genes were also examined in osteosarcoma samples using immunohistochemistry. overexpression of mir-194 inhibited tumor growth and metastasis of osteosarcoma probably by downregulating cdh2 and igf1r. 25096247_8 mir-194 may prove to be a promising therapeutic agent for osteosarcoma. 21427358_1 taken together, these results demonstrated that mir-95 increases proliferation by directly targeting snx1, defining mir-95 as a new oncogenic mirna in crc. 21427358_2 figure 3. mir-95 suppresses snx1 expression by directly targeting its 3'utr. in concordance with these results, endogenous snx1 protein levels were also down-regulated in mir-95-overexpressed cells and could be restored in mir-95 depleted cells . 21427358_3 the snx1 mrna levels were not decreased in mir-95 stable cell lines when compared with cells transfected with an empty vector . 21427358_4 taken together, these results proved that mir-95 promotes crc cell proliferation via directly targeting snx1. 26731713_1 taken together, these data demonstrate that mir- 194 negatively regulates yap1 expression by directly binding to yap1 3'-utr sequence. 22358059_1 reporter analysis showed direct binding of mir-196a to the 3' untranslated region of col1a1 and col3a1. 22358059_2 therefore, type i and iii collagens are strong candidates that are regulated by mir-196a. 22358059_3 these results suggest that mir-196a regulates the secretion of collagens i and iii in fibroblasts of dermal tissue. 22358059_4 these findings suggest that mir-196a directly regulates the expression of collagens i and iii through targeting the 3'-utrs of the col1a1 and col3a1 genes in fibroblasts. 21628465_1 we have found that the putative mir-107 targetcyclin-dependent kinase 6 expression is increased by tlr4 as a result of the decrease in mir-107. 21628465_2 to confirm that mir-107 is directly targeting the 3'-utr of cdk6, a luciferase construct containing the 3'-utr of cdk6 with the wild-type mir-107 seed sequence located at position 308-314 or a mutated form at a single nucleotide was used. 21628465_3 transfection with anti-mir-107 resulted in enhanced tnf-alpha secretion compared with cells transfected with anti-mir-control. 21628465_4 overall, therefore, our results indicate that a decrease in mir-107 induced by lps leads to an increase in cdk6 expression, which in turn leads to macrophage adhesion with cdk6 also having a role in lps lethality in vivo. 21628465_5 apart from cdk6, we also found two other potential mir-107 target to be up-regulated by lps: hif-1alpha and dicer1. 21628465_6 we also examined dicer1 and hif-1alpha, two other identified targetgenes of mir-107 to determine whether their mrna also increased in response to lps . 25340781_2 together, these results indicated that mapk6 was a target of mir499a. in our research, we firstly demonstrated mapk6 was a direct target gene of mir499a 26111969_1 pten is identified as a target gene of mir-19a. 23469855_2 we identified the 3'-utr of bcl-2 as the target for mir-15b. 23469855_3 taken together, these results suggest that 1 ischemia-induced mir-15b actively suppresses protein translation by targeting the 3'-utr of bcl-2, and 2 functional suppression of mir-15b is required for bcl-2 expression following sevoflurane preconditioning. 23469855_4 taken together with the novel findings that 1 the neuroprotective paradigm of sevoflurane preconditioning robustly suppresses mir-15b expression following ischemia, 2 targeted inhibition of mir-15b can mimic the protective effects of sevoflurane preconditioning, and 3 bcl-2 mrna is effectively targeted by mir-15b via its 3'-utr under neural ischemic conditions, we propose the targeting of mir-15b expression as a novel neuroprotective strategy against ischemic injury. 23013135_1 zeb1 was directly suppressed by mir-150 in escc. 23013135_2 mir-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the emt inducer zeb1. in vitro assays showed that emt-inducer-zeb1 is a new direct target of mir-150. 23013135_3 analysis of the regulation of zeb1 by mir-150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in escc. 23013135_4 these data suggested that zeb1 mrna was a direct functional target of mir-150. 22613985_1 moreover, experimental data supported bioinformatic predictions that mir-106b served as an anti-apoptotic modulator through inhibition of p21 expression and mir-15b displayed anti-angiogenesis activity. 23226395_1 takentogether it is demonstrated that mirna-449a plays an important role in modulating expression of ykl40 through targeting the components of the notch signaling pathway following hcv infection. 26913609_1 we showed that mir-27a modulates a group of proteins involved in mhc class i cell surface exposure and, mechanistically, demonstrated that calreticulin is a mir-27a direct target responsible for most downstream effects in epistasis experiments. 26913609_2 calreticulin, thus, is a direct target of mir-27a and mediates the effects on mhc class i exposure. 26283635_1 we subcloned the 3'-utr or the ones with mutated mir-binding sites into a mir reporter plasmid to study the role of mir-23a/b, mir-200, mir-186 and mir-381 in cx43 gene expression . 26283635_2 as expected, mir-23a, mir-23b and mir-200a dramatically suppressed cx43 expression activity . 26283635_3 however, mutation of the potential element for mir-23a or mir-23b could not rescue the inhibitory role of mir-23a or mir-23b in cx43 expression , indicating that mir-23a/b did not suppress cx43 expression in a direct manner via the predicted binding sites. 26283635_4 among the investigated mirs, we identified mir-200a as a novel and direct suppressor of cx43 gene. 26283635_5 mir-200a suppressed human cx43 gene expression via directly targeting at a binding site locating at 909 in the 3'-utr of human cx43 gene. 24462979_3 real-time quantitative pcr revealed a significantly increased expression of mir-193, mir-221 and mir-222, which regulate c-kit, in the 2.0 mg/kg and 8.0 mg/kg treatment groups. 23453369_1 from these data, we concluded that igf-1r might be a direct targetgene of mir-497 in cervical cancer cells. 23453369_2 from these results, we concluded that shrna targeting igf-1r could mimic the effects of mir-497 mimics on malignant phenotypes of cervical cancer cells. 23453369_3 the predicted binding of mir-497 with igf-1r 3'-utr was shown , suggesting that mir-497 might be a potential mirna-targeting igf-1r. 23453369_4 fig 5. mir-497 directly target igf-1r in cervical cancer cells. 23453369_5 sequence of mir-497 binding sites in the igf-1r 3' utr predicted by targetcan and mirbase target, and the 3'-utr region of igf-1r mrna is partially complementary to mir-497. 26892887_1 in addition, we identified a possible target of mir-5100, podocalyxin-like 1 , and demonstrated mir-5100 directly binds to the 3' untranslated region of podxl and post-transcriptionally regulates its expression in pancreatic cancer cells. 26892887_2 these results indicate that mir-5100 directly binds to the 3'utr of podxl and post-transcriptionally regulates podxl expression in ms and sw1990 cells. 26311052_2 malat1 interacts with mir-145 and reduces its expression. 26311052_3 these results suggest that malat1 is a bona fide mir-145-targeting lncrna. 25499621_2 surface expression of pd-l1 induced by chemotherapeutic agents could also be reversed by mir-34a; furthermore, pd-l1 specific t cell apoptosis was reduced as well following mir-34a transfection. 26711782_1 using the publicly available databases targetscan, we found a conserved mir-130b binding site in the 3'-utr of cyld . 26711782_3 the relative luciferase activity was significantly lower in cells after 48-h co-transfection with mir-130b-modified plasmids and p3'-utr-cyld or mir-130b. 26711782_4 mir-130b negatively regulates endogenous cyld expression at posttranslational level. 20479936_1 we identified an evolutionarily conserved binding site for microrna-29b in the 3' untranslated region of the human pgrn mrna. 23015294_1 overexpression of mir883b-5p in preadipocytes down-regulated tbk1 and lbp gene expression by 20 and 40%, respectively . 23015294_2 as expected, blockade of mir883b-5p induced an opposite effect to the mimic and up-regulated lbp mrna levels in preadipocytes . 23015294_3 the blockade of mir883b-5p also induced a 50% rise of lbp mrna in mature adipocytes . 26446137_1 sirt1 is a direct target of posttranscriptional repression by mir-34a. 26446137_2 notably, the inhibition of mir-34a in mscs was concurrent with the increased expression of sirt1 . 26446137_4 these data suggest that sirt1 is likely to be targeted by mir-34a posttranscriptionally. 22156201_1 here, we report in human glioma cell lines that microrna-30e* directly targets the ikappabalpha 3'-utr and suppresses ikappabalpha expression. 22156201_2 together with the lack of alteration in expression of phosphorylated ikks and ikk activity upon mir-30e* overexpression of downregulation ,these results indicate that mir-30e* may directly modulate ikappabalpha expression at the translational level. 22156201_3 point mutations in the tentative mir-30e* binding seed region in the ikappabalpha 3'-utr abrogated the aforementioned repressive effect of mir-30e*, demonstrating that ikappabalpha is a bona fide target of mir-30e* . 22156201_4 figure 4 mir-30e* directly targets the 3'-utr of ikappabalpha. 22156201_5 it is particularly worth noting that retrovirally reintroducing ikappabalpha cdna into two mir-30e/30e* overexpressing glioma cell lines substantially reverse tumor invasiveness ,strongly supporting ikappabalpha as a key mediator for mir-30e*-induced invasion. 22156201_6 taken together, our results suggest that mir-30e* exerts proangiogenic effects through suppression of ikappabalpha expression, which in turn activates nf-kappab signaling. 26872428_1 in addition, luciferase gene reporter assays confirmed that traf5 was a direct target gene of mir-26b and the anti-tumor effect of mir-26b in melanoma cells was significantly counteracted by treatment with traf5 overexpression. 26872428_2 taken together, these results indicated that mir-26b directly targets traf5 via its 3 ' utr in melanoma cells. 26872428_3 we further show that mir-26b inhibits melanoma growth by suppressing the expression of traf5, a direct target of mir-26b, which leads to dephosphorylation of mek1/2 and erk1/2 and the inhibition of antiapoptosis. 18312576_1 the gcvb gene encodes two small, nontranslated rnas that regulate oppa and dppa, periplasmic binding proteins for the oligopeptide and dipeptide transport systems. 26219418_1 we first examined if hoxa5 mrna is a direct target of mir-26a-2 as predicted in our previous study1. 26219418_2 dual luciferase reporter assay results confirmed that mir-26a-2 could bind to the putative binding site in the hoxa5 3'-utr and achieved a 60% knockdown of the luciferase activity . 26219418_4 overexpression of mir-26a-2 significantly decreased the expression of hoxa5 in most of the lps cell lines. 24806323_1 both mir-96 and mir-330 regulate aquaporin5 by binding its utr. 24806323_2 taken together, these findings indicate that aqp5 is a direct downstream target for both mir-96 and mir-330. 23601049_1 then, we identified brain-derived neurotrophic factor as a direct target of mir124a. 23601049_2 these findings suggested that mir124a is a critical regulator for bdnf in rat dls. 20083669_1 these data show that mir-126 is differentially regulated in cf versus non-cf airway epithelial cells and that tom1 is a mir-126 targetthat may have animportant role in regulating innate immune responses in the cf lung. 20083669_2 hek293 cells, which exhibit low levels of mir-126 expression, were used for transient transfections with pmir-tom1-3'-utr. 20083669_3 cotransfection with pre-mir-126 resulted in a significant decrease in luciferase gene expression from the reporter vector containing the tom1 3'-utr when compared with a scrambled control demonstrating direct targeting by mir-126 . 26224477_1 there is one putative binding sites of mir-375 broadly conserved in klf4 3'-utr and cloned the 3'-utr of klf4 mrna and its mutants into downstream of pgl3-control luciferase reporter gene vector ,respectively. 26224477_4 these results indicate that mir-375 directly regulates klf4 in crcs. 25760058_1 in the present study, we found that mir-326 inhibited cell proliferation, migration and invasion, and induced cell apoptosis and cell cycle arrest of crc cells by directly targeting nob1. 26224446_1 in addition, significant negative correlation between fer1l4 and mir-106a-5p expression levels was observed. 26224446_2 among the colon cancer cell lines, fer1l4 levels were relatively lower, with concurrent high levels of mir-106a-5p. 26224446_3 notably, the patient group with both low fer1l4 and high mir-106a-5p expression exhibited a significant difference in prognosis compared with the patient group with high fer1l4 and low mir-106a-5p expression . 17627278_1 we identified mir-221 as a suppressor of endogenous p27kip1 expression. 17627278_3 we have identified and verified mir-221&222 as potent suppressors of p27kip1 expression. 17627278_4 as the expression of gfp in the control-sen-transduced cells remained unchanged, we concluded that mir-221 is a potential regulator of the 3'-utr of p27. 17627278_5 importantly, mutating the seed sequence of mir-221 and mir-222 completely abolished their suppressive activity, indicating that the expression of the mirnas is responsible for p27 suppression. 26722295_1 transforming growth factor--beta-induced factor homeobox 2 , a transcription factor repressing transforming growth factor--beta signaling, was observed to be upregulated and was identified as a target gene of mir-34c. 26722295_2 figure 1. mir-34c expression was downregulated in hbv-associated hcc, and tgif2 is a putative target of mir-34c. 21167132_2 mir-181a decreased k-ras protein level as well as the luciferase activity of reporter vectors containing the 3'-untranslated region of k-ras gene. 21167132_4 these data suggest that mir-181a regulates the 3'-utr of k-ras and inhibits k-ras translation. 26631969_1 notably, mir-409-3p induced downregulation of akt1 protein through binding to its 3 ' untranslated region . 26631969_2 taken together, these results suggest that mir-409-3p downregulates akt1 expression by targeting a specific site in its 3 ' utr. 26631969_3 several lines of evidence in our study indicate that akt1 is a direct target gene of mir-409-3p. 26817521_1 thus, these results showed that mir- 143 directly bound to the 3'-utr region of pai- 1 mrna and suppressed pai- 1 expression in 143b cells. 26817521_2 we identified plasminogen activator inhibitor- 1 as a direct target gene of mir- 143. in this report, we showed that pai- 1 is a direct target gene of mir- 143 and regulates invasion in osteosarcoma. 25150313_1 combined application with chemotherapeutic drugs, mir-200c, a ho-1 inhibitor, may enhance the efficiency of therapy by promoting both apoptosis and autophagy. 19671867_1 the analysis of hcc tissues revealed an inverse correlation between mir-221 and bmf expression and a direct correlation between bmf and activated caspase-3, as a marker of apoptosis. 26864640_1 our work demonstrates that mir- 21 can confer drug resistance to 5- fu in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of mir- 21, pten and pdcd4 can rescue 5- fu sensitivity and the phenotypic characteristics disrupted by mir- 21. further investigation indicated that the essential role of mir- 21 in 5- fu resistance was dependent on its two targets, pten and pdcd4. 26864640_2 these data confirm the regulatory role of mir- 21 on 5- fu resistance through the targeting of pten. 26864640_3 as the first study to show that mir- 21 promotes resistance to 5- fu in pancreatic cancer cells by targeting pdcd4 and pten, our research demonstrates that a reduction in mir- 21 is critical to increase sensitivity to 5- fu. 22072615_1 these results suggest that mir-365 can directly targetthe 3'utr sequences of both cyclin d1 and bcl-2. 22072615_2 these data support the idea that mir-365 downregulation may contribute to the overexpression of cyclin d1 and bcl-2 in colon cancer. 22072615_3 these data suggest that the antitumor effects of mir-365 may be mediated by inhibition of its targetgenes, cyclin d1 and bcl-2. 21632853_1 ectopic expression of mir-146a inhibited migration and invasion and downregulated egfr and irak1 expression in gastric cancer cells. 21632853_2 to identify whether the egfr and irak1 genes were direct target of mir-146a, we generated an egfr or irak1 3'-utr luciferase construct. 23201162_1 in crc cells, mir-137 target fmnl2 messenger rna and is regulated by the transcription factor hmga1. because mirnas are believed to function by inhibiting translation of their mrna target, these observations imply that mir-137 might be a negative regulator of fmnl2. 23201162_2 the results make it evident that mir-137 affects fmnl2 expression by directly binding to the 3' utr region of fmnl2 and validate that fmnl2 is a direct target of mir-137. 23201162_3 these data clearly substantiate that down-regulation of mir-137 contributes to enhanced fmnl2 expression, cell proliferation, and invasiveness in vitro. 23201162_4 based on these results it would be reasonable to conclude that mir-137 inhibits tumor growth and metastasis in vivo by down-regulating fmnl2. 23201162_5 these results suggest that hmga1 up-regulates the level of mir-137 and consequently affects the functions of the mir-137-揊mnl2 pathway in crc cells. 23802567_1 the microarray analysis showed mrnas related to apoptosis , pi3k signalling , proliferation , invasion and enos transcription were target by mir-492 20198616_1 fscn1 as a target of mir-145, mir-133a and mir-133b. 19671678_2 using computational methods, we first predicted that fus1 is a target of three mirnas, mir-93, mir-98, and mir-197, and then showed that exogenous overexpression of these mirnas inhibited fus1 protein expression. 19671678_4 we further found that mir-93 and mir-98 are expressed at higher levels in small-cell lung cancer cell lines than in non-small-cell lung cancer cell lines and immortalized human bronchial epithelial cells , and that mir-197 is expressed at higher levels in both sclcs and nsclcs than in hbecs. 19671678_5 finally, we found that elevated mir-93 and mir-197 expression is correlated with reduced fus1 expression in nsclc tumor specimens. 22854965_1 here, we show that uv radiation induces up-regulation of mir-125b, which negatively regulates p38alpha expression through targeting it's 3'-utr. 22854965_2 our data also indicated that 3'-utr is required for mir-125b-mediated p38alpha down-regulation because expression of a p38alpha coding region construct was insensitive to mir-125b overexpression as well as uv radiation . 22854965_3 all of this body of evidence indicates that mir-125b plays a critical role in repressing p38alpha expression through targeting its 3'-utr upon uv radiation. 25312970_1 this result confirms that cav1 is a direct target of mir199a-5p in hepatocytes. 20924637_1 we found that ectopic expression of hsa-mir-128 suppressed a luciferase reporter containing the bax-3' utr and reduced the levels of bax in hek293t cells. 20924637_2 the above results suggest that hsa-mir-128 downregulates bax by different mechanisms, i.e., through mrna degradation as well as through translational repression. 20924637_3 these results strongly suggest that hsa-mir-128 directly inhibits the expression of bax by binding to its targetsequence. 26747651_1 scd and aldh3a2 were demonstrated to be direct targets of mir-192*. of note, in both 3'-utrs mutagenesis of sequence complementary to the mir-192* seed region resulted in a significant attenuation of the mirna effect, providing evidence that scd and aldh3a2 are subject to direct regulation by mir-192*. 19088079_1 mir-221 target c-kit and p27kip1 in pasmc. in this study we demonstrate that pdgf induces the expression of mir-221, which results in down-regulation of c-kit and p27kip1 in human primary pulmonary artery smooth muscle cells . 19088079_2 therefore, these results confirm that both c-kit and p27kip1 are repressed by mir-221 in pasmc, with p27kip1 inhibited at the translation step and c-kit at the mrna level. in conclusion, these results confirm that pdgf leads to down-regulation of c-kit and p27kip1 through induction of mir-221 in pasmc. 23333633_1 these results suggested that mir-182 is a major negative controller of reck in mda-mb-231 cells. 23333633_2 these data confirmed that reck is a direct target of mir-182 and inhibits reck via post-transcriptional repression. 23333633_4 regulation of reck by mir-182. 23333633_5 diagram showed the seed sequence of mir-182 at the wild type reck 3'-utr reporter and the mutant reporter containing four mutated nucleotides. 23333633_6 additionally, we also found that mir-182 targeted reck 3'-utr to repress protein expression in these cells. 21771878_1 expression of the so-called myomirs, mir-208a and 208b, has been correlated with the expression of their host genes, alphamyhc and -betamyhc . 21771878_3 at 2 days post-mi, there is a dramatic downregulation of both alphamyhc and -betamyhc mrna, and while expression of mir-208a is also decreased, mir-208b expression is unchanged. 21771878_4 in contrast, at 2 wk post-mi, mir-208b is upregulated but expression is again normalized by 2 mo post-mi, whereas expression of -betamyhc mrna is increased at both time points. 21771878_5 expression of mir-208a is normalized or downregulated at 2 wk and normalized at 2 mo post-mi, while expression of alphamyhc is consistently downregulated. 26053181_2 mir-106b directly targets rankl and regulates il-8, mmp2 and twist. 22811578_1 c-fos was found to be a target of mir-101a because overexpression of mir-101a decreased the protein and mrna levels of c-fos and its downstream protein transforming growth factor--beta1. 22811578_3 our computational analysis predicted that mir-101 has the potential to repress c-fos: the 3- -untranslated region of fos mrna contains 1 binding site for mir-101 among humans, rats, and mice. 22811578_4 previous study has experimentally identified human fos mrna as a target of mir-101 by luciferase assay. in this study, we first confirmed the regulation of rat and mousefos by mir-101a by luciferase assay. 22811578_5 these data suggest that c-fos and its downstream protein tgf-beta1 play an important role in mir-101a-搈ediated suppression of cf proliferation. 22139444_1 these results suggest that mir-30c acts as a tumor suppressor and negatively regulates endometrial cancer cells by targeting mta1. 22139444_2 our study showed that overexpression of mir-30c leads to the down-regulation of mta1 both at the mrna and protein levels. 22139444_3 together, mir-30c suppresses cell proliferation and invasion partly by reversely regulating mta1 expression. 22139444_4 figure 2. mir-30c target 3'-utr of mta1. 24880483_1 overexpression of mir-1246 promoted uvb-induced apoptosis, while knockdown of mir-1246, using a specific inhibitor, resulted in a significant reduction in uvb-elicited apoptosis. 24880483_2 we further demonstrate that mir-1246 negatively regulated the expression of rtkn2 through binding to the 3'-untranslated region of rtkn2 at the posttranscriptional level. 24880483_3 moreover, rtkn2 was observed to be resistant to uvb-induced apoptosis and rtkn2 antagonized the pro-apoptotic effects of mir-1246 during uvb-induced apoptosis in hacat cells. 23507142_1 igf1r is a direct target of mir-16 in os cells. 23507142_2 furthermore, we confirmed that igf1r is a direct target of mir-16. 23904268_1 mir-29b represses cdk2 translation through direct interaction with the cdk2 mrna via its 3'-untranslated region , whereas point mutation of mir-29b binding site in the cdk2 3'-utr prevents mir-29b-搃nduced repression of cdk2 translation. 23904268_2 moreover, mir-29b directly interacts with the cdk2 mrna via its 3'-utr and to repress cdk2 translation. 23904268_3 taken together, these results indicate that mir-29b interacts with the cdk2 mrna via its 3'-utr, thus repressing cdk2 translation. 26845446_1 these results indicate that mir-133a binds directly to the 3'-utr of igf-1r, consequently inhibiting igf-1r expression 21266077_1 mir-34a overexpression results in the downregulation of map3k9. 21266077_2 as illustrated in additional file 3, figure s3, co-transfection of psi/mir-34a with mature mir-34a mimics did not decrease luciferase activity relative to the negative control. 21266077_3 negative results for these experiments were obtained at different time points and with two cell lines , indicating that either the mir-34a affect on map3k9 is not a direct effect, or that there is some conformational structural difference between the 3' utr of the reporter versus the native 3' utr, which inhibits mir-34a targeting of the reporter. 18973228_3 this property has been addressed for mir-9 and mir-125a, whose rescued expression promoted medulloblastoma cell growth arrest and apoptosis while targeting the proproliferative truncated trkc isoform. in conclusion, misregulated microrna expression profiles characterize human medulloblastomas, and may provide potential targets for novel therapeutic strategies. 26746193_1 to confirm the active target site of mir-150, the 39 utr of slc2a1 was cloned into a luciferase reporter vector, which was then subjected to targeted mutagenesis to alter the seed site and disrupt mir-150 binding . 26746193_2 slc2a1 is a target of mir-150 in t cells 23353818_2 in addition, the detection of mir-296-5p and expression of cdx1 in primary gc tissues and adjacent im tissues revealed that mir-296-5p is inversely correlated with cdx1, further supporting our in vitro results. 19258450_1 the reduction of mir-34a expression in organotypic tissues derived from hpv-containing primary human keratinocytes correlates with the early productive phase and is attributed to the expression of viral e6, which destabilizes the tumor suppressor p53, a known mir-34a transactivator. 21270667_1 mir-101 inhibits cell proliferation and invasion and enhances paclitaxel-induced apoptosis in nsclc cells, at least in part, by directly repressing ezh2 expression. 26655730_1 the results demonstrated that mir-21 and its targets were co-expressed in pancreatic islet structures and that target gene expression was negatively regulated by mir-21 . 23519249_1 overexpression of mir-491-5p in the pancreatic cancer cell line sw1990 effectively inhibited both endogenous bcl-xl and tp53 gene expressions. 23184950_1 the pattern ofegr1 expression was the opposite of the mmu-mir-7578 expression pattern following lps induction , suggesting that up-regulation of mmu-mir-7578 may repressegr1 expression. 23184950_2 these data indicate that mmu-mir-7578 regulates egr1 expression both on mrna and protein levels. 23184950_3 taken together, the above data suggest that mmu-mir-7578 directly targets egr1 and represses its expression mainly by binding to mrea and mreb within its 3'-utr, but mrec does not make a significant contribution to mmu-mir-7578 recognition. 23184950_4 these observations demonstrate that egr1 down-regulation by mmu-mir-7578, as in egr1 ablation, inhibits the expression of tnfalpha and il6. 20656682_2 d3 up-regulated protein 1 is regulated by foxo3a and mir-17-5p at the transcriptional and post-transcriptional levels, respectively, in senescent fibroblasts. 20842113_1 to verify whether hdac4 is a direct target of mir-22, a dual-luciferase reporter system was used by co-transfection of mir-22 and a luciferase reporter plasmid containing the 3- utr of human hdac4. 20842113_2 as shown in figure 5b, the luciferase activity was significantly inhibited by mir-22 co-transfection, and further mir-22 failed to inhibit the expression of luciferase construct on target site deletion, suggesting that mir-22 can directly target the 3- utr of hdac4. 20842113_3 moreover, in hcc hep3b and smmc7721 cells, endogenous expression of hdac4 protein was suppressed by mir-22 transfection , further proving that hdac4 is directly targeted and regulated by mir-22 expression. 20842113_4 this result further confirms that endogenous hdac4 is regulated by mir-22 and mir-22 downregulation may participate in hcc carcinogenesis and progression through potentiation of hdac4 expression. 20842113_5 this result further suggests that mir-22 may suppress hcc cell proliferation at least partially through targeting hdac4 expression. 25961460_1 mir-26a markedly repressed the luciferase activity of the acsl3, acsl4, gsk3b, pkcd, pkcq, pck1, and tcf7l2 constructs . 25961460_2 mutation of the mir-26a target sites abrogated mir-26a-揳ssociated repression in luciferase activity, suggesting a direct interaction of mir-26a with these sites. 25961460_3 these data demonstrate that mir-26a directly targets several key genes crucial for insulin signaling and metabolism of lipid and glucose, including acsl3, acsl4, gsk3b, pkcd, pkcq, pck1, and tcf7l2. 23142217_1 our data show that the mir-15b mimic targets the predicted binding site within the nrp-2 mrna 3'-utr, as it decreased the luciferase in 9l cells transfected with a luciferase reporter vector containing the predicted binding site. 23142217_2 western blot analysis revealed that nrp-2 expression was significantly decreased by mir-15b mimic transfection, and mmp-3 expression was significantly decreased by mir-152 mimic transfection. 23142217_3 co-transfection of mir-15b and mir-152 mimic significantly decreased both mmp-3 and nrp-2 expression. 23142217_4 hese data show that mir-15b and mir-152 directly bind to their respective predicted binding sites in the nrp-2 and mmp-3. 22190470_1 a guanine-to-cytosine mutation at the 3'-utr of cd274 mrna led to cd274 overexpression by disrupting the mir-570 binding. 22190470_2 this indicated potential mir-570-mediated regulation of cd274 expression. 22190470_3 these findings indicate that mir-570-mediated repression is specific to the cd274 gene. 22190470_4 these findings suggest that the mutation in cd274 3'-utr is directly involved in posttranscriptional regulation mediated by mir-570. 22190470_5 furthermore, endogenous mir-570 was detected by rt-pcr analysis in both gastric cancer and normal tissues suggesting that mir-570 may be involved in cd274 translational inhibition . in summary, our work demonstrated that cd274 overexpression was contributed via a frequent somatic mutation in cd274 3'-utr by disrupting posttranscriptional and translational controls mediated by mir-570. 26872014_1 therefore, real-time pcr and western blots analysis were performed to test whether mir-361-5p could regulate cxcr6. 26872014_2 as expected, mrna and protein levels of cxcr6 were reduced in hepg2 cells with mir-361-5p overexpression. 26872014_4 however, mutation of the mir-361-5p target site abrogated mir-361-5p-mediated reduction in luciferase activity . 25943633_1 cdc-27 is a direct target of mir-27a and its downregulation conferred increased radioresistance of the cells. 25943633_2 these results suggest that mir-27a can directly target cdc27 and regulate its expression in tnbc cells. 25943633_3 these results suggest that mir-27a can modulate radiosensitivity of tnbc cells through targeting cdc27. in this study, we verified a highly conserved putative binding site between mir-27a and cdc27 and demonstrated that mir-27a can directly regulate cdc27 expression in tnbc cancer cells. 26589417_1 luciferase assay showed that metadherin mrna was a direct target of mir-30a-5p. 26589417_3 we found that mir30a-5p could target mtdh 3'-utr, and ectopic mir-30a-5p expression with special mimics could degrade its protein and mrna. 26362716_1 we also found that ets1 was a mir-506 target, and it was expressed in 71.10% of gastric cancer tissue samples. 26362716_2 collectively, these results indicate that ets1 may be a potential target mediating mir-506edependent regulation in gastric cancer cells. 26362716_3 we also demonstrated that ets1 is a direct target of mir-506. 21709669_1 the proposed interaction between mir-148a and the 3' untranslated region of cdc25b was verified by in-vitro luciferase assays. 21709669_2 these data confirm the direct interaction between mir-148a and the 3'-utr of cdc25b mrna. 21709669_3 concordant with our earlier results, we observed that the over-expression of mir-148a suppressed the endogenous cdc25b protein level in imim-pc2 cells below the detection limit . 21709669_4 further, our results for the first time demonstrate that cdc25b is a direct target of mir-148a. 26203557_1 these results confirmed that both subunits prkar1a and prkacb are direct targets of mir-200c. 20619502_1 taken together, these findings demonstrate that app is a target of mir-16 and the abnormally low expression of mir-16 could potentially lead to app protein accumulation in ad mice. 20619502_2 so, among these hypothesized mirnas, at least mir-16 may directly regulate app levels. 20619502_3 thus, mir-16 negatively target app in the 3' utr and inhibits app mrna translation, which in turn affects app protein translation rather than degradation of app mrna. 22370637_1 we demonstrate that bmf is a target of mir-34c-5p, and that its silencing, together with that of c-myc, a known target of mir-34c-5p, contributes to resistance to apoptosis induced by paclitaxel through p53 downregulation. 20451497_1 using luciferase reporter assays with 3'-utrs of tbp, over-expression and inhibition of mir-146a, we showed that mir-146a target tbp. 20451497_2 this result confirms that mir-146a target tbp. 20451497_3 since mir-146a is down regulated in sthdh/hdh cells, it is expected that endogenous expression of tbp would be higher in these cells. 20451497_4 expression of endogenous tbp in mrna as well as protein level was decreased in sthdhq111/ hdhq111 cells expressing exogenous mir-146a . 20451497_5 taking together all this data, we experimentally show that tbp is one of the target of mir-146a. 25959411_1 bioinformatics analysis with luciferase reporter assays demonstrated that wnt11 3'-utr was a new direct target of mir-154-5p. 25959411_2 taken together, these results demonstrate that, under tensile stress, mir-154-5p negatively regulates adscs osteogenic differentiation through the wnt/pcp pathway by directly targeting wnt11. 25959411_3 the dual luciferase reporter assay in 293 t cells and the gfp/rfp reporter assay in adscs confirmed that wnt11 was a direct target of mir-154-5p. 25959411_4 these results confirm that wnt11 is a direct target of mir-154-5p. 20368621_1 we further show that mir-137 post-transcriptionally represses the expression of ezh2, a histone methyltransferase and polycomb group protein. 20368621_2 furthermore, targeting of ezh2 by mir-137 was specific because mutating the seed sequence targeted by mir-137 within the luciferase-ezh2-3'utr reporter alleviated mir-137-mediated suppression . 20368621_3 together, these data demonstrate that the effect of mir-137 on ezh2 protein expression is repressive, post-transcriptional, and specific. 20368621_4 importantly, they also suggest that ezh2 is a functional target of mir-137 in the context of adult neurogenesis. 23894385_1 we also found that several mirnas suppressed sdf-1alpha protein expression, while just mir-27a and mir-27b directly bound to the sdf-1alpha 3'utr. 23894385_2 as expected, mir-27a- and mir-27b-mediated suppression of the firey/renilla luciferase activity was abolished when we mutated the mir-27a and mir-27b binding sites in the sdf-1alpha-3' utr , suggesting that mir-27a and mir-27b inhibit sdf-1alpha translation by directly binding to the sdf-1alpha 3' utr. 23894385_3 thus, we performed mutation assays of the putative binding sites to confirm that the sdf-1alpha 3' utr is a direct target of mir-27a and mir-27b . 16966691_1 the overexpression of mir-21 is strongly associated with both a high ki67 proliferation index and presence of liver metastasis. 25480585_1 western blotting showed that the expression of foxo3a was significantly elevated in snk-6 cells with mirna-155 inhibition. it was concluded that reduction in mirna-155 expression can inhibit the proliferation of snk-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of foxo3a gene. 26482036_1 ppargamma is known to be targeted by mir-20a. 26587974_1 rescuing mir-26a expression also inhibits ezh2, n-cadherin, vimentin, and snail expression and induces e-cadherin expression both in vitro and in vivo. 26587974_2 ezh2 is the direct molecular target of mir-26a. 26587974_3 these results suggest that mir-26a can bind to the 3'-utr of ezh2, and that ezh2 may be a downstream target of mir-26a in ec cells. 26587974_4 our in vitro studies suggested that ezh2 is the direct downstream target of mir-26a; therefore, we examined ezh2 protein expression in tumor tissues using ihc. 18596100_2 mir-100 and mir-101 were chosen for further analyses based on their reproducible changes in expression after infection and on the basis of having predicted targets in the 3' untranslated regions of genes encoding components of the mammalian target of rapamycin pathway, which is important during hcmv infection. 18596100_3 together,mir-100 and mir-101 reduced mtor protein levels. 19017354_2 figure 7. mir-223 target lmo2 mrna. 19017354_3 to demonstrate a direct interaction between the 3'-utr of lmo2 mrna with mir-223, we inserted the 3'-utr region predicted to interact with this mirna into a luciferase vector prl-tk. 19017354_4 a 50% reduction in relative luciferase activity was observed when nih-3t3 cells were co-transfected with the mir-223 precursor and the reporter plasmid containing the 3'-utr sequence of lmo2 mrna . 19017354_5 these results indicated that mir-223 target the 3'-utr sequence of lmo2 mrna in vitro. 25605245_1 furthermore, anti-mir196b up-regulated fas expression and increased apoptosis in colorectal cancer cell lines. 25605245_2 our results suggest that the up-regulation of mir196b modulates apoptosis in colorectal cancer cells by partially repressing fas expression and that anti-mir196b could be a potential candidate as an anti-cancer drug in colorectal cancer therapy. 19148830_1 the pri-mir-17-92 polycistron encodes micro-rnas , which decrease e2f1 protein expression, regulating proliferation and/or apoptosis. 19148830_3 lentiviral-mediated overexpression of nkx2-5 in the t-all cell line molt-4 consistently resulted in increased mir-17-92 pri-mirna levels and decreased amounts of e2f1 protein. 19148830_4 induction of apoptosis by treating mir17-92 or e2f1 transduced t-all cells with etoposide led to reduced or enhanced cell viability, respectively. 23111103_1 functionally, mir-429 overexpression suppressed cell apoptosis by directly targeting sox2 in ht-29 cells. 21609717_1 we also found that mir-98 target the 3'untranslated region of il-10 transcript. 21609717_2 to certify the possibility that il-10 was regulated posttranscriptionally by mir-98, we constructed reporter plasmids by amplifying the mouseil-10 mrna 3'-utr and cloning into xbai site of pgl3 vector. 21609717_3 fig. 2. il-10 may be molecular target of mir-98 posttranscriptional repression. 21609717_4 so, this result indicated that lps-mediated inhibition of mir-98 expression is at least partially involved in the induction of lps desensitization via up-regulation of il-10. 22334722_1 increased mir-29 expression resulted in a decrease in dnmt1, dnmt3a, and dnmt3b and antiapoptotic myeloid cell leukemia sequence 1 protein levels as shown in 1 germ cells of adult rats exposed neonatally to eb and 2 in spermatogonial gc-1 transfected with mir-29. 22334722_2 compared with scrambled oligonucleotide, mir-29a transfection had a clear repressive effect on dnmt3a and dnmt1 protein levels, whereas mir-29a transfection had no significant effect in down-regulating dnmt3b protein levels . 22334722_3 the most marked inhibitory effect of mir-29 overexpression on dnmt protein levels was observed for mir-29b, which highly reduced dnmt3a and dnmt3b protein levels as well as, to a lesser extent, dnmt1 protein levels . 22334722_4 transfection of mir-29c reduced only dnmt3a protein levels , because no modification was observed in dnmt3b and dnmt1 protein levels. 21750653_1 we first validated whether cdk4 was a target gene of mir-122. 21750653_2 the 3'-utr of cdk4 contains a putative mir-122 binding site . 21750653_3 to test whether the predicted binding sites in cdk4 mrna could mediate repression of translation by mir-122, the 3'-utr of cdk4 was subcloned downstream of the luciferase gene in the pgl3 control vector. 21750653_4 as shown in figure 3b, cells that were transfected with the reporter construct containing the 3'-utr of cdk4 had significantly lower luciferase activity after the cells cotransfected with the mir-122 mimic compared to cells that were cotransfected with control rna. 21750653_5 these results indicate that the up-regulation of the mir-122 target gene cdk4 is essential for psmd10 accumulation in mir-122 inhibitor-搕reated huh7 cells. 21750653_6 figure 4. the mir-122 inhibitor enhanced the psmd10 stability through its target gene cdk4. 21750653_7 figure 3. cdk4 was confirmed as a target of mir-122. 18986979_3 consistent with an impairment of mirna-mediated regulation of bace1 expression, these findings prompted us to investigate the regulatory role of the bace1 3'-utr element and the possible involvement of specific mirnas in cultured neuronal and fibroblastic cells. 18986979_4 through various experimental approaches, we validated computational predictions and demonstrated that mir-298 and mir-328 recognize specific binding sites in the 3'-utr of bace1 mrna and exert regulatory effects on bace1 protein expression in cultured neuronal cells. 26126865_1 a bioinformatic approach revealed ccl2 and ccl5 as potential targets of mir-98 or let-7g* . 26126865_2 taken together, these results support a potential role for gsk3-beta inhibitor-dependent mirnas, mir-98 and let-7g*, in reduction of endothelial inflammation via direct targeting of pro-inflammatory mediators, such as ccl2 and ccl5. 20856896_1 among the possible micrornas found to be upregulated in the skeletal muscle tissue of mdx compared to wt mice, we demonstrated that mir-222 specifically binds the 3'-utr of -beta1-syntrophin and participates in the downregulation of -beta1-syntrophin. 20856896_2 thus, these results demonstrate that mir-222 is expressed in skeletal muscles, and notably upregulated in mdx mice, suggesting a potential role of mir-222 in downregulating -beta1-syntrophin expression in dystrophic muscles. 20856896_3 this result strongly suggested an interaction between mir-222 and the 3'-utr of -beta1-syntrophin. 20856896_4 this result indicates that exogenous mir-222 reduces the protein level of endogenous -beta1 syntrophin, regardless of the cell origin. 20856896_5 taken together, these data demonstrate that mir-222 regulates -beta1-syntrophin protein expression, and silencing mir-222 can restore -beta1-syntrophin protein expression to normal in dystrophic cells in culture. 24388909_1 the toxins decreased the expression of microrna-122, which corresponded with an increase in two target genes: cyclin g1 and the cationic amino acid transporter cat-1. 21590770_1 we found that mir-150 was strongly elevated, whereas c-myb, a transcription factor and a target gene of mir-150, was significantly reduced in colon tissue after dss treatment. 21590770_2 interestingly, elevation of mir-150 and down-regulation of c-myb were also observed in human colon with active ulcerative colitis compared to the normal colon. 26327117_2 p300 is a positive regulator of ctnnb1 that synergistically activates ctnnb1/tcf transcription . 26327117_3 our results indicate increased expression of p300 in mir-142-null versus wild type lungs . 26327117_4 the respective increase in apc and p300 in mir-142-null lungs was also validated at the mrna level . 26327117_5 ctnnb1 mrna expression is not changed between mir-142-null and control lungs . 20627091_1 sirt1 is a target of mir-34a in endothelial cells. 20627091_2 this result indicates that the mir-34a binding site within sirt1 3'utr mediates mir-34a translational repression. 20627091_3 these results suggested that mir-34a regulates sirt1 in a posttranscriptional manner in huvec. 20627091_4 to examine if mir-34a directly bindhe 3' utr of sirt1 mrna, we transfected huvec with a luciferase reporter vector which contains the 3'utr of sirt1 and a vector which has the sirt1 3' utr mutated in mir-34a binding site. 20627091_5 this result indicates that the mir-34a binding site within sirt1 3' utr mediates mir-34a translational repression. 20627091_6 taken together these data show that mir-34a controls sirt1 expression in primary endothelial cells. 20484493_1 the mir-200 microrna family is important for maintaining the epithelial phenotype, partially through suppressing zeb1 and zeb2. 20484493_2 as a direct target of the mir-200 family, zeb1 shows an expression pattern inverse to that of the mir-200 family . 20304954_1 a luciferase reporter assay confirmed that mir-193b directly regulates ccnd1 by binding to the 3' untranslated region of ccnd1 mrna. 20304954_2 we demonstrated mir-193b represses melanoma cell proliferation and that ccnd1 is a direct target of mir-193b. 20304954_3 gene expression profiling reveals ccnd1 as one of mir-193b potential target. 20304954_4 mir-193b suppresses cell proliferation by directly down-regulating ccnd1. 20304954_5 the results showed that ccnd1 mrna and protein levels were approximately 50% lower in cells overexpressing mir-193b than in control cells . 20304954_6 the results showed that activity of the luciferase reporter gene carrying the wild-type ccnd1 3' utr on average was 30% lower in cells overexpressing mir-193b, while no repression of luciferase activity was observed in the reporter construct carrying the mutant ccnd1 3' utr . 24755409_1 moreover, deregulated expression of atg4b in cd34 cml cells inversely correlates with transcript levels of mir-34a, and atg4b is shown to be a direct target of mir-34a. 22139078_1 we found that the lphn2, basp1 and mafg genes have conserved mir-7 target sequences in their 3' untranslated region in both mouse and human mrnas . 22773691_1 luciferase reporter assays were used to determine mir-140-3p binding to the cd38 3'-utr. 22773691_2 the cd38 3'-untranslated region has target for mir-140-3p. 22773691_3 the findings indicate that mir-140-3p modulates cd38 expression in hasm cells through direct binding to the cd38 3'-utr and indirect mechanisms involving activation of p38 mapk and nf-kappab. 22773691_4 when the luciferase reporter assay studies were repeated in nih 3t3 cells, site-directed mutation of the first mir-140-3p targetcompletely reversed the luciferase inhibition by mir-140-3p mimic . 23293219_1 mir-196b was found to suppress c-myc and bcl-2 mrna expression in ecscs, and there was a significant correlation between mir-196b and hoxa10 expression in ecscs and nescs. 25871529_3 3c, insulin1 and insulin2 mrnas were both decreased in the incrna tug1 sirna-treated group. 25871529_5 real-time pcr analyses suggested that the expression levels of pdx1, neurod1, mafa and glut2 were decreased in the incrna tug1 sirna-treated group . 25997740_1 mir-335 decreased the luciferase activity of wild type pgl3-3'-utr-siah2, but not mutant pgl3-3'-utr-siah2, in various anti-cancer drug-resistant cancer cell lines , suggesting that mir-335 directly targets siah2. 25997740_2 taken together, these results suggest that mir-335 increases the expression of hdac3 by targeting siah2. 25997740_3 taken together, these results suggested that mir-335 regulates the response to anti-cancer drugs in association with its effect on siah2 and hdac3 expression. 26912776_1 the results of the luciferase reporter assay indicated that sirt1 was a target gene of mir-22. in addition, knockdown of sirt1 attenuated apoptosis in mgcs. 26912776_2 mir-22 inhibits mgc apoptosis by downregulating sirt1 directly in vitro. 26912776_3 these findings demonstrated that mir-22 targeted sites of 3'-utr region of sirt1 and that there is an inverse correlation between the mir-22 expression level and the protein expression level of sirt1. 26912776_4 therefore, sirt1 was a target gene of mir-22 and sirt1 may play an important role in the process of mir-22 affecting gc apoptosis. 23166327_1 conversely, the delivery of a mir-155 antagonist to kb cells overexpressing mir-155 resulted in increased cdc73 levels, decreased cell viability, increased apoptosis, and marked regression of xenografts in nude mice. 19514064_1 hox gene clusters play an important role during cardiac septation to valve formation in different species, and the mir-196a-hoxb8-sonic hedgehog signaling pathway is of particular interest. 19514064_2 recently, we found that a genetic variant of rs11614913 in the mir-196a2 sequence could alter mature mir-196a expression and target mrna binding; this observation led us to hypothesize that rs11614913 might influence susceptibility to sporadic congenital heart disease . 19514064_3 we conducted a three-stage case-control study of chd in chinese to test our hypothesis by genotyping mir-196a2 rs11614913 and three other pre-mirna snps in 1,324 chd cases and 1,783 non-chd controls. 19514064_4 we found that rs11614913 cc was associated with a significantly increased risk of chd in all three stages combined . in a genotype-phenotype correlation analysis using 29 cardiac tissue samples of chd, rs11614913 cc was associated with significantly increased mature mir-196a expression . in vitro binding assays further revealed that the rs11614913 variant affects hoxb8 binding to mature mir-196a. 19514064_5 this is the first study to indicate that mir-196a2 rs11614913 plays a role in sporadic chd susceptibility. 25362566_1 in order to support our data suggesting that the mir26a level may be inversely associated with il6 level in eae mice, a luciferase reporter assay was performed to determine whether mir26a could directly target the 30 utr of il6 mrna in hek293 cells. 25362566_2 r, these results strongly suggest that il6 is a direct target of mir26a in hek293 cells. 25362566_3 a significant decrease of luciferase activity was found when compared with the mir control the activity of the mt 30 utr vector was unaffected by a simultaneous transfection with mir26a. 24722426_2 subsequent experiments confirmed that mir-17, 20a, 20b could regulate the expression of tgf-betar2 at both mrna and protein levels by directly binding with 3'-utr region of tgf-betar2, so that these three mirnas could inhibit tgf-betar2 that brings about cisplatin-resistant and migration. 24722426_3 these results suggested that mir-17, 20a, 20b binds directly to putative tgf-betar2 3'-utr regions, as predicted by the in silico model. 18185590_2 a p15as expression construct induced p15 silencing in cis and in trans through heterochromatin formation but not dna methylation; the silencing persisted after p15as was turned off, although methylation and heterochromatin inhibitors reversed this process. 24148619_1 in ileal biopsy samples of patients with cd, there was an inverse correlation between levels of mir30c and mir130a and those of atg5 and atg16l1, supporting in vitro findings. 24148619_2 inhibition of mir30c and mir130a in cultured intestinal epithelial cells and in mouse enterocytes blocked aiec-induced inhibition of atg5 and atg16l1 expression and restored functional autophagy. 26464441_1 to test whether ski2-4/rdr6 generally accumulated endogenous 5'-cleavage fragments generated by risc cleavage, we analyzed four mirna targets by northern blotting, lom2 , ago1 , myb33 and csd2 . 20351277_1 here we show that overexpression of mir-155 significantly down-regulates the core mmr proteins, hmsh2, hmsh6, and hmlh1, inducing a mutator phenotype and msi. 20351277_2 hmlh1, hmsh2, and hmsh6 are target of mir-155. 20351277_3 these results are qualitatively similar to the luciferase-based system containing the mir-155 seed sequence from hmlh1 and hmsh6 , and suggest that mir-risc ribosome displacement is unlikely to be an issue in mir-155 modulation of mmr proteins. 20351277_4 these results suggest that mir-155 exerts its greatest affect on mmr proteins by posttranslational inhibition, a common characteristic of mir regulation . 20351277_5 together with the findings of the tissue array studies, these results strongly suggest that mir-155 overexpression in human tumors results in down-regulation of the core mmr proteins hmlh1 and hmsh2. 23497288_1 our findings suggest that mir-125b may play a role in the development of chemoresistance in ews by suppressing the expression of the apoptotic mediators, such as p53 and bak. 24752578_1 results demonstrated that mir-22 well paired with the 3'-utr of hmgb1 downregulated the hmgb1 expression and blocked the hmgb1-mediated autophagy during chemotherapy in osteosarcoma cells in vitro. 20966078_1 in the present study, we demonstrated by a luciferase reporter assay that mir-491-5p down-regulated the luciferase activity through a binding site in the 3' utr of par-3. 20966078_2 although the luciferase reporter assay was useful in evaluating the effect of mir-491-5p on regulating par-3 expression, it is important to demonstrate that mir-491-5p can regulate the expression of endogenous par-3. to ensure the effect of mir-491-5p on par-3 expression was not specific to nrk52e cells, we transfected gfp-tagged mir-491-5p in human proximal tubular epithelial cells and demonstrated that mir-491-5p, too, significantly down-regulated par-3 expression . 20966078_4 4f, mir-491-5p significantly decreased the mrna level of par-3, suggesting that mir-491-5p regulates par-3 expression through promoting par-3 mrna degradation. 20966078_5 this data indicated that in the fibrotic kidney, mir-491-5p induction was correlated with down-regulation of par-3 expression. 25639535_1 mir-200b expression in breast cancer: a prognostic marker and act on cell proliferation and apoptosis by targeting sp1. 20728471_1 compared to experimental controls, mir-199a-3p and mir-210 efficiently reduced hbsag expression without affecting hepg2 2.2.15 cell proliferation. 20728471_3 bioinformatics analysis indicated a putative binding site for mir-199a-3p in the hbsag coding region and a putative binding site for mir-210 in the hbv pre-s1 region. 25868147_1 after successfully validating arhgef12, fgf12, and adcy5 as myocd cernas that regulate myocd levels in a mirna-dependent manner, we investigated their association with the myocd-targeting mirnas used here. 25868147_5 expression of i-mir-34c-5p, i-mir-539-5p, i-mir-431-5p, i-mir-3651, and i-mir-758-3p significantly reduced luc-arhgef12, luc-fgf12, and adcy5-3'-utr activities in smcs . 26101709_1 dual-luciferase assays confirmed that mir-520d-5p directly targeting cthrc1 and sp1 transactivate mir-520d-5p by binding to its upstream promoter region. 26101709_2 mechanically, mir-520d-5p directly targeted cthrc1 and could be regulated by specificity protein 1 . 26101709_3 in summary, our findings revealed that mir-520d-5p reversely regulated cthrc1 by directly targeting its mrna 3'-utr. 26101709_4 taken together, the above studies indicate that mir-520d-5p may play a role in the emt of crc by inactivating the phosphorylation of erk1/2 via directly targeting cthrc1. 22058146_2 mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase casp3. 21757686_1 consistent with these findings, ezh2 was down-regulated by let-7b and less so by the other mirnas . 21757686_2 significantly, the use of a let-7b antagonist reversed the effect of kdm2b depletion on ezh2 suggesting that a kdm2b-let-7b axis regulates ezh2 levels in mefs. 21757686_3 e2f2 levels decline during senescence , and in line with previous studies of let-7/98 targets , we found that e2f2 expression was also suppressed by let-7b . 21757686_4 importantly, overexpression of kdm2b potently increased the expression of e2f2 , as well as that of c-myc, an additional let-7b target . 21757686_5 therefore, kdm2b function in growth control and ezh2 regulation extends beyond the bypass of senescence in primary cells through a mechanism associated with regulation of let-7b mirna. 23383034_3 additionaly, mir-30a-5p directly targeting sept7 was identified by the reporter gene assay. 20381459_1 collectively, our study demonstrates that over-expression of mir-650 in gastric cancer may promote proliferation and growth of cancer cells, at least partially through directly targeting ing4. 20381459_2 mir-650 directly inhibits the expression of ing4 through the ing4 3'utr. 20381459_3 taken together, these data imply that mir-650 may attenuate the expression of ing4 by directly targeting the ing4 3'utr. 24999188_1 in our study, mir-145 was shown to directly target igf-ir 3'-untranslated region in human bladder cancer cells. 24999188_2 small interfering rna - and mir-145-mediated igf-ir knockdown experiments revealed that mir-145 promotes cell apoptosis, and suppresses cell proliferation and migration through suppression of igf-ir expression. 19887623_2 mir-129-3p and mir-129-5p suppressed the expression of a luciferase vector with the sox4 3'-utr. 19887623_3 moreover, inhibition of mir-129-3p or mir-129-5p by antagomirs slightly enhanced the expression of sox4, suggesting that this gene is a direct target of mir-129-2. 19887623_4 taken together, the observation indirectly indicates that these epigenetic treatments may lead to reactivation of mir-129-2, which in turn represses the expression of sox4. 19887623_5 taken together, these in vitro studies suggest that mir-129-2 negatively regulates sox4 and that promoter hypermethylation of this mirna derepresses its expression. 19887623_6 transient transfection of these cells with either mir-129-3p or mir-129-5p resulted in reduction of both sox4 mrna and protein . 22841474_2 combination of bioinformatics, dual-luciferase reporter assay, mass spectrometry, and western blot analysis revealed that caspase-2 and sirtuin 1 are the direct targets of mir-34a. 26018509_1 the potential regulatory function of mir-106a* on irs-2 was determined at both mrna and protein levels. 26018509_2 as shown earlier, the overexpression of mir-106a* affected the proliferation, cycle, and apoptosis of rcc a498 cells, and irs-2 was validated as a direct target of mir-106a*. 26018509_3 mir-106a* suppressed the akt signaling pathway by targeting irs-2 in rcc a498 cells. 26320176_1 mechanistically, we validated traf6 as a direct functional target of mir-146b-5p and found that mir-146b-5p overexpression significantly decreased phosphorylated tak1 and i魏balpha, the pivotal downstream effectors of traf6. 26320176_2 to our knowledge, however, it is not reported whether mir-146b-5p suppresses glioma cell proliferation and induces apoptosis through directly targeting traf6. 26320176_3 we further demonstrate that traf6 is a direct functional target of mir-146b-5p in gliomas and silencing of traf6 may mimic the above anti-tumor effects of mir-146b-5p. 23720784_1 moreover, the effects of mir-218-2 on thyroid cancer cells were due, at least partially, to targeting pdgfra and plcg1. 23720784_2 as a whole, these data suggest that pdgfra and plcg1 are direct targets of mir-218. 23720784_3 together, these data implicate pdgfra and plcg1 as functionally relevant targets of mir-218-2 in thyroid cancer. 23720784_4 here,we found that pdgfra and plcg1 were direct targets of mir-218 and associated with its effects. 16236258_2 while hsa-mir-29a and 29b target the nef gene, hsa-mir-149 targets the vpr gene, hsa-mir-378 targets env, and hsa-mir-324-5p targets the vif gene. 22533346_1 microrna-143 target macc1 to inhibit cell invasion and migration in colorectal cancer. 22533346_3 using both in silico prediction and western blot assay, we found the previously reported tumor suppressive mir-143 targeted macc1 in crc. the direct interaction between them was confirmed by 3' utr luciferase reporter gene. 22533346_4 these results suggested mir-143 could inhibit macc1 expression at transcriptional level. 22533346_5 taken together, these results indicated that mir-143 functions as a potent tumor suppressor through regulating macc1 expression. 22533346_6 we also observed an inverse correlation between mir-143 and macc1 expression in crc tissues and their adjacent normal tissues . 21029862_2 however, our data demonstrate that jpx upregulation is developmentally regulated to correlate with xist upregulation, and that jpx significantly escapes xci.our data argue that jpx is an activator of xist.therefore, 21029862_3 jpx serves an essential function and precludes xist induction when deficient. 25633534_1 overexpression of mir-375 inhibited sp1 expression by targeting the 3' untranslated region of the sp1 transcript. 23728339_1 computational prediction with targetscan software revealed that an evolutionarily conserved region in the erg 3'-utr mrna has a perfect complementary matching region to the seed sequence of the mir-30 family .to 23728339_2 examine whether mir-30 attenuates erg expression through direct targeting of the predicted 3'-utr region, a 42-base pair fragment of the erg 3'-utr containing the wild-type or mutant mir-30 binding site were constructed downstream of the luciferase gene in a reporter plasmid . 23728339_3 293t cells were transfected with the utr-reporter plus the negative control mirna , mir-30a or mir-30b.only 23728339_4 transfection of mir-30a and mir-30b with the wild-type utr-reporter led to a significant decrease of luciferase activity whereas coexpression of the antagomirs of mir-30 has no effect on the reporter activities . 22969914_2 and western blot analysis data indicated that the overexpression of mir-497 resulted in the down-regulation of bcl-w at the mrna and protein levels. 26919240_1 using an in silico approach and a luciferase reporter system, we identified and functionally validated the baculoviral iap repeat-containing 6 gene , which encodes the anti-apoptotic factor apollon/bruce, as a target of mir-342. 26919240_2 mir-342 targets the anti-apoptotic gene birc6 in hcc1937 cells. 26919240_3 this result confirmed that the pro-apoptotic function of mir-342 is strictly dependent on the presence of mutated brca1 and suggested that additional mirna targets may be involved in the establishment of the synthetic lethal phenotype. 26919246_2 in addition, the results of the qpcr and western blot analysis demonstrated that transfection with mir-200b mimics significantly reduced the mrna and protein expression levels of bmi1 in hcc cells. 26919246_3 taken together, these results indicate that bmi1 is a direct target gene of mir-200b and can be negatively regulated by mir-200b. 26095675_1 when mir-141 was overexpressed in cmec and cmt28, by transfecting with a higher concentration, it caused further reduction in luciferase expression thereby silencing 3'-utr target and validating mir-141 cdkn2a target binding . 26095675_2 additionally, this experimental evidence suggests that lack of mir-141 mediated silencing in the cmt28 cell line was permissive for p14arf mrna expression leading to the discovery of the longer 3'-utr sequence containing the mir-141 target site in these cells. 20630862_2 the let-7 family target recognition sequence in the il-13 3'-utr is highly conserved across mammalian species . 20630862_3 moreover, all mouse let-7 mirnas are predicted to target il-13 . 20630862_6 together, these studies indicated that both human and mouse il-13 are targets of let-7a and that this mirna can be specifically inhibited by an lna. 20630862_7 identical experiments were performed using the human il-13 3'-utr, human let-7a and the same lnas and produced identical results . 26722316_2 rt-qpcr analysis of sirt1 mrna expression in the pc-3 cells transfected with mir-34a. 26722316_3 western blot analysis of sirt1 expression in the pc-3 cells transfected with mir-34a 20198305_2 furthermore, in our study, an inverse relationship between the expression of hsa-mir-34c and c-met was identified in 10 paired fresh samples from tumor tissues and adjacent normal tissues. 20198305_3 infection of hsa-mir-34c mediated by lentivirus suppressed the expression of c-met directly. 20198305_4 in addition, introduction of c-met cdna lacking 3'-utr largely abrogated hsa-mir-34c-induced cell growth and invasion inhibition. 20198305_5 these findings suggest aberrantly down-regulated hsa-mir-34c is a critical factor that contributes to malignancy in human laryngeal carcinoma by a mechanism involving targeting of c-met. 22504094_1 mir-375 inhibits autophagy by reducing expression of atg7 and impairs viability of hcc cells under hypoxic conditions in culture and in mice. 21885853_1 in our previous work, we studied the role of mir-33 in regulating abca1 and cellular cholesterol efflux and were motivated to do so by its intriguing genomic location . 21885853_2 transfection of human macrophages with mir-758 but not a control mirna or other mirnas strongly decreased the stimulation of abca1 protein expression . 21885853_3 mir-33 was used as a positive control for inhibition of abca1 expression . 21885853_4 mir-758 also repressed abca1 protein in mouse peritoneal macrophages and hepatic cell lines , indicating that its effect is not cell type specific. 21885853_5 notably, inhibition of endogenous mir-758 by anti-mir-758 increased the expression of abca1 in macrophages and hepatic cells , suggesting a physiological role of mir-758 in regulating the expression of this transporter. 21885853_7 mir-758 markedly repressed the activity of the abca1 3'-utr reporter construct . 21885853_8 specific site-directed mutations in site 2, which is widely conserved among several species, abolishes the mir-758 repression of abca1 3'-utr activity, suggesting that this site is the most important in the posttranscriptional repression of abca1 by mir-758 . 19782034_2 here we show that hif1 regulates the expression of mir-210 in a variety of tumor types through a hypoxia-responsive element. 19782034_4 by argonaute protein immunoprecipitation, we identified 50 potential mir-210 targets and validated randomly selected ones. 19782034_6 when human head and neck or pancreatic tumor cells ectopically expressing mir-210 were implanted into immunodeficient mice, mir-210 repressed initiation of tumor growth. 26919869_1 taken together, our results showed that mir-27b-3p could regulate the expression of bmal1 at the posttranscriptional level by directing targeting its 3'utr. 25333261_1 metadherin was subsequently identified as a direct target of mir-145, and was found to be significantly up-regulated in hgsoc. 25333261_2 furthermore, metadherin , an oncogene that was highly expressed in breast cancer and ovarian cancer , was identified as a direct target of mir-145. 25333261_3 taken together, these results indicate that mtdh is a direct downstream target of mir-145 and mtdh overexpression in hgsoc may be attributed to the reduced expression of mir-145. 25333261_4 we showed that mtdh was directly targeted by mir-145. 21857907_1 next, we evaluated whether overexpression of mir-34a resulted in decreased sirt1 at the protein level. 21857907_2 sirt1 protein was significantly decreased after mir-34a overexpression , suggesting that the effect of mir-34a on the number of postmitotic neurons and neurite elongation might be mediated by sirt1. 21857907_3 these results suggested that the effect of mir-34a on the percentage of postmitotic neurons was not mediated by sirt1. 21857907_4 these results support the observation that mir-34a may modulate neurite outgrowth by targeting sirt1. 21857907_5 importantly, a similar increase in acetylated p53 was observed after mir-34a overexpression, suggesting that mir-34a may increase p53 acetylation and subsequent p53 transcriptional activity due to decreased sirt1 expression. 22768249_1 mir-125a inhibits the proliferation and metastasis of hcc by targeting mmp11 and vegf-a. 22768249_2 mir-125a directly down-regulated the mmp11 and vegf-a. 22768249_3 instead, luciferase reporter assays confirmed that mmp11 and vegf-a, but not other genes tested, were targets genes of mir-125a. 23426183_1 subsequent experiments demonstrated that mir-487b directly targeted suz12, bmi1, wnt5a, myc, and kras. 23426183_2 collectively, these experiments suggested that mir-487b modulates suz12, bmi1, and wnt5a via post-transcriptional mechanisms in cultured normal respiratory epithelia and lung cancer cells. 23426183_3 suz12, bmi1, and wnt5a are direct targets of mir-487b. 25645925_1 mir-155 regulates the extent of p53 activity in mature b cells by targeting socs1. 25645925_2 these data confirmed that socs1 regulates p53 activity in b cells undergoing the gc reaction. 20935646_1 we confirmed the functional relevance of the predicted overlapping binding sites for mir-96 and mir-182 by mutating the sequence from gugccaaa to gacgguaa. 20935646_3 these experiments identified foxo1 as a target of mir-182 in activated helper t lymphocytes. 20935646_4 in these cells, foxo1 was targeted only by mir-182 but not by mir-96, which was not expressed. 20935646_5 we quantified foxo1 mrna and mir-182 in activated mouse and human helper t cells. 20935646_6 as expected, mir-182 and foxo1 mrna showed a negative correlation in mouse helper t cells and human helper t cells , with increasing mir-182 and decreasing foxo1 mrna over time. 20935646_7 to further confirm the interaction of mir-182 and foxo1, we inhibited mir-182 by using locked nucleic acid oligomers10 or antagomir oligonucleotides; each bound and inhibited the mature mirna. 20935646_8 figure 2 foxo1 is a target of mir-182. 26592823_2 we validated app as the target gene of mir-16. 26592823_3 our bioinformatics analysis indicated that within the 3'-utr of the app gene, there is a putative binding site for mir-16. 22871591_1 luciferase reporter assays revealed runx2 as the direct target of mir-204 by overexpression of mir-204 on the wild-type or mutant 3'-utr sequences of runx2 in vsmcs. 22871591_2 our study has shown that down-regulation of mir-204 may contribute to b-glycerophosphate-induced vsmc calcification through regulating runx2. 22871591_3 these results indicate that mir-204 plays a negative role in vsmc calcification through down-regulating runx2 protein levels. 22871591_4 in conclusion, this study identified mir-204 as an important regulator of vsmc functions by repressing its targetgene runx2 and inhibiting medial artery calcification in vivo, which represents a novel mechanism regulating vascular calcification. 26585487_1 then luciferase reporter assay was performed to identify whether the 3'utr of foxc1 mrna was a binding target of mir-4792. 26585487_2 this result suggested that foxc1 is indeed a direct target of mir-4792. 26585487_3 up-regulation of mir-4792 led to a significant decrease in foxc1 mrna, and the down-regulation of mir-4792 obviously increased the expression level of foxc1 mrna. 26585487_4 as detected by western blot, high expression of mir-4792 obviously decreased the foxc1 protein expression compared to the control. 17681183_1 aberrant expression of mir-21 can contribute to hcc growth and spread by modulating pten expression and pten-dependent pathways involved in mediating phenotypic characteristics of cancer cells such as cell growth, migration, and invasion. 25483817_1 in order to further examine the underlying mechanisms by which mir-145 regulates emt, a luciferase reporter assay was performed to determine whether mir-145 targeted oct4. 25483817_2 furthermore, in order to determine whether mir-145 affected the expression of oct4, a549 cells were transfected with the mir-145 mimic and the mir- 145 inhibitor. 25483817_3 western blot analysis revealed that oct4 protein expression was significantly decreased in the mir-145 mimic group compared with that of the control group, while oct4 was significantly increased in the mir-145 inhibitor group . 20418948_1 a dual-luciferase reporter assay demonstrated that the 3'utr of e2f2 and ccnd2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of e2f2 and ccnd2. 20418948_2 greater than 30% reduction of luciferase activity was observed with wild-type ccnd2 and ,50% reduction of luciferase activity was observed with wild-type e2f2 . 20418948_3 these data support that e2f2 and ccnd2 are direct target of let-7a and endogenous let-7a in hek293a has no interference to our experience. 20418948_4 these data support that let-7a down-regulating the mrna expression of e2f2 and ccnd2 and repress protein translation of them. 26418898_1 the overexpression of mir-146b, but not of mir-146a,the protein and mrna levels of mat2a were diminished by mir-146b but not by mir-146a transduction. 26418898_4 our data suggest that mir-146b down-regulation is critical to the enhanced nf-kappab activity and mat2a induction in tamr-mcf-7 cells. 23126531_1 we show for the first time that cyclin g1, a mir-122 target gene, has regulatory effects on hcv replication and that alcohol increases hcv replication by regulating mir-122 and cyclin g1. 21969366_2 cyclin d1 which also promotes g1 progression, is a direct target of let-7e and we show that cyclin d1 expression is suppressed in jarid1b knockdown cells. 21969366_3 taken together, these results indicate that let-7e regulates cyclin d1 protein levels in breast tumor cells. 21969366_4 taken together, these results provide evidence that cyclin d1 is a direct target of let-7e, and binding of let-7e to at least one site within the cyclin d1 3'-utr may be sufficient to reduce cyclin d1 protein levels. 21258769_1 a luciferase reporter assay showed a significantly decreased signal at two mir-145 targetsites at the 3'utr of fscn1, suggesting that mir-145 directly regulates fscn1. 21258769_2 the expression level of fscn1 mrna was significantly decreased by mir-145 transfection in both pc cell lines . 21258769_3 the protein expression level of fscn1 was also markedly reduced in the pc cell lines after mir-145 transfection . 21258769_4 the luciferase reporter assay confirmed that the 3'utr of fscn1 contained actual target of mir-145. in summary, our expression profiles in pc cell lines show that fscn1 can have an oncogenic function and that mir-145 can act as a tumor suppressor through the direct control of fscn1 expression. 21785411_1 we prepared three reporter vectors targeted by mir-29: am147 3- utr, which has seven repeats of mir-29 sponge and can be regulated by mir-29 efficiently; http 3- utr, a target of mir-29 that has been reported before35; and ifn-gamma 3- utr, the predicted target of mir-29 that we verified above. 21785411_2 we cotransfected peritoneal macrophages from gs29 mice and their littermates by nucleofection with a renilla luciferase expression plasmid, a firefly reporter luciferase expression plasmid containing am147 3- utr, http 3- utr or ifn-gamma 3- utr. the luciferase activity of all three reporter vectors was upregulated in macrophages from gs29 mice. 21785411_3 however, when we mutated the mir-29-binding sites in the http 3- utr vector or ifn-gamma 3- utr vector, the upregulation of luciferase activity in gs29 macrophages was abolished accordingly. 21785411_4 in addition, we observed no substantial upregulation of the luciferase activity of a control 3- utr il-10 reporter vector in gs29 macrophages, consistent with the lack of mir-29-binding sites in the 3- utr of il-10 mrna . 21785411_5 once activated in vitro, nk cells, unpolarized helper t cells, helper t cells polarized in th1 conditions and cd8+ t cells isolated from gs29 mice produced more ifn-gamma than did those from control mice . 21987723_1 expression of c-ets-1 was regulated by mir-200 at both the mrna and protein level . 21987723_2 activity of a luciferase reporter containing the 3'-utr for c-ets-1 was directly regulated by co-transfection of mir-200b and c, but not mir-200a, as predicted from the seed sequence sites found in the 3'-utr . 24944696_1 fgfr3 is a direct target gene of mir-99a in bladder cancer. 24944696_2 fgfr3 mrna contained an mir-99a seven-nucleotide seed match at position 537-544 of the fgfr3 3'-utr. 24944696_3 fgfr3 may be a direct target of mir-99a in vitro. 25663460_1 in addition, mir-342-3p repressed rap2b expression through interactions with its 3'-utr region. 25663460_2 restoration of rap2b expression reversed mir-342-3p-mediated inhibitory activity in nsclc cells. 25663460_3 finally, analyses of mir-342-3p and rap2b levels in nsclcs revealed that mir-342-3p inversely correlated with rap2b mrna expression. 25663460_4 our collective findings provide preliminary evidence that mir-342-3p acts as a tumor suppressor in nsclc through repression of rap2b. 25663460_5 based on these findings, we propose that mir-342-3p inhibits rap2b expression by binding to its 3'-utr region. 25663460_6 these results suggest that rap2b is a functional target of mir-342-3p. 22102694_1 taken together, our study shows that tumor-suppressive mir-34a and mir-34c act as ulbp2 repressors. in summary, these results suggested that specific mir-34 and mir-449 family members are involved in the control of ulbp2 expression by binding to the 3'utr of its mrna. 22102694_2 this downregulation was associated with a reduction in ulbp2 mrna levels, suggesting that transfected mir-34a and mir-34c mimics induced degradation of the specific mrna, though an impact on translation could not be excluded . 22102694_3 the strongest inhibitory effect on targetexpression was exerted by mir-34c, as already observed in reporter gene assays . in summary, these data clearly showed the functional significance of ulbp2 downregulation by mir-34. 26548909_1 we found that pten was significantly down-regulated in mir-141-3p mimics group and up-regulated in mir-141-3p inhibitor group . 26548909_2 besides, the pten mrna expression in the mice was also detected, as shown in fig. 26548909_3 5c, the pten mrna expression level was significantly decreased in the hfd mice. 26548909_4 pten was the target of the mitochondria-related mir-141-3p. 26378023_5 and gpa genes were constructed into pgl3 luc vectors and the constructs were co-transfected with mir-23a, mir27-a or mir-24 into hek293t cells for 48 h. 26692091_2 our results show that mir-214 mediates iso-induced proliferation and collagen synthesis in cfs by directly targeting mfn2 and activating the downstream extracellular signal-regulated kinase-mitogen-activated protein kinase signalling pathway. 26692091_3 the outcomes showed that the mrna level of mfn2 was not affected, but the protein level was correspondingly decreased or increased when mir-214 was overexpressed or downregulated , indicating that mir-214 negatively regulates mfn2 expression by translational inhibition. in our study, mfn2 was found to decrease in fibrotic rat heart tissues and fibroblasts and was negatively regulated by mir-214. 26276722_1 therefore, mir-133b/a-3p directly targets and inhibits mcl-1 and bcl-xl translation. . 26276722_2 co-transfection of mir-133b/a-3p mimics significantly inhibited the luciferase activity of the mcl-1 and bclxl 3'-utr reporter but did not affect the luciferase activity of either a mcl-1 or a bcl-xl reporter with mutated mir-133b/a-3p binding sites 20133835_1 let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator tlx and the cell cycle regulator cyclin d1. 20133835_2 introducing an expression vector of tlx or cyclin d1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both tlx and cyclin d1 are important target for let-7b-mediated regulation of neural stem cell proliferation. 20133835_4 cyclin d1 mrna and protein levels were both reduced in the wild type let-7b-transfected cells , indicating that let-7b down-regulates cyclin d1 expression in neural stem cells. 24919189_1 cd44 has been shown to be a potential target of mir-328 in human cells, but the mir-328-targeting sequences found in 3'-utr of human cd44 do not exist in 3'-utr of rat cd44. 24919189_3 the highly complementary sequence of mir-328 in cd44 3'-utr is a target of mir-328 and essential for mir-328 repression of cd44 expression. 22475310_2 loss of mir17 family expression and concomitant increases in the mir17 target bim occurred in an additional all cell line sup-b15 but not in the dexamethasone-resistant reh 18930031_1 here, we show that mir-302b indirectly regulates expression of the pluripotent stem cell marker oct4, and it directly regulates expression of cyclin d2 protein, a developmental regulator during gastrulation. 18930031_2 our results suggest that mir-302b plays an important role in maintaining the pluripotency of eccs and probably escs, by post-transcriptional regulation of cyclin d2 expression. 18930031_3 these data indicate that there is a strong possibility that cyclin d2 is a target of mir-302b post-transcriptional regulation and this possibility would be consistent with the reciprocal down-regulation of cyclin d2 protein. 22198213_1 here, we identified fra-1 as a new target of mir-34a and demonstrated that mir-34a inhibits fra-1 expression at both protein and messenger rna levels. 22198213_2 cotransfection experiments showed that mir-34a decreased the luciferase activity of luc-fra-1 3'-utr but had a minimal effect on luc-fra-1-mut 3'-utr , indicating that fra-1 is a potential target of mir-34a. 22198213_3 western blotting analysis showed that transfection of mir-34a resulted in significant reduction of fra-1 protein , and real-time rt-pcr analysis indicated that fra-1 mrna levels were also reduced, though to a less extent . 22198213_5 taken together, these data suggest that the effects of mir-34a on cell migration and cell invasion are in part mediated by fra-1. 26612257_1 mir-543 inhibits sirt1 expression by targeting its 3'-utr. 22709905_1 we found that tumor necrosis factor-receptor-associated factor 3 traf3 is a direct targetfor mir-32, and overexpression of mir-32 in chme3 cells decreased traf3 both at the mrna and the protein level. 22709905_2 thus, our results suggest a novel mirna mediated mechanism for regulation of traf3 in human microglial cells exposed to hiv-1 tat c protein. 22709905_3 traf3 protein level decreased sharply with the increase in tat-c mediated upregulation of mir-32 , suggesting that traf3 can be a direct target of mir-32 and that its expression can be modulated by changes in mir-32 expression. 23834154_1 mir-21 downregulation also caused increased programmed cell death and a decrease in the expression levels of bcl-2 protein, although parp cleavage was not affected, indicating that apoptosis was not the relevant mechanism underlying the observed results. 23834154_2 treatment with antimir-21 caused an increase in the autophagy related proteins beclin-1, vps34 and lc3-ii. 26550150_1 these results suggest that bcl-2 is a key regulator for mir-192 related resistance for gemcitabine and cisplatin combined chemotherapy. 26550150_2 bcl-2 mrna level was over-expressed in mir-192-suppressed tumor compared with controls . 26550150_4 these suggest that bcl-2 is a target of mir-192. 26389681_1 finally found that only the protein level of stat3 could be decreased by mir-125a, which indicated that stat3 was the target gene of mir-125a. 26389681_2 the top panel indicates wild-type and mutant forms of putative mir-125a target sequences in the stat3 3'-utr. 26389681_3 taken together, these results indicate that mir-125a inhibits stat3 expression by directly binding its 3'-utr in cc cells. 24796455_1 flow cytometry indicated that the apoptotic index was % in the mir-224 aso group and % in the control group . in addition, the expressions of bcl2 mrna and protein were 1.05-0.04 21690378_1 mir-155 overexpression in pb cd14+ cells markedly decreased ship-1 mrna expression, whereas inhibition of mir-155 significantly increased the expression of ship-1 mrna in ra sf cd14+ cells . 21690378_2 to verify that human ship-1 is targeted directly by mir-155, the 3- utr of ship-1 was cloned into a pmir luciferase system. 21690378_3 these results demonstrate that mir-155 can directly target human ship-1 for degradation. 26318567_1 a successful transfection of let-7a-2-3p/let-7b-3p into hbe and a549 cells,the k-ras expression was up-regulated in radon-treated hbe cells, and was down-regulated in let-7a-2-3p and let-7b-3p over-expressed hr-5 and hr-10 cells. 26318567_2 by applying informatics analysis, hsa-let-7b-3p was predicted to target the 3'utr of k-ras gene at the position of 4382 . 26318567_3 the k-ras expression was down-regulated by over-expression of let-7b-3p, and was up-regulated as a result of either inhibition of let-7b-3p or cotransfection with let-7b-3p inhibitor. 26318567_4 a negative correlation was established between the expression of let-7b-3p and k-ras. 23189820_2 furthermore, global analyses of atl patient samples have provided a conceptual progress that polycomb family induces mir-31 silencing, resulting in overexpression of nf-kappab inducing kinase following nf-kappab activation. 25215905_1 moreover, mir-193b inhibited the expression of stathmin 1 and urokinase-type plasminogen activator in panc-1 cells. 25215905_2 mir-193b directly represses the expression of stmn1 and upa through binding to their 3'-utrs. 25215905_3 these results indicated that stmn1 and upa are the direct downstream targets of mir-193b in pancreatic cancer. 25215905_4 these data suggest that stmn1 and upa expression is negatively regulated by mir-193b. 20444294_1 the targetsequence of mir-101 located in the 3' utr of both ezh2 and eed's mrna was identified by bioinformatic analysis and was validated by reporter luciferase reporter assay. 20444294_3 fig.3c,3c, when the luciferase gene carried 3' utr region of either ezh2 or eed's transcript, the luciferase activity was inhibited by over-expressing mir-101-1 or mir-101-2 but not by the control mir-lacz. 20622856_1 these results indicate that mir-134 regulates creb protein expression via a post-transcriptional mechanism. 20622856_2 these results indicate that mir-134 attenuates creb expression via a specific interaction with the target regions within the 3'utr of creb. the expression of mir-34b-5p or mir-34c,two other mirnas upregulated in brains of sirt1d mice,had no effect on creb activity , indicating specific regulation of creb by mir-134. 20622856_3 comparative genomic analyses of the 3' untranslated region of the mouse creb gene revealed three partial complementary binding sites for mir-134, with one site being well-conserved . 20622856_4 these results suggest that mir-134 regulate creb protein expression via a post-transcriptional mechanism. 25310480_1 following a preliminary screen, the mir-214 binding site located on the 3'-utr of pten was found to be conserved in different species . 25310480_2 furthermore, a previous study reported that mir-214 suppresses pten expression in human ovarian tumor cells. 25310480_3 the western blot analysis demonstrated that transfection with mir-214 mimics reduced the pten protein expression levels in saos-2 cells. 25310480_4 furthermore, mir-214 overexpression was found to increase the protein levels of p-akt . 25310480_5 these results suggest that pten is a target of mir-214 in os cells. 26620225_2 we found that mir-631 can bind to the 3'-utr of zap70 and decrease its expression. 26620225_3 interestingly, using gain- and loss-of function experiments, we found that zap70 is a major target of mir-631 and largely mediates its activity. 26620225_4 in addition, we further discovered that mir-631 was downregulated and zap70 was overexpressed in pca cell lines and pca tissues. 26620225_5 a concordant inverse correlation between mir-631 and zap70 was also found in pca tissues. 26620225_6 fig. 2. zap70 is a target of mir-631. 26620225_7 collectively, the data indicated that mir-631 can negatively regulate zap70 expression by directly binding to its 3'-utr. 26620225_8 fig. 4. mir-631 inhibits cell migration and invasion through zap70. 25268950_1 overexpression of mir-34a significantly suppressed migration and invasion in tscc cells and simultaneously inhibited the expression of mmp9 and mmp14 through targeting the coding region and the 3' untranslated region, respectively. 25268950_2 mir-34a plays an important role in lymph node metastases of tscc through targeting mmp9 and mmp14 and may have potential applications in prognosis prediction and gene therapy for lymph node metastases of tscc patients. 25268950_3 mechanistic analysis showed that mir-34a inhibited migration and invasion of tscc cell lines via targeting the coding region of mmp9 and the 3' untranslated region of mmp14. 25268950_4 these results suggested that mmp9 and mmp14 could be direct targets of mir-34a. 23460283_1 both mir-27a and -29a targetsp1, and mir-133a target cdc42. 23460283_3 thus, the beneficial effect of neb over atn could be explained by upregulation of mir- 29a and -27a, with subsequent suppression of sp1. 23460283_4 we are also showing that in vitro overexpression of mir-27a and -29a attenuated ang induced upregulation of sp1 levels and collagen in cardiac myofibroblasts. 23460283_5 thus, the beneficial effect of neb over atn could be explained by upregulation of mir-29a and -27a, with subsequent suppression of sp1. 19033458_1 here we demonstrate not only that the lipid phosphatase ship2 is a target of mirna-205 in epithelial cells, but, more importantly, that the corneal epithelial-specific mir-184 can interfere with the ability of mir-205 to suppress ship2 levels. 19033458_3 interfering with mir-205 function by using a synthetic antagomir, or by the ectopic expression of mir-184, leads to a coordinated damping of the akt signaling pathway via ship2 induction. 19033458_7 partial knockdown of endogenous mir-205 in sccs markedly decreased phosphorylated akt and phosphorylated bad levels and increased apoptosis. 19033458_8 we were able to increase ship2 levels in scc cells after inhibition of mir-205. 19033458_10 blockage of mir-205 activity with an antagomir or via ectopic expression of mir-184 could be novel therapeutic approaches for treating aggressive sccs. 22609116_1 pik3r1 , a negative regulator of the phosphatidylinositol 3-kinase -akt pathway,was identified as a direct target of mir-155. 22609116_2 a luciferase reporter was repressed through the direct interaction of mir-155 and the p85alpha 3'-untranslated region, and overexpression of mir-155 down-regulated both the transcription and translation of p8alpha . 22609116_3 knockdown of mir-155 down-regulated akt activity, presumably at least partially by releasing the repressing effect on p85alpha . 22609116_4 mir-155 activates the pi3k-akt signaling pathway by targeting p85alpha. 21636785_1 mir-21 negatively regulates pparalpha expression by targeting its 3'-utr. 21636785_2 oss induction of mir-21 represses pparalpha through direct targeting at its 3'-utrs. 21636785_3 these data indicate that mir-21 can regulate pparalpha level by targeting its 3'-utrs. 21636785_5 2.mir-21 target 3'-utrs of pparalpha to regulate its expression and activation. 21636785_6 the two conserved mir-21 binding sites locate in 3'-utrs of ppara. 21636785_7 these results indicate that mir-21 regulates pparalpha expression by inhibiting the translation, but not destabilization, of its mrna. 21636785_8 these results indicate that pparalpha negatively regulates mir-21 transcription, which is mediated by ap-1. 26006243_1 furthermore, we delineated that mir-24 regulates post-transcriptionals of t-cell factor-1 via targeting the 3'-untranslated region of tcf-1 mrna. 26006243_2 we demonstrate here that mir-24 regulates osteogenic differentiation through targeting and regulating the expression of tcf-1. 26006243_3 the direct interaction between mir-24 and tcf-1 was detected by a dual luciferase reporter assay, which was further validated in a gain- or loss-of-function study in bmscs and mc3t3-e1 cells. 26494558_1 all these results showed that bcl-2, mcl-1 and xiap were the target genes of mir-130a .bcl-2, 22454525_1 these results indicate that mir-378a-5p target nodal 3'utr to repress its expression. 22454525_2 microrna-378a-5p promotes trophoblast cell survival, migration and invasion by targeting nodal. 22454525_3 using in silico analysis, mutagenesis, luciferase reporter assays, and western blot analyses, we showed that mir-378a-5p interacts with a partially complementary sequence on the nodal 3'utr to inhibit its expression. 17007876_1 we used microarrays to identify putative targets for the two srnas and found that induction of rybb strongly down-regulated ompc and ompw .the 17007876_2 effect of rybb expression on ompc and ompw mrna levels was confirmed by northern blot analysis.consistent 17007876_3 with the microarrays, however, the effect of rybb was stronger on the ompc mrna than on the ompw mrna. 26255816_2 this result suggests that mir-378a-3p regulates golt1a expression by binding to the 3'-utr of golt1a. 26255816_3 luciferase reporter assay using the 3'-utr region of golt1a gene including a putative binding site for mir-378a-3p suggested that mir-378a-3p could decrease golt1a mrna expression. 22160209_1 furthermore, mir-143 suppressed the activity of a luciferase reporter carrying the 3'-utr of bcl-2, which was abolished by mutation of the predicted mir-143-binding site, indicating that bcl-2 is a mir-143 target gene. 22160209_2 our study revealed a molecular link between mir-143 and bcl-2. 22160209_3 direct involvement in the regulation of bcl-2 may be one of the mechanisms through which mir-143 may play a role in the pathogenesis of cervical cancer. 26370665_1 we chose to use the eec cells that are representative of eecs for the 3'utr analyses to study that mir-451 can directly target the ywhaz mrna transcript. 26370665_2 the down-regulation of mir-451 was associated with an increase in ywhaz 26221296_2 bioinformatics analysis and luciferase assays demonstrated mir-h4b can directly target p16 mrna. 26221296_5 mir-h4b inhibits pi3k-akt and mtor pathways by targeting p16. 23528537_1 taken together, these results suggest that mir-130a is involved in regulating hoxa5 expression in response to ra treatment. 23528537_2 in consistent with this notion, we show that mir-130a posttranscriptionally regulates the cellular levels of hoxa5. 23528537_3 intriguingly, mir-130a itself is controlled by the oncoprotein c-myc. in summary, the findings presented here suggest the existence of the dynamic regulation of hoxa5 expression by hur and mir-130a in response to ra treatment, and implicate the importance of hur and mir-130a in the regulation of ra-induced cell death. 23445407_3 these results suggest that mir-30a is specifically targeting the 3'-utr regions of foxd1 and aven. 23445407_5 however, a potential compensatory effect by other members of the mir-30 family may explain the lack of effect after efficient downregulation of mir-30a. 24528955_1 further investigation revealed that both the pro-apoptotic factor genes bak1 and bmf and the anti-apoptotic factor gene bcl-w are targets of mir-29a 26097565_1 phosphatase and tensin homolog was identified as a direct target of mir-106a, and over-expression of mir-106a suppressed pten by direct binding to its 3'-untranslated region . 26097565_2 furthermore, the presence of mir-106a was inversely correlated with pten in nsclc tissues. 26097565_3 overall, this study suggested that mir-106a inhibited the growth and metastasis of nsclc cells by decreasing pten expression. 26097565_4 these data further indicated that pten was a target of mir-106a in nsclc. 26031775_1 furthermore, the mir-16 binding sequence in the feat 3'-utr is highly conserved across species. 26031775_2 combining the computational prediction with the detection of inverse correlation between mir-16 and feat in vivo, it is quite likely that mir-16 is involved in the post-transcriptional regulation of feat. 26031775_3 these results demonstrate that mir-16 specifically regulates feat protein expression at the post-transcriptional level, which is a typical mirna-mediated regulation mechanism. 23630078_2 the gene nr6a1, also known as germ cell nuclear factor , was notable among "high-confidence" let-7 targets, since it meets the criteria of a classical developmental target of let-7. 23630078_3 we also demonstrated its interaction with the risc at predicted let-7 target sites , indicating that nr6a1 is a direct target of let-7. 23630078_4 finally, nr6a1 is part of the mid-gestation signature regulated by let-7, with a peak in expression around e8.5 and a subsequent decrease anti-correlating with let-7 in the whole mouse embryo and in the mouse embryonic limb bud . in total, we identified nr6a1 as a let-7 target that mediates secondary transcriptional gene expression changes in dicer knockout mscs. 22359598_1 mir-214 directly target xbp-1 by interaction with the 3'-utr. 22359598_3 these results suggest that mir-214 target xbp-1 by directly binding the 3- utr of xbp-1. 23296900_1 these data provide further evidence that pdcd4 was negatively correlated with mir-182. 23296900_2 these data highlight the direct regulation of pdcd4 by mir-182. 23296900_3 therefore, we suggested that mir-182 reduces sensitivity of ovarian cancer cells to cddp and taxol via suppression pdcd4 expression. 23296900_4 collectively, we found that mir-182 directly and negatively regulates tumor suppressor pdcd4 and enhances multiple malignant phenotypes in ovarian cancer cells. 23296900_5 using fluorescent reporter assay, we confirmed the direct and negative regulation of pdcd4 by mir-182, which was dependent on the predicted mir-182 binding site within pdcd4 3' untranslated region . 26064239_1 mir-374a directly targets foxo1 by binding to its 3'-utr in os 21715310_1 luciferase assays were used to confirm the predicted interaction of mir-221 with the 3'-utr of ets2. 21715310_2 mir-221 repressed a construct containing the ets2 3'-utr downstream of the luciferase gene . 21715310_4 in addition, 2 putative mir-222-binding sites were mapped in the 3'-utr of ets1 . 21715310_5 reporter assays again showed that mir-222 could directly interact with both binding motifs and reduce the activity of a luciferase reporter gene fused to the ets1 3'-utr . 21715310_6 mutating either of the predicted mir-222-binding sites restored mir-222-mediated repression . 23318130_1 mirna-124a mimic induced a decrease in luciferase activity, which could be reversed by simultaneous administration of the respective anti-mirna, indicating that mecp2 is a direct target of mirna-124a as predicted . in spinal cord slices, we could show that mecp2 protein is localized in the same cells in which mirna-124a is expressed , thus indicating their possible interaction. 23318130_2 down-regulation of mirna-124a in the spinal cord after formalin injection into the hind paw was associated with significantly increased mecp2 mrna expression at 2 hours after oligonucleotide injection . 21989846_1 sox6 is a novel target of mir-155 and that mir-155 enhances liver cell tumorigenesis. 21989846_2 these results indicated that mir-155 suppressed sox6 expression not only by blocking translational processes but also by inducing sox6 mrna cleavage directly, and the former was dominant. 21989846_3 having established sox6 as a targetfor mir-155, its expression levels in primary hcc tissues were assayed. 21989846_5 higher sox6 levels were observed when mir-155 expression levels were reduced, irrespective of the tumor status of the tissue. 21989846_6 in conclusion, the current study has revealed a novel mechanism involving the regulation of sox6 and p21 by mir-155, and we postulate that this mechanism is a key step in the multistep process leading to the development of hcc. 22234835_1 these results indicate that pik3cd mrna is a specific target of mir-7 and demonstrate that the mir-7 targetsites a, b, and c are major sites for interaction with mir-7. 22234835_2 ectopic expression of mir-7 was elevated by approximately 7-fold , which resulted in a 0.24-fold reduction of pik3cd mrna . 22234835_3 these results indicate that mir-7 participates in the regulation of cell proliferation and migration by directly regulating pik3cd expression. 22234835_4 these data indicate that mir-7 can regulate the expression of mtor, p70s6k, and pik3cd by directly binding to targetsites within the 3'utr, supporting our conclusion that mir-7 can inhibit hcc cell proliferation and movement by regulating the pi3k/akt/mtor-signaling pathway. 22234835_5 these data indicate that overexpression of mir-7 may inhibit hcc tumorigenesis by blocking pik3cd expression. 20190740_1 to identify the mir-19 targets responsible for its oncogenic action, we conducted a large-scale short hairpin rna screen for genes whose knockdown can phenocopy mir-19. 20190740_2 strikingly, the results of this screen were enriched for mir-19 target genes, and include bim , amp-activated kinase and the phosphatases pten and pp2a . 23759586_4 use of antisense mir-125b transcripts enhanced expression of pro-apoptotic p53, repressed expression of anti-apoptotic sirt1 and, importantly, significantly enhanced dexamethasone-induced cell death responses in mm. 21671467_1 mir-338-3p targeting the smo gene. 21671467_2 mir-338-3p reduced smo 3'-utr luciferase activity compared with the control. 21671467_3 furthermore, mir-338-3p did not have any observable effects on the mutated smo 3'-utr luciferase reporter , indicating that mir-338-3p indeed was able to silence smo gene expression. 21671467_4 these results suggest that the effects of mir-338-3p are through suppression of smo expression. in conclusion, our study demonstrated that mir-338-3p can inhibit liver cancer cell invasion through inhibiting smo-mediated mmp9 expression in vitro. 26886608_1 therefore, mir-17-92 negatively regulates the expression of bim, stat3, c-kit, and socs3 in mouse testes. 26886608_2 more importantly, these aforementioned results suggest that bim, stat3, c-kit, and socs3 are direct targets of the members of mir-17-92 cluster. 19666866_2 functional analysis of chl cell lines showed that mature mir-135a levels increased following pre-mir-135a transfection, causing apoptosis and decreased cell growth. 19666866_3 target analysis showed a direct regulation by mir-135a of jak2, a cytoplasmic tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. 19666866_4 mir-135a-mediated jak2 downregulation led to decreased mrna and protein levels of the antiapoptotic gene bcl-xl, suggesting a role for bcl-xl in mir-135a/jak2-mediated apoptosis. 19666866_5 our findings confirm the critical role of mir-135a in the survival of chl cells and in the prognosis of chl patients, indicating that novel treatment approaches targeting mir-135a may potentially benefit these patients. 18803879_1 for mir-34 restoration, we transfected the kato iii cells with mir-34 mimics. 18803879_2 as shown in figure 3, western blot analysis revealed that transfection of mir-34 mimics downregulated targetgene bcl-2 expression at the protein level, but had no obvious effect on bcl-xl and mcl-1 expression, indicating that the bcl-2 knockdown by mir-34 mimics was sequence-specific. 18803879_3 as a target of mir-34, bax was also downregulated by mir-34. 23637592_1 we identified a novel mir-155 target, det1, an evolutionarily-conserved factor involved in c-jun ubiquitination. 23637592_2 these results suggest that det1 protein translation is directly targeted by mir-155 binding to the 3' utr sequence. 23637592_3 together, these experiments show that mir-155 can target det1 leading to c-jun accumulation in transformed theileria-infected leukocytes. 23637592_4 we provide evidence that mir-155 targets the det1 protein, which leads to accumulation of the c-jun protein and increased transcription of the mir-155-encoding bic gene . 22438124_2 furthermore, cellular mechanism studies revealed that induction of mir-34a decreased the expression of notch-1 and its downstream targets including hes-1, cyclin d1, survivin and bcl-2. 23484856_1 we find that mir-125a-5p targets evolutionarily conserved sequences in the lfng 3' utr and that preventing interactions between mir-125a-5p and lfng transcripts in vivo causes abnormal segmentation and perturbs clock activity. 23484856_2 mutation of predicted mir-125a-5p binding sites at either end of the mouse 3' utr, or of the single site in the chicken 3' utr abrogates the effect of exogenous mir-125a-5p, indicating that mir-125a-5p directly interacts with the lfng 3' utr and that these interactions are conserved among organisms that utilize lfng in the segmentation clock. 23484856_3 overall, our findings are consistent with a model wherein blocking interactions between mir-125a-5p and lfng in chick embryos initially results in stabilization of lfng mrna, although we cannot rule out that this interaction may also affect translational efficiency of the transcripts . 20735984_2 these results indicated that mir-155 interfered with luciferase mrna translation via direct interaction with rat at1r 3'-utr. 20735984_3 however, western blot assay revealed significantly reduced at1r protein expression in afs transfected with psuper/mir-155 compared with controls . 26172280_1 interestingly, mir-484 was previously found to be significantly downregulated in intercept platelets , and its positive correlation with abhd16a mrna that is also downregulated in intercept platelets may suggest a regulatory role of mir-484 for this gene. 26172280_4 a complete network of all identified mirna-mrna interaction pairs is shown in fig 7. this network shows mirnas associated with the most significantly downregulated mrnas in intercept platelets. 26460733_1 twist1 was predicted as a potential target gene of mir-129-5p based on mir-target analysis,the predicted binding of mir-129-5p with the twist1 3'-utr. 26460733_2 twist1 protein expression increased when mcf7 cells were treated with mir-129-5p inhibitor and decreased when mda-mb-231 cells were treated with mir-129-5p mimic. 26460733_3 luciferase activity was significantly increased in mir-129-5p depleted mcf7 cells , whereas it was decreased in mir-129-5p over-expressing mda-mb-231 cells compared with controls. 21304530_1 mir-1 and mir-133a showed potential role of tumour suppressors by functional analyses of bc cells such as cell proliferation, apoptosis, migration, and invasion assays. 21304530_2 molecular target searches of these mirnas showed that transgelin 2 was directly regulated by both mir-1 and mir-133a. 26075749_1 based on bioinformatic analysis, the sequence of mature hsa-mir-708-5p matches the 3- -untranslated region of nnat mrna. 26075749_2 the result showed that mir-708-5p significantly suppressed the expression of nnat in prostate cancer cells . 26075749_4 mir-708-5p showed a significant suppressive effect on the firefly luciferase activity compared with mir-nc and mock control . 26075749_5 because nnat expression is responsible for the uptake of calcium by the er, we tested if mir-708-5p- and metformin-induced knockdown of nnat changed the level of calcium in the cytoplasm and the reuptake to er. these results imply that metformin and mir-708-5p induce apoptosis and er stress in prostate cancer cells by targeting nnat. 23053883_1 in comparison to the controls, a significant increase in the expression of mir-451 was associated with significantly decreased expressions of bcl-2, akt and p-akt, and a significant increase in the apoptosis rate. 18663355_1 analysis of paired normal/tumor tissues from additional 10 patients revealed an increase in mir-196a in the cancers , accompanied by a decrease in anxa1 mrna . 18663355_2 increasing mir-196a levels in cells by mir-196a mimics resulted in decreased anxa1 mrna and protein. in addition, mir-196a mimics inhibited luciferase expression in luciferase plasmid reporter that included predicted mir-196a recognition sequence from anxa1 3'-untranslated region confirming that mir-196a directly targets anxa1. 18663355_4 this study demonstrated a novel mechanism of post-transcriptional regulation of anxa1 expression and identified mir-196a as a marker of esophageal cancer. 26147452_1 we show that microrna-194 expression is uniquely suppressed in ebv+ b cell lines from ptld patients and that the 3'untranslated region of il-10 is targeted by microrna-194. 26147452_2 overexpression of microrna-194 attenuates il-10 production and increases apoptosis of ebv+ b cell lymphoma lines. in contrast, a vector expressing mir-340, which is modulated by ebv but is not predicted to target the 3'utr of il-10, had no effect on renilla luciferase expression . 26875774_1 furthermore, we demonstrated that the expression of the foxp3 gene was modulated by mir-125a-5p in jurkat cells. 26875774_2 therefore, we concluded that the inserted fragment of the foxp3 3'-utr was the target of mir-125a-5p. 26875774_3 thus, it is likely that mir-125a-5p decreases foxp3 expression by targeting its mrna for degradation. 26875774_4 next, we obtained direct evidence that foxp3 is a target of mir-125a-5p using a luciferase reporter assay. 26510977_1 our study provides a better understanding of the regulatory capacity of mir-211 in promoting ganglion cell dysplasia by targeting the expression of gdnf. 26510977_2 these results suggested that mir-211 regulated the expression of gdnf in the rgc-5 cells. 22362515_1 validation experiments identified ncx1 as a novel functional mir-1 target within the 3- utr of ratncx1 gene, we identified a putative mir-1-binding sequence that is highly conserved throughout evolution . 22362515_2 mir-1 overexpression in cultured cardiomyocytes silenced ncx1 protein expression . 22362515_3 indeed, luciferase activity was decreased by more than 60% when mir-1 was overexpressed, confirming the direct targeting of ncx1 by mir-1 . 20560046_2 programmed cell death 4 , phosphatase and tensin homology deleted from chromosome 10 , sprouty1 , and sprouty2 are the current identified target genes of mir-21 that are involved in mir-21-mediated cardiovascular effects. 16859494_1 sgrs is an hfq-binding small antisense rna that is induced upon phosphosugar stress. 16859494_2 it forms a ribonucleoprotein complex with rnase e through hfq to mediate silencing of the target ptsg mrna encoding the membrane component of the glucose-specific phosphoenolpyruvate phosphotransferase system.specific 16859494_3 single nucleotide substitutions around the shine-dalgarno sequence of ptsg completely eliminated sgrs action while compensatory mutations in sgrs restored it. 16859494_4 a systematic mutational analysis of both ptsg and sgrs rnas revealed that six base pairs around sd sequence of ptsg are particularly important for sgrs action. 23211491_2 they also suggested that mir-98 could reduce cell adhesion, cell proliferation, cell survival and endothelial cell activities through the down regulation of alk4. 23211491_3 they also suggest that mir-98 could reduce cell invasion, endothelial tube formation and cell survival through down-regulation of mmp11. 23211491_4 these results suggested that mir-98 played an important role in regulating mmp11 effects in 4t1 cells. 22287707_1 to investigate the potential involvement of c-myb in mir-150 mediated inkt cell regulation, we first evaluated c-myb expression in thymus immature and mature inkt cells by a taqman real-time rt-pcr. 22287707_4 thus, during inkt cell development in thymus, the dynamic expression pattern of c-myb is in mirror contrast with that of mir-150 , which may be required for inkt cell maturation. 22287707_5 furthermore, c-myb expression was significantly upregulated in both immature and mature inkt cells from mir-150ko mice compared with that in wt mice . 22287707_6 thus, these data indicate that c-myb may serve as one of the potential targets in mir-150-mediated late-stage inkt cell development defect in the thymus. 23968872_1 transfection of a mimic of mirna-30b led to decreases in alkaline phosphatase activity and expressions of runx2, smad1, and caspase-3. 23968872_2 furthermore, dual luciferase reporter assays confirmed that runx2, smad1, and caspase-3 are direct targets of mirna-30b. 22660319_1 therefore, an age-related increase in let-7 is one mechanism by which imp expression could be regulated in an ageing-dependent manner in testes from older males. 22660319_2 these data confirm that let-7 can destabilize imp through sequences in the 3' utr . 22660319_3 however, further increasing the levels of let-7 resulted in a decrease in gfp expression from the mutated 3' utr, indicating that other, putative let-7 seeds in the imp 3' utr can be targeted by let-7 . 26306811_1 using an online microrna target database wefound rock1 as the putative target of mir-146a withcomplementary 3'-utr sites for the seed sequence ofmir-146a. 26306811_2 the resultssuggested that mir-146a targeted rock1 directly andconsequently actived caspase3 protein which exerted acritical role in cell apoptosis. 26447227_1 these data are consistent with an important role for ship1 downstream of mir-155 in regulating the ability of the dc to induce a functional immune response. 26447227_2 these data support an important role for ship1 as a critical target downstream of mir-155 in regulating dc function. 26447227_3 rather, our study has supported a role for ship1 in regulating dc function downstream of mir-155. 19342891_1 mir-302 reduces p63 protein and mrna levels through two targetsites within the p63 3' untranslated region. 19342891_2 interestingly, analysis by quantitative rt-pcr revealed that mir-302b was also capable of reducing the amount of p63 mrna , suggesting that it suppresses gene expression through mrna degradation. 26354756_1 in cd4 and cd8 t cells in aplastic anemia patients, myc and pik3r2 were up-regulated and proved to be targets of mir-145-5p and mir-126-3p, respectively. 18755897_1 mir-34 inhibition of sirt1 leads to an increase in acetylated p53 and expression of p21 and puma, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. 26858253_1 in contrast, ifngamma increased pro-apoptotic txnip post-transcriptionally via induction of endoplasmic reticulum stress, activation of inositol-requiring enzyme 1alpha and suppression of mir-17, a microrna that targets and downregulates txnip. 26858253_2 most importantly, overexpression of mir-17 was able to blunt ifn纬-induced txnip expression , suggesting that ifngamma up-regulated txnip expression via inhibition of mir-17. 26858253_3 combined, these findings suggest that ifngamma induces txnip expression via induction of er stress, activation of ire1alpha and degradation of mir-17. 22805767_1 by real-time pcr, western blot analysis and mirna mimic and 3'-utr-luctransfection, we found that trim68 is a direct target of mir-29a and mir-1256 and that the downregulation of mir-29a and mir-1256 in pca cells leads to increased expression of trim68 and pgk-1 in pca cells and in human tumor tissue specimens. 22805767_2 figure 3. targeting trim68 by mir-29a and mir-1256. 22805767_3 computerized analysis showed mir-29a and mir-1256 sequence alignment to the sequence of trim68 3'-utr. 22805767_4 furthermore, using real-time rt-pcr and western blot analysis, we observed that mir-29a or mir-1256 transfection inhibited the expression of trim68 mrna and protein , suggesting that trim68 is a target of both mir-29a and mir-1256. 26565914_1 via luciferase reporter assay, we confirmed lrp8 as a direct mir-130/301 target . 26565914_2 in cultured paafs, mir-130a decreased lrp8 expression, while inhibition of mir-130/301 increased lrp8 . 19859555_1 p27 inversely correlated with mir-221 and mir-222 expression, and indeed we show that p27 mrna is a direct target of these mirnas. 19859555_2 in contrast, when src was activated in myotubes, p27 protein levels were reduced up to 5 fold while p27 mrna levels were barely affected , suggesting that down-regulation of p27 protein involves translational inhibition mechanisms, possibly dependent on the corresponding increased accumulation of mir-221/222. 19859555_3 in both cell types, inhibition of mir-221/222 resulted in a partial recovery of p27 accumulation , suggesting that p27 mrna is regulated by these mirnas in myogenic cells. 21047769_1 mir-21 which targeted the 3' untranslated region of msh2 mrna and downregulated its expression. 21047769_2 we thereby speculated that tgf--beta downregulated msh2 by inducing mir-21-mediated posttranscriptional repression. 22660636_3 the sequences of the mature mmu-mir-196a and -196b are the same as those of the hsa mir-196a and -196b. 22660636_5 a schematic diagram of the mouse celf2 3'-utr indicating the locations of the authentic mir-196a and -196b targetsites that are conserved in vertebrates. 22660636_6 we found that celf2 mrna and protein levels were significantly reduced by treatment with mir-196a and mir-196b in hek293t cells and that celf2 was required for ar mrna stability . 22660636_7 on the basis of these findings, we concluded that mir-196a and mir-196b were able to decrease the expression levels of ar mrna and protein by silencing celf2, a protein that enhances the stability of ar mrna through direct binding to the cug triplet repeat sequence in exon 1 of the ar mrna. 26080425_1 here, we show that acquired trail resistance is mediated by a positive feedback loop involving the nf-kappab transcription factor, mir-21, mir-30c, and mir-100 and their respective targets caspase-8, caspase-3, forkhead box o3a , and tnf receptor-associated factor 7 . 26505221_1 systematic bioinformatics analyses suggested that foxo3 is a target gene of mir-223, and its 3'utr contains potential binding sites for mir-223. 26505221_2 one recent study reported that foxo3 is a target of mir-223 posttranscriptional repression . 26505221_3 western blot analyses demonstrated that mir-223 mimics significantly reduced the expression of foxo3 protein in macrophages. 26505221_4 the overexpression of mir-223 in human macrophages significantly reduced luciferase activity for the wild-type constructs,but no alterations in luciferase activity were detected with the mutant foxo3 3'-utr luciferase reporter plasmid .these 26505221_5 results indicated that mir-223 inhibited macrophage apoptosis through the direct downregulation of foxo3. 25846727_1 overexpression of mir-21 resulted in decreased expression of p85alpha in both miapaca-2 and hs766t . 25846727_2 pten expression decreased in response to mir-21 overexpression in hs766t but not miapaca-2 . 25846727_4 to test the functional effect of mir-21 overexpression, panc-1 cells treated with or without mir-21 mimic were tested for gemcitabine sensitivity. 25846727_5 overexpression of mir-21 led to gemcitabine resistance , the opposite effect of p85alpha overexpression . 26837315_1 furthermore, western blot assays showed that vegf-a was a potential target of mir-320a, which was verified by anti-ago2 co-immunoprecipitation. vegf-a is a target of mir-320a. 22223733_1 in this study, we present for the first time evidence that vegfr-3 can be negatively cd by a mirtron, hsa-mir- 1236 , which is expressed in primary human lymphatic endothelial cells. 25733534_1 it was also found that mir-125a-5p could negatively regulate e2f3 expression at posttranscriptional level, via a specific target site in the 3' untranslated region. 25733534_3 thus, our findings suggest that mir-125a-5p may act as a negative regulator of c2c12 myoblast proliferation by targeting e2f3. 26898440_1 mir-132 inhibited sirt1 and srebp-1c expression and downregulated their targeted genes, including hmgcr and fasn. 26898440_2 the results confirmed that mrnas of sirt1 were straight goals of mir-132. 26898440_3 mir-132 inhibited cholesterol biosynthesis and fatty acid via reduction of sirt1 and lipogenic or cholesterogenic transcription factors, srebp-1c, and their lower regulated genes, including hmgcr and fasn. 15829500_1 saf might regulate the expression of fas alternative splice forms through pre-mrna processing. 15829500_2 to study the potential regulation of the fas gene expression by the antisense saf, overexpression of saf was performed in jurkat cells. 25725129_1 mir-33b directly bound to hmga2 3' untranslated region to suppress its expression as measured by dual-luciferase assay. 25725129_2 thus, ef24 keeps the pro-metastatic gene hmga2 in check by targeting mir-33b. in consistent with western blotting results, immunofluorescence staining indicated that mir-33b knockdown or hmga2 overexpression reverted ef24-induced epithelial differentiation of melanoma cells . 25725129_3 these data implied that stress fiber formation and focal adhesion assembly were located in the downstream of hmga2 transcription which can be suppressed by ef24-upregulated mir-33b. 25678371_1 mir-148a targets bach2, mitf and proapoptotic factors such as pten and bim. the repression of the luciferase reporter by mir-148a was significantly abrogated in all three cases, indicating a direct binding of mir-148a to the 3 ' utr sequences of the respective mrna targets . 25678371_2 mir-148a targets plasma cell delaying gc transcription factors bach2 and mitf. 25678371_3 as mir-148a is the most abundant mirna in mature murine and human bm pcs , it could also play a pivotal role in maintaining the identity and life span of terminally differentiated pcs by preventing re-expression of bach2 or mitf and reducing the abundance of the proapoptotic proteins bim and pten. 22583478_1 a search for mir-16 target showed that the ccne1 gene, encoding the cell cycle regulator cyclin e, contains conserved putative mir-16 targetsites in its mrna 3' utr region. 22583478_2 targetgenes of mir-16 were searched through a bioinformatical approach, and the study was focused on cyclin e. reporter gene assays were performed to confirm that cyclin e 3'utr is a direct target of mir-16. 22583478_3 noticeably, although not responsive to the endogenous changes of mir-16 levels, a higher basal luciferase activity was observed for the luc-3' mts construct as compared to luc-3' 1 xts or ccne1-3'utr, adding further evidence for a negative role of mir-16 response sites on cyclin e expression. 20576614_1 we determined that mdm2 is a relevant target of mir-221 during chondrogenesis. 20576614_2 these findings suggest that mir-221 targets mdm2 and represses its expression during jnk-mediated signaling in the developing chick limb bud. 20576614_3 our findings indicated that mdm2 is a target of mir-221. 26647877_3 the mrna and protein expression levels of nlk were quantified in the renal cancer cells following transfection with mir-362-3p mimics. 21741600_2 moreover, co-expression of a galnt7 cdna lacking the 3'-utr was able to suppress mir-30d promotion of cell invasion, indicating that galnt7 silencing critically mediates mir-30d-檚 pro-migratory effects in melanoma . 21741600_3 overall, our in vitro and in vivo data support galnt7 inhibition as a key contributor of mir-30d-檚 pro-metastatic effects in melanoma cells. 21741600_4 that similar glycosylation changes are induced by both mir-30d upregulation and sigalnt7, and are restored by re-expressing galnt7, supports the key contribution of galnt7 repression to mir-30d-associated phenotypes. 21741600_5 these results suggest that mir-30d/30b induce il-10 at least in part by repressing galnt7, revealing an unexpected role for a single galnac transferase in linking tumor cell invasion and immune modulation. 22570635_1 furthermore, we identified drep-2 and vimar as functional targets of mir-277 that could modulate rcgg repeat-mediated neurodegeneration. 22570635_2 importantly, they also suggest that drep-2 and vimar are the functional targets of mir-277. 22570635_3 these observations suggest that mir-277 could regulate drep-2 and vimar mrnas differentially, with mir-277 regulating the expression of drep-2 mainly at the mrna level, and vimar via translational suppression instead. 22570635_4 furthermore, we identified drep-2 and vimar as the functional mir-277 targets that could modulate rcgg repeat-induced neurodegeneration. 22343731_1 luciferase assays revealed that mir-196a inhibited p27 expression by targeting one binding site in the 3'-untranslated region of p27 mrna. 22343731_2 qpcr and western blot assays verified that mir-196a reduced p27 expression at both mrna and protein levels. 22343731_3 qpcr analysis showed that the expression of p27kip1 mrna in sgc-7901 cells transfected with mir-196a inhibitor or mimics was upregulated or downregulated compared with cells transfected with control . 22343731_4 western blot analysis showed that the expression of p27kip1 protein in sgc-7901 cells transfected with mir-196a inhibitor was upregulated compared with cells transfected with negative control . 22343731_5 these data showed that mir-196a could regulate p27kip1 at both mrna and protein levels. 22343731_6 these data indicated that overexpression of p27kip1 could arrest cell-cycle progression and decrease proliferation of sgc-7901 cells, which was consistent with results of downregulated mir-196a in sgc-7901cells. 22343731_7 these data indicated that mir-196a promotes sgc-7901 cell proliferation through downregulation of p27kip1 expression. 22343731_8 these data indicated that the p27kip1 level was mostly opposite to levels of mir-196a expression in gastric cancer. 26640587_1 our present findings indicate that mir-301a-3p acts as an oncogene by directly regulating the anti-oncogene smad4, thereby playing a role in the occurrence and development of lscc. 26640587_2 therefore, the luciferase assays revealed smad4 to be a direct target of mir-301a-3p. 26640587_3 by directly regulating its target gene smad4, mir-301a-3p acts as an oncogene to play an important biological role. 23579640_1 identification of mir-221 and -222 as important regulators in genotype iv swine hepatitis e virus orf3-expressing hek 293 cells. 23579640_2 we found a significant down-regulation of mir-221 and -222 in orf3 expressing human embryonic kidney 293 cell line. 23579640_3 among the 116 candidate targets genes of mir-221 and -222 that we detected in silico, we demonstrated that the expression of the cyclin-dependent kinase inhibitor 1b, also named p27 , was directly regulated by these mirnas. 22865422_2 2, in transiently transfected sh-sy5y cells, compared with negative control, the translation of renilla luciferase was significantly reduced in the presence of mir-134 in a concentration dependent manner, suggesting mor1 mrna was the target of mir-134. 22865422_3 we speculated that mir-134 could regulate mor1 expression after allodynia in drgs and those small-diameter neurons might provide important sites for this modulation. 22865422_4 since silencing mir-134 increased mor1 expression, these data suggested that mor1 could be a target of mir-134. 26781774_1 using targetscan and pictar online software,we found that cyclin d1, the tumour repressor gene pten, and p21 were candidate targets of the mir-17~92 cluster. 26781774_2 luciferase reporter gene assay confirmed that the mir-17~92 cluster directly targets the 3'utrs of the pten and p21 genes, as shown in figure 5b and c in accordance with previous reports. 26781774_3 we found that the loss of mir-17~92 noticeably reduced akt phosphorylation in the female mice, particularly at 24 and 36 hrs post-operation , suggesting that the inhibitory effects of pten and p21 on liver regeneration overwhelmed the inductive effect of cyclin d1 in association with mir-17~92 deficiency. 26806810_1 dual luciferase assays reveal that stat3 is a direct target gene of mir-143. 26806810_3 moreover, we experimentally confirmed the role of mir-143 as a tumor suppressor in regulating the biological process by targeting stat3 in escc. 26806810_5 to explore the underlying relationship between mir-143 and stat3, we first showed that mir-143 was able to directly target the 3 - -utr of stat3, and knockdown of stat3 had similar effects as mir-143 overexpression. 25026296_1 a mechanistic study validated that mir-25 inhibition led to autophagic cell death by directly increasing ulk1 expression,an early regulator in the autophagy induction phase. 22186140_1 overexpression of mir-20a consistently resulted in the downregulation of fas expression in saos-2 cells and thus in decreased sensitivity to fasl. 22186140_2 conversely, inhibiting mir-20a in lm7 cells increased fas expression and their sensitivity to fasl. 26887441_1 with dual-luciferase assay, we confirmed that mir-150 could directly regulate the angiopoietin receptor tie-2. 26887441_2 figure 4. tie-2 is direct target of mir-150. 26887441_3 thus, we assumed that the effects of mir-150 on cell survival and claudin-5 expression were reversed after silencing tie-2. 23695671_3 these results indicated that mir-135b regulated the expression of lzts1 through a direct seed sequence interaction. 23695671_4 these results demonstrated that mir-135b-mediated lzts1 repression is possible in lung cancer cells and in other types of cancer cells. 26265472_1 it was further validated that mir-462 and mir-731 are up-regulated in a hif-1-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. 26265472_2 figure 3. mir-462 and mir-731 directly target ddx5 and ppm1da, respectively, by binding 3' utr. 21951844_2 it is further confirmed that mirna-29b downregulated the level of mcl-1 without effect on the mrna level using both qrt-pcr assays and western blot analyses. 21951844_3 moreover, we observed that enforced mir-29b expression by using a retarget mirna-29b expression vector could induce apoptosis and elevate caspase-3 activation in hmcls. 25819812_1 these modulating effects of mir-191 are achieved through its regulation of timp3. 25819812_2 we also verified the regulative role of mir-191 on timp3 expression in these 2 cell lines. 25819812_3 mir-191 overexpression led to timp3 downregulation , while mir-191 knockdown led to increased timp expression . 25819812_5 these results suggest that mir-191 can modulate cell proliferation and invasion ability of endometriosis and eaoc cells through timp3. 23770133_1 we identified the 3 ' untranslated region of mbd2 messenger rna as a target of mir-221* and mir-224. 23770133_2 collectively, these observations from cell lines and patient lymph node tissues suggest that mbd2 may be an important direct target of mir-221* and mir-224. 23770133_3 our study showed that mir-221*and mir-224 could synergistically target the same protein mbd2 in crc cells. 25188512_1 three of its targets: srsf2, plau and hic2, work in concert to relay the mir-193a-3p's impact on the bladder cancer chemoresistance by modulating the activities of the following five signaling pathways: dna damage, notch, nf-jb, myc/max, and oxidative stress. 25188512_2 srsf2, plau and hic2 are direct targets of mir-193a-3p in bca cells. in conclusion, similar to srsf2, 12 both plau and hic2 are the true direct targets of mir-193a-3p in bca cells. in this study, we have defined the roles of plau, hic2 and srsf2 genes, three direct targets of mir-193a-3p, that work in concert to relay the mir-193a-3p's impact on the bca multi-chemoresistance . 26320179_1 these data strongly suggest that mir-655, mir-300, mir-381 and mir-329 are regulated by pttg1 and participate in pttg1-mediated pituitary tumorigenesis. 26320179_2 these results show that mir-329, mir-300, mir-381 and mir-655 regulate pttg1 expression through direct binding of its 3'-utr in gh3 and mmq cells. 22454537_1 hese results suggest that hfq hexamer and sgrs form predominantly the stable 1:1 complex i under our experimental conditions, although we do not exclude the possibility that hfq binds sgrs in other stoichiometries. 20146264_1 using luciferase reporter constructs, dnmt-1 was verified as a target for mir-148a and mir-152. 20146264_2 transfection with precursors of mir-148a and mir-152 significantly modulated reporter activity in mz-cha-1 cells, whereas mir-301 precursor failed to show any effects. 20146264_3 next, the studies were repeated with random mutations in the shared recognition sequence, which resulted in abolition of the reporter activation by mir-148a and mir-152 precursors. 20146264_4 thereafter, we assessed whether ectopic expression of individual mir-148a, mir-152, and mir-301 sequences induces down-regulation of endogenous dnmt-1 protein expression. 20146264_5 taken together, these data confirm that dnmt-1 is a biologically relevant target of mir-148a and mir-152. 20146264_6 enforced expression of mir-148a and mir-152 in mz-cha-1 and kmch cells was also noted to significantly enhance rassf1a and p16ink4a expressions concomitant with decreased dnmt-1 protein level . 26606254_1 from the set of mirna-mrna interactions that were found during the development of thymocytes into pils, we identified interactions between mir- 202-3p and the ccr7 chemokine receptor and cd247 mrnas, which were previously found to be involved in the control of aggressive autoimmunity in t1d in nod mice. 26606254_2 we confirmed that mir-202-3p interacts with ccr7 or cd247 by its hybridization to their respective 3'utr sequences, which contain the predicted binding sites for this mirna. 26606254_3 in a more focused examination of pils, we observed that mir-202-3p regulates the ccr7 and cd247 mrnas. 22493679_1 mir-22 inhibited the expression of parathymosin through the 3'utr binding sites. 22493679_2 by 2d-dige, lc-ms/ms, and western blot analyses, we identified several potential targetgenes of mir-22, including parathymosin. 22493679_3 we observed an in vivo inverse correlation between mir-22 and parathymosin mrna in their tissue distribution in a rat model. 22493679_4 the phenomenon that mir-22 can reduce parathymosin protein was also observed in human hepatoma cell lines huh7 and hepg2. 22493679_5 the results indicated that mir-22 could reduce dsred mrna levels through its binding site on the parathymosin 3'-utr. 26673619_1 bioinformatic predictions and dual-luciferase reporter assays found that rhoc was a possible target of mir-372. 26673619_2 taken together, these results suggest that rhoc is a direct target of mir-372. 25103110_1 we show that the mir-15 family inhibits multiple components of the tgf-beta-pathway, including tgfbr1, smad3, smad7, p38, and endoglin. 25103110_3 knockdown of the mir-15 family in cos7 cells resulted in an up-regulation of the luciferase activity of the reporters containing the 3'-utr of tgfbr1, smad3, smad7, p38, and endoglin , suggesting that the mir-15 family is able to repress the expression of these genes by interaction with their 3'-utrs. 23728176_1 this suggests that mir-17-5p binds directly to the 3- utr of adar1. 23728176_2 taken together, it is shown that mir-17-5p and mir-432 are direct endogenous regulators of adar1, which cofunction in an additive manner. 23728176_3 finally, we identified mir-17-5p and mir-432 as the direct, independent, endogenous cellular regulators of adar1. 23728176_4 we found that cancer cells silence adar1 by overexpressing mir-17 and mir-432, which both directly target the adar1 transcript. 22000014_1 we show that linc-md1 "sponges" mir-133 and mir-135 to regulate the expression of maml1 and mef2c, transcription factors that activate muscle-specific gene expression. 21170987_1 for the first time, that mir-593* suppresses plk1 expression and reduces cell proliferation. 21170987_2 taken together with the finding that suppression of plk1 greatly reduces cell proliferation, growth suppression of ec cells by mir-593* is at least in part due to plk1 downregulation by this mir. 21170987_3 moreover, mir-593* expression levels were inversely correlated with plk1 mrna expression levels in 48 surgically resected esophageal cancer tissues . 21170987_5 thus, the exogenous mir-593* mimic reduced plk1 mrna and protein levels more markedly in hsa/c cells than in oe33 cells. 21170987_6 conversely, the exogenous mir-593* inhibitor elevated plk1 expression more clearly in oe33 cells than in hsa/c cells. 21170987_7 this result indicated that mir-593* did not affect the promoter activity of the reporter construct and suggested that plk1 mrna was degraded by mir-593*. 21170987_8 this result suggested that mir-593* interacted with both bindsg sites to regulate plk1 expression, but that the bindsg of mir-593* to the site 1 contributed more to post-transcriptional regulation of plk1 than the site 2. 20603620_1 our results reveal that mirna-185 translationally represses six1 by binding to its 3'-untranslated region. 20603620_2 in contrast, silencing of mir-185 using a specific mir-185 inhibitor in hek-293 and skov3 cells resulted in marked induction of six1 protein levels. 20603620_3 real-time pcr analysis showed that six1 mrna levels were also reduced in mir-185-overexpressing cells, indicating that mir-185 regulates six1 expression in human cancers both at the rna and protein levels. 25650716_1 downregulation of atg14 by egr1-mir152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy. 26548866_2 foxo1 expression was examined in a549 cells overexpressing mir-155. 26548866_3 the results showed that increase of mir-155 significantly decreased foxo1 mrna and protein expression, and inhibition of mir-155 significantly increased foxo1 mrna and protein expression, indicating that foxo1 was a putative target of mir-155. 19407815_3 ryhb represses the downstream part of the isc polycistron, iscsua, without affecting the upstream part, iscr. 19407815_4 this surprising observation suggests that ryhb induces a discoordination in the iscrsua polycistronic transcript, which results in specific iscr expression during iron depletion.this 19818772_1 here, we show that an additional isomer of mirna-125 translationally arrests mrna of the p53 tumor suppressor gene. 19818772_2 the basis of this activity is the high degree of sequence homology between the seed sequence of mir-125a and the 3'-utr of p53. 19818772_5 2a, ectopic expression of mirna-125a had no effect on p53 mrna levels as quantified by real time pcr thus supporting translational inhibition as the primary mode of gene silencing. 19818772_6 mirna-125a proved almost as efficacious as specific sirna against p53 in reducing protein levels . 21078976_1 mir-21 appears to targetedirectly the 3' utr of both the hmsh2 and hmsh6 mrna, resulting in significant downregulation of protein expression. 21078976_2 these results suggest that mir-21 overexpression does not affect the mrna levels of hmsh2 or hmsh6. 21078976_3 taken as a whole, these results suggest that mir-21 exerts a direct effect on the hmsh2 and hmsh6 3- utr that ultimately regulates hmsh2 and hmsh6 protein expression. 21078976_4 an inverse correlation still was evident in the remaining eight cases, highlighting the inverse correlation between mir-21 overexpression and hmsh2 downregulation in crc tumors . 21078976_5 taken as a whole, these results are consistent with the conclusion that down-regulation of hmsh2 expression by mir- 21 results in cellular resistance to 5-fu. 21078976_6 taken together, our results support a central role for mir-21-dependent down-regulation of the hmsh2-hmsh6 heterodimer mmr protein in 5-fu resistance. 22929051_1 the suppression of atg7 by mir375 elucidated how mir375 is able to block the conversion of lc3-i to lc3-ii and thus to inhibit autophagy. 26916895_1 notch1 was the name of the potential targeted gene for mir-146a in glioma. 19701247_1 the 3'utr of upa mrna is a direct target of mir-193b. 19701247_2 mir-193b might be a negative regulator for upa. 19701247_3 during breast cancer cell metastasis, the expression of mir-193b is downregulated, which in turn contributes to enhanced upa expression and invasion. 19701247_4 these results supported the bioinformatic prediction that the 3'-utr of upa mrna might be a direct target for mir-193b, and denoted that the matching site identified strongly contributed to the mirna-mrna interaction mediating the inhibition of upa expression. 19701247_5 these data are functionally relevant, and further reinforce our earlier hypothesis that downregulated mir-193b contributed to enhanced upa expression and invasiveness. 19701247_6 these findings suggest that upa is indeed a functionally important target of mir-193b, and that upa downregulation is necessary for mir-193b-mediated repression of proliferation, migration and invasion. 19701247_7 these in vivo data suggested that mir-193b is a negative regulator for upa at the post-transcriptional level. 19713529_1 thus, the two mir-128 targetsites predicted in the reelin and dcx 3'utrs are sufficient and necessary to induce the mir-128-mediated decrease of the corresponding protein products. 19713529_2 the reelin and dcx 3'utrs are direct target of mir-128. 19713529_3 these results led us to hypothesize that the observed inverse relationship between mir-128 and reelin and dcx protein expression could be due, at least in part, to a direct regulatory effect exerted by mir-128 on reelin and dcx mrnas. 19713529_4 the results of mir-128-overexpression and loss-of-function experiments are complementary and suggest that mir-128 specifically down-regulates reelin and dcx at the post-transcriptional level. 22287715_1 collectively, these data show that mir-127 target macrophage cd64 expression and promotes thereduction of lung inflammation. 22287715_2 these data display an inverse relationship between cd64 expression and mir-127 expression, indicating that cd64 is a putative target of mir-127. 22287715_3 together, these data demonstrate that cd64 is a potential target of mir-127 and is downregulated by mir-127 overexpression. 22287715_4 these suggest that mir-127 reduced the luciferase activity by binding to cd64- 3'-utr, but had no effect on cd64 mutant 3'-utr. 22287715_5 therefore, we concluded that cd64 is a bona fide target of mir-127. 22287715_6 specifically, we identify that mir-127 targeted cd64. 23141496_2 to further confirm that mir-1 binds the fabp3 3'-utr, immunoprecipitation of biotinylated mir-1 oligo was performed on homogenate from adult mouseheart followed by rna extraction and pcr analysis for fabp3 mrna. 23141496_3 consistent with the preceding results, a specific pcr signal for fabp3 was obtained, which was absent in the negative control . in addition, western blot analysis of 293 cells transduced with admir1 revealed a decrease in fabp3 protein levels upon mir-1 overexpression . 23141496_4 all together, these results demonstrate that fabp3 mrna is a direct target of mir-1. 23141496_5 for the purpose of the current study, the obtained results confirmed an inverse relationship between mir-1 and fabp3 expression, and suggest the presence of an igf-1/mir-1/fabp3 signaling axis. 23141496_6 all together, these results confirm the inverse relationship between mir-1 and fabp3 in a mousemodel of cardiac pathology. 18006846_1 the oncogenic activity of mir-27a in mda-mb-231 cells is due, in part, to suppression of zbtb10 and myt-1, which regulate specificity protein transcription factors and the g2-m chechpoint in mda-mb-231 breast cancer cells. 26843134_1 importantly, epha2 is a potential target of microrna-26b , and mir-26b expression is down- regulated in several types of cancer. 26843134_2 thus, using 97h hcc cells, epha2 mrna was verified as the target of mir-26b by the luciferase reporter assay. 26843134_3 dual luciferase reporter assay was performed to validate epha2 as an important target of mir-26b in hcc cells. 26843134_4 our luciferase reporter assay, along with previous findings, verified that epha2 mrna is a target of mir-26b . 26843134_5 western blotting analysis indicated that mir-26b exerted inhibitory effect on endogenous epha2 protein level in 97h hcc cells. 23390194_1 mir-21 was shown to directly bind to the 3'-utr of smad7 and reduce its expression in hematopoietic cells. 23390194_2 figure 2 mir-21 has a putative binding site on the smad7 3'-utr and is overexpressed in mds. 23390194_3 this was abrogated by mutation in its binding site on the utr , demonstrating a direct effect of mir-21 on the 3'-utr of smad7 . 22569260_1 therein, our data suggest that mir-223 regulates foxo1 expression and cell proliferation. 22569260_2 our data indicated that mir-223 could really targetfoxo1 mrna which led to reduction of cytoplasmic foxo1 protein. 22569260_3 mir-223 mainly down-regulates cytoplasm foxo1. 22569260_4 mir-223 target 3' untranslated region of foxo1 mrna. in nb4 cells that expressed a high level of mir-223, there was also an inverted correlation between mir-223 and foxo1 mrna expressions. 25442346_1 we corroborated that mir-15a/16 specifically bound to tlr1 3'utr and inhibited the expression of tlr1 in h358 and a549 cells.in 16982751_1 human cyp1b1 is post-transcriptionally regulated by mir-27b. 16982751_2 the expression levels of mir-27b and cyp1b1 protein in breast cancerous and adjacent noncancerous tissues from 24 patients were evaluated. 16982751_3 in most patients, the expression level of mir-27b was decreased in cancerous tissues, accompanied by a high level of cyp1b1 protein. 16982751_4 the effects of the aso for mir-27b on the enzymatic activity of cyp1b1 were examined by a p450-glo assay. 16982751_5 the enzymatic activity of cyp1b1 was increased by the electroporation of the aso for mir-27b in mcf-7 cells in concentration- and time-dependent manners . in contrast to the cyp1b1 protein level, no relationship was observed between the cyp1b1 mrna level and the mir-27b level in human breast tissues . 16982751_6 these results suggested that cyp1b1 is post-transcriptionally regulated by mir-27b. 16982751_7 the decreased expression of mir-27b would be one of the causes of the high expression of cyp1b1 protein in cancerous tissues. 19546220_1 interestingly, mir-27b and its putative targetgene, st14 , had inverse expression pattern in breast cancer cells. 19546220_2 expression levels of st14 showed an inverse relation with the expression pattern of mir-27b at both the rna and protein levels , suggesting that st14 may be negatively regulated by mir-27b. 19546220_3 these data suggest that mir-27b specifically binds the 3'-utr region of st14 and reduces st14 expression. 19546220_4 our data indicated that 3'-utr of st14 is specific to mir-27b. 23108656_1 our results showed that enos is the direct target of mir-155 and tnfalpha can increase mir-155 expression, indicating mir-155 may contribute to tnfalpha-induced enos downregulation. 23108656_2 these fidings indicated that mir-155 is an essential regulator of enos expression and endothelium-dependent vasorelaxation. 23108656_4 mir-155 downregulated endogeneous enos expression in huvecs by destabilizing enos mrna. 23108656_5 these data indicated that enos is a direct target of mir-155. 23125021_2 we found that mir-10b* controls cell cycle progression and proliferation by targeting the expression of bub1, plk1 and ccna2, and that low expression levels of these three genes are, to various extents, predictive of less aggressive disease and of longer relapse- and metastasis-free survival. 23125021_3 mir-10b* targets the 3 0 -utr region of bub1, plk1 and ccna2 transcripts . 19188439_5 the cardiomyocyte-restricted microrna mir-1 inhibited translation of calmodulin-encoding mrnas via highly conserved target sites within their 3'-untranslated regions. in keeping with its effect on calmodulin expression, mir-1 downregulated calcium-calmodulin signaling through calcineurin to nfat. 19188439_6 mir-1 also negatively regulated expression of mef2a and gata4, key transcription factors that mediate calcium-dependent changes in gene expression. 19188439_8 our data indicate that mir-1 regulates cardiomyocyte growth responses by negatively regulating the calcium-signaling components calmodulin, mef2a, and gata4. 23389994_1 to determine whether mir-520a/b/e directly target the 3'-utr of pfkp mrna, we assessed a luciferase reporter vector containing the 3'-utr sequence of pfkp, including the predicted binding site for mir-520a/b/e in sk- hep1 cells. 23389994_2 luciferase activity was significantly inhibited by the pfkp 3'-utr sequence when only mir- 520a/b/e were cotransfected . 23389994_3 however, luciferase activity was not inhibited by a mutant 3'-utr sequence , strongly demonstrating that mir-520a/b/e directly target the 3'-utr sequence of pfkp mrna and inhibits the expression of pfkp. 23389994_4 when sk-hep1 cells were treated with mir-520a-3p, mir-520b, and mir-520e , expression of pfkp was significantly down-regulated , suggesting that pfkp might be a direct target of mir-520a/b/e. 25597268_1 then we found that vegf enhanced the invasiveness of and inhibited apoptosis in ovarian cancer cells as assessed by transwell invasion assays and annexin v-fitc immunostaining, respectively. 25597268_3 furthermore, using the dual-luciferase report assay system, we demonstrated that mir-205 targeted ezrin and lamin a/c. 26676955_2 taken together, these results demonstrate that mir-764-3p down-regulates sf-1 expression through destabilizing its mrna. in this study, we have found that mir-764-3p inhibits e 2 biosynthesis in mouse ovarian granulosa cells by directly targeting the orphan nuclearreceptor sf-1. 26071245_1 taken together,these findings suggested that hgf and smad7 expression could be suppressed by mir-16 via binding to their 3'utrs. 21915098_1 through transcriptome profiling, we identified three novel mir-101 targets, stmn1, rab5a and atg4d. 26045791_1 mir-570 represses klf9 expression through targeting its 3'-utr. 26045791_2 a. prediction of mir-570 binding sites in the 3'-utrs of human klf9 gene by mirwalk software. 26045791_4 western blot analysis of klf9 in a549 and nci-h358 cells transfected with mir-570 mimics or negative control .representative 26823713_1 in addition, the sex-determining region y-related high mobility group box 4 is identified as a target of mir-211 in gc cells, and sox4 expression levels was inversely correlated with mir-211. 26823713_2 taken together, these results indicated that sox4 gene was one of the direct targets of mir-211. 26823713_3 these results suggested that knockdown of sox4 play the similar effects as mir-211 over-expression, sox4 is a functionally important target of mir-211. 26019450_1 the 3'-utr of cdkn2d contains the seed regions for mir-451 at the position of base 240 nt - 246 nt .1a. similarly, the 3'-utr of map3k1 contains the seed regions for mir-451 at the position of base 6270 nt - 6278 nt . 26019450_2 subsequent western blot analysis indeed showed that cdkn2d and map3k1 expression was down-regulated in ec9706 and kyse150 cells following transfection with the mir-451 mimics. 26019450_3 these data indicate that mir-451 negatively regulates cdkn2d and map3k1 expression by directly binding to putative binding sites in the 3'-utr. 26019450_4 our results thus demonstrated that cdkn2d and map3k1 are direct targets of mir-451. 23091630_1 glyceraldehyde-3-phosphate dehydrogenase and -beta-actin are target of mir-644a. 23091630_2 here, we show that gapdh and -beta-actin are direct target of mir-644a. 23091630_4 mir-644a downregulates gapdh and -beta-actin mrna expression. 23091630_5 taken together, these data show that mir-644a represses gapdh and -beta-actin expression by directly interacting with its targetsequence in the respective 3'-utrs. 23091630_6 mir-644a downregulates gapdh and -beta-actin protein expression. 19702828_1 our studies show that microrna-9 is downregulated in human ovarian cancer relative to normal ovary, and overexpression of mir-9 suppresses cell growth in vitro. 19702828_2 furthermore, the 3'-utr of nf-kappab1 mrna is found to be regulated directly by mir-9, demonstrating that nf-kappab1 is a functionally important target of mir-9 in ovarian cancer cells. 19702828_3 when mir-9 is overexpressed in ovarian cancer cells, the mrna and protein levels of nf-kappab1 are both suppressed, whereas inhibition of mir-9 results in an increase in the nf-kappab1 expression level. 19702828_4 ovarian cancer tissues display significantly low expression of mir-9 and a high level of nf-kappab1 compared with normal tissues, indicating that regulation of nf-kappab1 by mir-9 is an important mechanism for mir-9 to inhibit ovarian cancer proliferation. 26433199_1 high levels of mir-451/mir-21 in gbm-evs were transferred to microglia with a decrease in the mir-451/mir-21 target c-myc mrna. 26433199_2 a number of targets are regulated by mir-451, including cab39, mif, and c-myc. 26433199_6 fig. 4. gbm-derived evs increase mir-21 and mir-451 levels and decrease c-myc mrna levels in primary mouse microglia. 22194877_1 luciferase assays demonstrated that these mirnas downregulates bdnf expression and that the presence of the variant alleles of two single nucleotide polymorphisms mapping in bdnf 3'utr specifically abrogates mirnas targeting. 22194877_2 the activity of the reporter plasmid with ancestral alleles at polymorphic sites in the presence of each of the two mirnas was significantly lower than those of cells transfected with mir-control or unmodified prl-tk vector, indicating that bdnf was specifically down-regulated by mir-26a and mir-26b mirna mimics . 22194877_3 from these results we could conclude that human bdnf is targeted by mir-26a and mir-26b which bindto the same seed sequence. 22730212_1 together, these results indicated that mir-17-5p functions as a tumor suppressor in cervicalcancer cells by targeting tp53inp1. 22730212_2 here, we identified tp53inp1 as a target of mir-17-5p. 22730212_3 in this study, we demonstrated that mir-17-5p targeted the 3'utr of tumor protein p53-induced nuclear protein 1 mrna transcripts and downregulated its expression in cervical cancer cells. 22730212_4 all of these results indicated that mir-17-5p can directly bindthe 3'-utr of tp53inp1 transcripts. 22730212_5 these results clearly indicated that mir-17-5p could directly targetthe 3'-utr of tp53inp1 mrna and downregulate its expression at a post-transcriptional level. 22730212_6 these results demonstrate that tp53inp1 is a mediator of mir-17-5p-induced cell growth suppression and apoptosis promotion in cervical cancer cell lines. 22730212_7 this concordant inverse correlation between tp53inp1 and mir-17-5p was also observed in four kinds of cervical cancer cell lines . 26451614_2 as shown in figure 3c, these mutations completely abolished the repressive effects of mir-573 on fgfr-1 3- utr activities. 26451614_3 collectively, our data suggests that mir-573 directly suppresses fgfr1 expression in pca cells. 26451614_4 further, our study identified fgfr1 as a key downstream target of mir-573. 24117217_1 furthermore, mir-19b led to increased cell survival through up-regulation of the nfat target gene encoding alpha-crystallin-b and repression of the pro-apoptotic gene bim under er stress conditions. 25172909_1 the mir-143 and anti-mir-155 transfection resulted in a significant cell apoptosis. 25172909_2 the expression of dicer was decreased with hk2 accumulating in mouse lung tissues under hypoxia identified by immunohistochemistry. 20489169_1 stat5a is a novel mir-222 targetin ecs challenged with il-3 and bfgf. 20489169_2 further indicating that stat5a is mostly regulated by mir-222 during inflammation-mediated neoangiogenesis. 20489169_4 moreover, the finding that no changes in c-kit and p27kip1 protein expression could be detected again identifies stat5a as the main regulator of neovascularization, which is mostly regulated posttranscriptionally by mir-222. 25517751_1 the von hippel-lindau tumor suppressor represses trpm3 directly through mir-204 and indirectly through another mir-204 target, caveolin 1 . 23305226_1 microrna-34b inhibits pancreatic cancer metastasis through repressing smad3 26722476_1 furthermore, e2f3 was identified as a direct target of mir-503 in crc cells and down-regulation of e2f3 had a similar effect as mir-503 overexpression on crc cells. 26722476_2 mir-503 inhibits cell proliferation and induces apoptosis by directly targeting e2f3 in crc cells, indicating its potential application in crc diagnosis and therapy. 26722476_4 these results collectively suggest that mir-503 plays its suppressive role in crc by direct targeting e2f3. 26903388_1 in contrast, speci-fic antagomir-mediated inhibition of hsa-mir-520h did not change abcg2 protein levels in this experimental setting, thereby indicating that hsa-mir-328 and hsa-mir-519c rather than hsa-mir-520h may play a role in post-transcriptional abcg2 regulation in hek293-tet-on cells . 26824181_2 there is a conservative 7nt mir-10a responsive element in 3'-utr of bim . 26824181_3 moreover, we found that the expression level of bim was inverted with that of mir-10a in hec-1b, hela, hek-293, hek-293t and vct cells. in order to confirm the binding sites of mir-10a in the 3'-utr of bim, the conservative 7nt mir-10a responsive element in 3'-utr of bim was mutated . 26824181_4 the enzyme activity was significantly reduced in cells co-transfected with mir-10a mimic and bim-pgl compared with bim-pgl-mu , implying that the seed sequence of mir-10a could specially recognize mir-10a responsive element in the 3'-utr of bim. 26824181_5 bim mrna level was significantly reduced by mir-10a mimic and raised by mir-10a inhibitor 26859226_3 consistent with previous studies, we found higher expression of these targets in mir-139-5p ko mice than that of wt mice, but most of them didn-檛 exhibit statistical significance. 26859226_4 among these targets, we found that rap1b and nf-kappab were the two most overexpressed genes in the context of mir-139-5p deficiency. in the absence of mir-139-5p, upregulated production of inflammatory and tumorigenic factors drives the transformation of epithelial cells and promotes colitis-associated tumorgenesis. 24531888_1 a luciferase reporter assay demonstrated that atm was a direct target of mir-181a, mir-181a mimics transfection down regulated atm mrna and protein expression. 25883224_1 validation experiments identified timp-2 as a direct target of mir-221/222. 25883224_2 thus, timp-2 is a pivotal target of mir-221/222-induced pancreatic cancer cell invasion. 25883224_3 furthermore, we observed an increase in mmp-2 and mmp-9 after mimic transfection and showed that timp-2 is a direct functional target of mir-221/222. 18607543_1 to further substantiate cdk6 as a target of mir 124, we transfected daoy cells with mir 124 precursors followed by western blotting for cdk6. 18607543_2 re-expression of mir 124 in daoy medulloblastoma cells decreased expression of cdk6 protein . 18607543_3 together these data indicate that cdk6 is a targetfor mir 124 in medulloblastoma. 26823826_1 curcumin could significantly inhibit the proliferation of mg-63 cells and the expression levels of mirna-138 target genes smad4, nfkappab p65 and cyclin d3 in mg-63 cells ; overexpression of hsa-mir-138 down-regulated the expression levels of smad4, nfkappab p65 and cyclin d3 compared with the treatment of curcumin, while inhibition of hsa-mir-138 up-regulated the expression levels of smad4, nfkappab p65 and cyclin d3. 26823826_3 rt-pcr results showed that compared with curcumin group, overexpression of hsa-mir-138 could down-regulate the expression levels of smad4, nfkappab p65 and cyclin d3 in mg-63 cells, while hsa-mir-138 inhibitor could up-regulate the expression levels of smad4, nfkappab p65 and cyclin d3 in mg-63 cells . 25104088_2 we subsequently identified the oncogene pim-1 as a direct target of mir-486-5p in bc. 25104088_3 overexpression of pim-1 attenuated the function of mir-486-5p in bc cells. 25104088_4 together, we conclude that mir-486-5p exerts its antiproliferative function by directly downregulating pim-1 expression. 25341040_1 sirna knockdown of ezh2 increased mir-31 expression and decreased the antiapoptotic protein e2f6 , resulting in the sensitization of prostate cancer cells to docetaxel-induced apoptosis. 19074876_4 4d, 3'-utrs from these 18 genes were regulated by mir-192 but not by mir-192mut, indicating that these 3'-utrs can confer regulation of a heterologous gene by mir-192. 19074876_5 furthermore, mir-192 mediated suppression of cdc7 might induce p21, providing an additional mechanistic explanation for how mir-192 might function in the p53 pathway. 21317927_1 anp32a and smarca4 are direct target of mir-21. 21317927_2 concluding from these results, anp32a and smarca4 protein levels correlate inversely with mir-21 expression. 21317927_3 figure 3 anp32a and smarca4 are regulated by mir-21 in various cell lines. 21317927_4 taken together, our results indicate that anp32a and smarca4 are direct target of mir-21. 21317927_5 taken together, these results suggest that anp32a accounts for the various biological effects of mir-21 in different cell types. 26851791_1 a significant decrease of luciferase activity upon let-7c transfection was observed, suggesting that let-7c suppressed stat3 directly in alveolar macrophages. 26851791_2 in addition, we also found protein and mrna expression levels of stat3 were significantly decreased in let-7c transfected cells. 23006329_2 here, we report that mir-182 was overexpressed in a different set of gliomas with relatively lower mir-30e* expression and that mir-182 directly suppressed cylindromatosis , an nf-κb negative regulator. 23006329_3 analyses by mirnp ip assay revealed a selective association of mir-182 with cyld . 23006329_4 notably, the inhibitory effect of mir-182 on the activity of luciferase reporter linked with the 3'-utr of cyld was abolished by a mir-182 inhibitor. 23006329_5 collectively, these results established cyld as a bona fide target of mir-182. 26792278_1 the akt/gsk3b pathway contributed to orai1 effects in crc cells, and orai1 was a direct target of mir-519, a microrna not previously reported to be involved in both crc tissues and cell lines. 26792278_2 further investigations indicated that orai1 is a direct target of mir-519, a microrna that has previously been shown to inhibit growth and cell survival. 26792278_3 these data strongly suggest that mir-519 is one of the upstream molecules regulating orai1 expression in crc. 26792278_4 additionally, high orai1 expression in crc is at least partly attributed to posttranscriptional regulation by mir-519. 22042971_1 the results also showed that the luciferase activity in cells transfected with the o vector and mir-221 or mir-222 was fully recovered compared with that in the negative control , indicating that mir-221 and mir-222 directly targetkit mrna. 22042971_2 the expression of phospho-akt, as measured by a phospho-akt-specific antibody, was decreased by mir-221 and mir-494 overexpression, with the downregulation of phospho-akt being much larger after mir-494 overexpression than after mir-221 overexpression. 22042971_3 the pattern of changes in phospho-stat3 expression was similar to that of phospho-akt expression after mir-221 and mir-494 overexpression and the decreases were larger after mir-494 overexpression. 26666173_1 ucp2 was identified to be a direct target of mir-214. 26666173_2 mir-214 increased the sensitivity of breast cancer cells to tam and ful through inhibition of autophagy by targeting ucp2. 26666173_3 mir-214 was found to downregulate ucp2 by targeting the site in 3'-utr of ucp2 gene determined by dual luciferase reporter assay . 26666173_4 these results suggested that mir-214 might directly bind to the 3'-utr of ucp2 and modulate ucp2 expression. 25017423_1 we predicted and identified the prkcd gene as one of the targets of mir-224-5p in mediating the primary chemo-resistance of ovarian cancer patients. 25017423_2 western blot analyses revealed that mir-224-5p negatively regulated prkcd expression at both cisplatin-resistant parental cell and its sensitive variant cell levels . in the present study, we demonstrated that mir-224-5p could negatively regulate the expression of prkcd, and together with prkcd, they can serve as novel predictors and prognostic biomarkers for opsc patient response to overall disease-specific survival . 22988237_1 the luciferase activity of mre -luc was reduced ~30% upon cotransfection with mir-302c, while the activity of the mutated construct was not affected , demonstrating that the mir-302 mre in the bmprii mrna 3'-utr can be targeted by mir-302c and possibly other members of the mir-302 family of mirnas. 22988237_2 this result demonstrates that forced expression of mir-302c negatively regulates the bmp signaling pathway, likely due to the decrease in bmprii level . 22988237_3 immunoblot analysis confirmed that mir-302c led to a reduction of bmprii protein . 22988237_4 these results demonstrate that bmprii is a novel target of mir-302c. 24503542_1 it was seen that over-expression of mir-542-3p leads to repression of bmp-7 and inhibition of bmp-7/pi3k- survivin signaling. 23466643_2 over-expression of mir-371-5p and knockdown of prpf4b promotes cell growth by accelerating the g1/s transition in hcc cell lines. 23466643_5 fig. 3. prpf4b is a direct target of mir-371-5p. 20711193_1 ikkalpha mrna was a target of mir-15a, mir-16 and mir-223. 20711193_2 decrease in the expression of mir-15a, mir-16 and mir-223 correlated with the increase in ikkalpha protein expression. 20711193_3 thus, a decrease in mir-15a, mir-16, and mir-223 expression levels correlated with rising ikkalpha protein expression in macrophages, and suggested that these mirnas could function as modulators of ikkalpha mrna and protein expression. 25138550_1 the post-transcriptional repression of rankl by microrna-17/20a was further confirmed by the luciferase reporter assay. 25138550_2 in this study, we identified that rankl is a target gene of microrna-17/20a. 25138550_3 here we demonstrated that gcs can increase rankl expression through down-regulating microrna-17/20a in osteoblasts, which enhances osteoclastogenesis and bone resorption. 25138550_4 inthecurrentstudy, we confirmed that dex acts on osteoblasts to up-regulate the expression of rankl by decreasing microrna-17/20a, which indirectly affects osteoclast differentiation and bone resorption. 25551793_1 tgfbr2 was identified to be the downstream target of mir-301a. 25551793_2 knockdown of tgfbr2 in cells treated by mir-301a inhibitor elevated the previously abrogated migration and invasion. 25551793_3 combined together, these results suggested that mir-301a suppressed tgfbr2 in crc cells. 25551793_4 these data demonstrated unambiguously that mir-301a suppressed tgfbr2 protein expression via targeting its specific rna binding site. 25551793_5 conclusively, these results suggest that downregulation of tgfbr2 is involved in mir-301a-induced metastasis and invasion; tgfbr2 is a functional target of mir-301a. 26134897_1 mir-135a and mir-135b target the 3'utr of gsk3 and inhibit gsk3 expression. 26134897_2 glycogen synthase kinase 3-beta is a target gene of mir-135a and mir-135b. 23867971_1 mir-203 down-regulated vascular endothelial growth factor alpha expression by directly targeting its 3'-untranslated region. 23867971_3 3d and e, mir-203 overexpression down-regulated vegfa expression at both the mrna and protein levels. 23867971_4 in contrast, mir-203 knockdown using anti-mir203 in hela cells, which have high endogenous mir-203 levels, significantly increased vegfa expression. 23867971_5 these results provide evidence that mir-203 directly recognizes the 3'-utr of vegfa mrna and inhibits its expression. 21745735_1 tagln2 as a direct targetfor both mir-1 and mir- 133a in rcc. the mrna and protein expression levels of tagln2 were markedly downregulated in the mir-1 and mir-133a transfectants in comparison with the controls . 21745735_2 subsequently, we performed a luciferase reporter assay to determine whether tagln2 mrna has actual targetsites for mir-1 and mir-133a. 21745735_3 we used a vector encoding full-length 3' utr of tagln2 mrna and found that the luminescence intensity was significantly reduced in the mir-1 and mir-133a transfectants . 21745735_4 these results indicate that tagln2 is a common targetgene for both mir-1 and mir-133a. 23092882_1 in transient transfection experiments, the luciferase activity of a mek1 3'utr luciferase reporter construct was reduced in the presence of mir-497, and mutation of the predicted mir-497 binding site restored activity. 23092882_2 mir-497 also decreased protein levels of raf1 and erk1 but not erk2. 23092882_3 in summary, we have shown for the first time that mir-497 is one of the regulators of mek1, in addition to raf1, and plays a part in modulating the inflammatory signal of il-1 to one of its targetgenes. 23092882_4 mir-497 suppresses expression of mek1 protein. 23092882_5 the mir-497 targetsites in the mek1 3'utr. 23092882_6 raf1 is targeted by mir-497 and mir-125b and . 17072344_1 this anti-mir-21-mediated cell growth inhibition was associated with increased apoptosis and decreased cell proliferation, which could be in part owing to downregulation of the antiapoptotic bcl-2 in anti-mir-21-treated tumor cells. 22072783_1 we showed that microrna mir29 suppresses dnmt activity and thus induces expression of cox2 and pge2. 22072783_2 the mirnas of the mir29 family have been shown to downregulate the expression of dnmt3a and dnmt3b . 22072783_4 following transfection with mir29s, total dnmt catalyzing activity significantly decreased in the nuclear extract of a549 cell lysates . 22072783_5 among the mir29 family members, mir29b most efficiently reduced dnmt catalyzing activity . 22072783_6 additionally, we measured the expression of cox2, dnmt3a, and dnmt3b in a549 cells transfected with mir29a, mir29b, and mir29c and found that cox2 expression was increased and dnmt3a and dnmt3b were decreased when the three mir29s were present . 22072783_7 these results indicate that mirnas of the mir29 family induce cox2 expression by regulating dnmt expression. 22072783_8 these results demonstrate that the mir29b upregulation occurs early after virus infection and influences dnmt expression in pbmcs. 22072783_9 together, the results proved the important role of mir29 in dnmt downregulation, cox2 promoter demethylation, and cox2 expression during influenza virus infection. 22308344_1 further studies showed that prelamin a expression, but not lamin c expression, is down-regulated by a brain-specific microrna, mir-9. 22308344_2 fluorescence microscopy revealed that mir-9, but not mir-129, reduced lamin a expression in transfected hela cells . 22308344_3 the mir-9 overexpression studies, along with the luciferase reporter studies, supported the idea that mir-9 binds to the prelamin a 3- utr and down-regulates prelamin a expression in the brain. 23139385_1 microrna-101 is a small non-coding rna that regulates the mapk response by targeting mkp-1 mrna 3'-utr, and affects the secretion of the downstream inflammatory cytokines. 23139385_3 mir-101 is a small non-coding rna that directly target and suppresses mkp-1 to regulate the activation of mkp kinases and subsequent production of cytokines in response to lipopolysaccharide stimulation. 19509158_1 mir-21 is an independent prognostic indicator for tscc, and may play a role in tscc development by inhibiting cancer cell apoptosis partly via tpm1 silencing. 26799631_1 we found that ephb2 is a direct target of mir-204 among mirnas that were upregulated with age. in this case, the mir-204 mimic did not induce a significant change in luciferase activity indicating a specific interaction between the mir-204 and ephb2 3 ' utrs. 26799631_2 sirna against ephb2 as a positive control resulted in decrease in nr1 surface to total ratio by 77% compared with scramble , suggesting that mir204 is involved in the regulation of surface expression level of nr1 through ephb2. 26799631_3 we demonstrate that ephb2 is decreased in aged hippocampus concomitant with mir-204 upregulation, ephb2 is a target of mir-204 in hippocampal neurons and mir-204 reduces both total nr1 expression and surface expression in hippocampal neurons. 18952787_1 gcvb negatively regulates sstt mrna in an hfq-dependent mechanism.gcvb 18952787_3 the region of gcvb complementary to sstt mrna is the same region of gcvb identified to regulate the dppa and oppa mrnas.that 18952787_4 gcvb and mrna pairing is also the regulatory mechanism employed by gcvb for negative regulation of sstt mrna and that this regulation is dependent upon hfq. 25627001_1 further, mir-148b induced cells apoptosis by activating caspase- 3 and caspase-9, and induced s phase arrest by regulating cyclind1 and p21, and also inhibited cell invasion. 25627001_2 data from the dual-luciferase reporter gene assay showed that wnt1 was a direct target of mir-148b, and overexpressed wnt1 inversely correlated with mir-148b levels in hcc tissues. 25627001_3 silencing of wnt1 inhibited the growth of hcc cells, and also induced cells apoptosis and inhibited invasion, which is consistent with the effects of mir-148b overexpression. 25627001_4 mir-148b downregulated expression of wnt1, -beta-catenin and c-myc, while upregulated e-cadherin expression. 20056941_1 we then confirmed that mir-133b directly target the 3'utrs of both mcl-1 and bcl2l2. 25385144_1 the inhibition of hif-1alpha decreased mir-210 expression and autophagy. 25385144_2 silencing of mir-210 upregulated bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. 25385144_3 under hypoxia, hif-1alpha induces mirna-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating bcl-2 expression in colon cancer cells. 19509156_2 strong mir-21 expression was also observed in cancer-associated stromal fibroblasts, suggesting mir-21 induction by cancer-secreted cytokines. 19509156_3 protein expression of pdcd4, a mir-21 target, was inversely correlated with mir-21 expression, confirming that mir-21 is indeed a negative regulator of pdcd4 in vivo. in the endoscopic samples, mir-21 expression was very high in malignant adenocarcinomas but was not elevated in nontumorigenic polyps. 23513069_1 akt1 are direct targets of mir-342-5p. 23513069_2 mir-342-5p directly targets akt1 through its 3'-untranslated region. 23513069_3 akt1 suppression by mir-342-5p induces proinflammatory mediators such as nos2 and ii6 in macrophages via the upregulation of mir-155. 23513069_4 overall, these results indicate that mir-342-5p primarily regulates the proinflammatory activation of macrophages by targeting akt1. 23513069_5 his indicated that an abundance of bmpr2 mrna may regulate akt1 in unstimulated macrophages by competing with akt1 for mir-342-5p binding. 26675712_1 therefore, our data are consistent with the hypothesis that mir-132 represses paxillin protein levels via direct targeting of the 3'-utr of paxillin. 26675712_2 in summary, these results demonstrated that mir-132 inhibited the expression of paxillin through posttranscriptional repression. in this study, our data showed that the overexpression of mir-132 significantly reduced the activity of a luciferase reporter containing the 3'-utr sequence of paxillin, which has been confirmed as a target gene of mir-132. 19665576_2 mir-584 specifically binds to the lfr mrna-3 ' -utr. 19665576_3 the ability of mir-584 to bind lfr mrna was evaluated by luciferase reporter assay. 19336521_9 to investigate the relation between runx3 and mir-532-5p, anti-mir-532-5p was transfected into melanoma lines. 19336521_10 inhibition of mir-532-5p up-regulated both runx3 mrna and protein expression.conclusions: 19336521_11 runx3 is down-regulated during melanoma progression and mir-532-5p is a regulatory factor of runx3 expression. 21778427_1 by in silico screening of expression data with predicted mir-23 targetsites combined with in vivo testing, we identified hyaluronic acid synthase 2 , icat, and tmem2 as novel direct target of mir-23. 21778427_2 we only observed strong silencing of the gfp signal with mir-23 mimics when the has2, icat, and tmem2 3'-utr sequences were present . 26104682_1 a computer prediction of the conserved and mutated binding sites within the 3' utr of human rybp mrnas for mir-9. 26104682_3 after alignment, we found a putative binding site of mir-9 in the 3'-utr of rybp mrna . 26104682_4 to validate whether mir-9 targets rybp, we first cloned the wild-type or mir-9-binding site-mutant rybp 3' utrs into a pmir-reporter plasmid and co-transfected these constructs into 293 t cells with an mir-9 mimic or a mimic-control. 25674218_1 knockout of mcl-1 caused apoptosis of the colonic epithelial ht29 cells. in addition, mir-29a regulated intestinal epithelial apoptosis by down-regulating the expression of mcl-1. 20522784_1 using luciferase reporter assay, we show that krt16, krt17, dlx3, and fgf10 serve as direct mir-31 target. 12975324_1 it is clear from the results that, when ryhb is expressed at high levels, only 3 min are sufficient to completely eliminate the target sodb message.evidences 12975324_2 show that the paired region of ryhb-sodb interaction is not the site of the initial cleavage, and rnase e is necessary for degradation of ryhb targets.it is not clear whether hfq leaves this complex, but both ryhb and its target mrna are rapidly degraded; degradation is dependent upon rnase e. 20501828_2 these in vitro findings were confirmed by an analysis of human hcc tissues, which revealed an inverse correlation linking mir-199a-3p and mtor as well as a shorter time to recurrence after hcc resection in patients with lower mir-199a-3p expression. 20501828_3 these results suggest that tactics to regulate mtor and c-met by elevating levels of mir-199a-3p may have therapeutic benefits in highly lethal cancers such as hcc. 20799954_1 ddr1 was shown to be a direct target of mir-199a-5p by luciferase reporter assay. 20799954_2 mir-199a-5p differentially regulates the expression of ddr1 in hepg2 and snu-182 cells. in mrna stability assays we established that mir-199a-5p-mediated regulation of ddr1 in hepg2 cells is mainly achieved by degradation of ddr1 mrna . in contrast, transfection of mir-199a precursor in another hepatoma cell line, namely snu-182, was not associated with an alteration of ddr1 mrna expression . 20799954_3 however, a notable decrease of ddr1 protein levels became evident after mir-199a-5p precursor transfection . 26577184_1 moreover, spearman's test showed a moderate inverse correlation between cplx1 and mir-185 expression levels of bd, nbd patients and healthy controls. 26577184_2 mir-185 and cplx1 levels also showed significant correlation when only bd and nbd patients- expression levels were evaluated. 26516138_1 increased mir-451 expression may negatively regulate bcl-2 mrna and protein expression, followed by affecting the protein expression of caspase 3, and accelerate the apoptosis in breast cancer, indicating that mir-451 might influence the drug resistances of the paclitaxel-resistant breast cancer cell line. 26516138_2 bcl-2 as a direct target of mir-451. 25427715_1 mir-378a-3p over-expression in an rms-derived cell line suppressed igf1r expression and affected phosphorylated-akt protein levels. 25427715_2 ectopic expression of mir-378a-3p caused significant changes in apoptosis, cell migration, cytoskeleton organization as well as a modulation of the muscular markers myod1, myor, desmin and myhc. in addition, dna demethylation by 5-aza-2'-deoxycytidine was able to up-regulate mir-378a-3p levels with a concomitant induction of apoptosis, decrease in cell viability and cell cycle arrest in g2-phase. 25639236_1 these results demonstrate a novel role for mir-15a in neuronal development and provide a missing link in the regulation of bdnf by mecp2. 25639236_2 mecp2 is known to repress the expression of bdnf by directly binding to its promoter. 25639236_3 we and others have shown that mecp2 regulates the expression of mirnas and among them there are three bdnf-恡argeting mirnas: mir-206, mir-495, and mir15a. 26153982_2 to validate that smad3 is a direct target of mir-23b, smad3 luciferase reporters were constructed with wild-type and mutated 3'-utr of smad3. 1621097_2 the conformations of tar rna and of tar with an arginine analog specifically bound at the binding site for the viral protein, tat, were characterized by nuclear magnetic resonance spectroscopy. 23327190_1 overexpression of mir-125a/b significantly inhibited aldh1a3 and mcl1 expression, reduced cell survival, and increased cell apoptosis in ht29-taxol cells. 21211043_2 out of four mirnas at del , only mir-378 and mir-146a showed reduced gene expression in the patients. 14739933_1 the article showed a novel use of hfq in the regulation by small rna. the binding of hfq to its mrna target leads to changes in mrna structure that are ritical for access by the small regulatory rna.hfq alters the secondary structure of sodb mrna, but not that of ryhb. 14739933_2 thus, in vivo, the modification of the binding site of hfq on sodb strongly impairs the repression by ryhb. 14739933_3 this is consistent with the important effects observed in vitro of hfq binding on sodb mrna. 21351259_2 the identification of tumor-suppressive mirnas, mir-145, mir-133a and mir-133b, directly control oncogenic fscn1 gene. 21351259_4 the expression level of fscn1 mrna was significantly decreased in the 2 escc cell lines transfected with mir-145, mir-133a and mir-133b . 21351259_5 the protein expression level was also markedly reduced in escc cell lines transfected with mir-145, mir-133a and mir-133b transfectants . 21351259_6 this is the first study to show that mir-145 and mir-133a/b directly regulate fscn1 and contribute to cellular proliferation and invasion in escc. 26820803_1 these data demonstrates the presence of functional binding sites for mir-29a, mir-29b1, mir-410, and mir-1277 on the human lpl transcripts harboring the wild-type hap1 haplotype, disrupted by the minor alleles of the hap4 haplotype snps. 26820803_2 functional validation performed in hek-293t cells using luciferase expression constructs with various lpl 3 ' utr allele combinations demonstrated a binding of mir-29, mir-1277 and mir-410 on hap1, lost on hap4. 26820803_3 we further established that the hap1 haplotype endowed functional binding sites for mir-29a, mir-29-b, mir-410 and mir-1277 and demonstrated that these binding sites were abolished by genetic variation within hap4 haplotype. 23935993_1 by sequence analysis we found a binding site for mir-146a in the sod2 mrna 3' utr, and a luciferase reporter assay confirmed that mir-146a can interact with this sod2 regulatory region. 23935993_2 the reporter constructs were co-transfected with mir-146a mimics in pc12 cells, and the results demonstrated that mir-146a mimics could down regulate the luciferase activity by 29.7% versus negative control group . in addition, a study using luciferase reporter assay revealed that mir-222 could bind the sod2 3' utr, and the expression of sod2 was reduced in a carcinoma cells when transfected with ectopic mir-222 . in this study, knockdown of mir-382 could attenuate tgf-b1 induced down-regulation of sod2 protein, and 3' utr reporter assay showed mir-382 could target sod2 mrna . 22532850_1 fas apoptosis inhibitory molecule is directly regulated by mir-133b. 22532850_2 comprehensive analysis, encompassing global rna or protein expression profiling performed by microarray experiments and pulsed stable isotope labeling with amino acids in cell culture , led to the discovery of the antiapoptotic protein fas apoptosis inhibitory molecule as immediate mir-133b target as demonstrated by luciferase reporter assays, coupling of entire gstp1 3'-utr to renilla luciferase specifically rendered it less active after cotransfection of mir-133b. 26870610_1 together, our data conclusively demonstrate that runx1 is a direct target of mir-27b in pk-15 cells. 26049093_1 these data indicated that let-7a could negatively regulate uhrf1 expression. 26049093_2 therefore, uhrf1 was a target for let-7a. 19155478_1 of those ifn-gamma-down-regulated mirnas, we identified microrna-513 with complementarity to the 3'-untranslated region of b7-h1 mrna. 19155478_2 mir-513 target a potential binding site in the b7-h1 3'- utr resulting in translational suppression. 19155478_4 mir-513 is capable of targeting a predicted site in the b7-h1 3'-utr, resulting in translational repression. 19155478_5 transfection of an antisense to mir-513 induces b7-h1 protein expression. 19155478_6 taken together, our data indicate that mir-513 mediates translational repression of b7-h1, a process that may account for the posttranscriptional suppression of b7-h1 in resting human cholangiocytes. 22105995_1 taken together, our data point toward an important role for mir-19a and mir-19b in the regulation of il-6 and mmp3 release by controlling tlr2 expression. 22105995_2 these results indicated that mir-19a and mir-19b likely regulate the expression of tlr2 at the trans-lational level. 22105995_3 taken together, these data demonstrated that the tlr2 regulation by mir-19a and -19b has an effect on il-6 and mmp3 release by blp-activated ra fls. 22105995_4 altogether, these data suggested that tlr2 mrna is a direct targetfor posttranscriptional regulation by mir-19a and mir-19b. 16822819_1 two specific mirnas, mir-197 and mir-346, are significantly overexpressed in ftc. in vitro overexpression of either mirna induces proliferation, whereas inhibition leads to growth arrest. 23450709_1 mir-30a, but not mir-30b/c/d/e, could specifically bind the 3'utr of lyn in b cell lines. 23450709_2 meanwhile, overexpression of mir-30a could inhibit the level of lyn and consequently plays an important role in b cell hyperactivity in patient with sle. 24529171_2 taken together, these data strongly suggest that e2f5 was a direct target of mir-181a. 26540633_1 taken together, we conclude that the transcription factor e2f1 is responsible for the activation of sphk1 promoter elevated by hulc. 26540633_2 thus, we conclude that hulc is able to up-regulate e2f1 by sequestering mir-107. 26344648_1 these data suggest that mir-21 targets bcl-2 mrna to suppress its translation. 26344648_2 together, we showed that grh2 may induce apoptosis of leukemia cells through mir-21-modulated suppression of bcl-2 . 25896250_1 through examining the effect of ppar-alpha on fatty liver development, we found that ppar-alpha is a target of mir-17-5p. 25896250_2 mir-17-5p was found to repress ppar-alpha expression, while ppar-alpha could bind to the promoter of mir-17 and increase its transcription, forming a feedback loop in the regulation of steatosis and fatty liver development. 25896250_3 in our study, ectopic expression of mature mirna-17-5p significantly reduced expression of ppar-alpha through targeting ppar-alpha 3'-utr . 20713703_1 meis2 gene is a direct target of mir-204. in addition, point mutations in the mir-204 binding site of the meis2 3'-utr abolished this repression, indicating that mir-204 directly and specifically target meis2 . in agreement with these observations, the levels of meis2 protein in h36ce human lens epithelial cells were decreased in the presence of mir-204 duplexes and elevated on mir-204 inhibition . 20713703_2 moreover, injections of mir-204 duplexes resulted in a decrease in endogenous meis2 mrna and protein levels, whereas injections of mo-mir-204 led to an increase in the optic cup of medakaembryos . 20713703_3 altogether, these data strongly indicate that meis2 is a bona fide mir-204 target altogether, these data indicate that mir-204 controls lens cell differentiation by modulating the expression of lens placode differentiation genes via the meis2/pax6 pathway. 26517683_1 bmi1 is a reported mir-200 target gene , and increased bmi1 expression has been associated with poor prognosis in bladder cancer patients . 26517683_2 when we determined the bmi1 protein levels according the relative expression of mir-200 family members, we observed that the cluster 2 of mir-200 showed a negative correlation with the protein levels of bmi1, in agreement with the mechanism previously proposed by cao et al. . 26517683_3 we found that bc samples characterized by increased ezh2 expression displayed reduced levels of mir-200c and mir-141 . 26517683_4 these results suggest that bmi1 is able to repress the expression of, at least, some mir200 family members. 26517683_5 collectively, these results indicated that ezh2 activity negatively controls the mir200 family expression in bladder cancer. 22446693_1 brain-derived neurotrophic factor is normally repressed by a conserved noncoding antisense rna transcript, bdnf-as. 22446693_2 as one example, we show that brain-derived neurotrophic factor is under the control of a conserved noncoding antisense rna transcript, bdnf-as, both in vitro and in vivo. 22446693_3 these findings correspond with the in vitro data described above and indicate that the blockade of bdnf-as results in the increase of bdnf mrna and protein expression in vivo. 22446693_4 these findings demonstrate that bdnf-as regulates bdnf levels in vivo. 22446693_5 removal or inhibition of bdnf-as could lead to the locus-specific upregulation of bdnf mrna and protein. 26878986_2 our findings provided the evidences that mir-132 and 223 are critical mediators in positive circuit for pathogenesis of ibd by negatively regulating foxo3a to enhance the expression of inflammatory cytokines and can be a good therapeutic target for ibd treatment. 26878986_3 through bioinfomatic and biochemical analysis, we found that mir-132 and 223 directly regulate foxo3a expression by interaction with 3'-utr of foxo3a. 26878986_4 these data suggest that mir-132 and mir-223 can synergistically regulate foxo3a expression at post-transcriptional level by targeting 3'-utr sequences and it is very specific process for triggering intestinal inflammation. 22072420_1 the binding activity of mir-200b to both smad2 and snail was examined using a luciferase assay. 22072420_2 mir-200b directly targeted smad2 and snail at both cellular and molecular levels. 22072420_4 the expression levels of smad2 and snail were dramatically reduced compared to control after mir-200b overexpression , whereas e-cadherin expression was up-regulated . 18660546_2 the predicted mir-146a target genes include brca1 and brca2, which are key breast and ovarian cancer genes. 18660546_4 breast cancer patients who had at least one mir-146a variant allele were diagnosed at an earlier age than with no variant alleles and ovarian cancer patients who had at least one mir-146a variant allele were diagnosed younger than women without any variant allele . in a target in vitro assay we observed that mir-146a could bind to the 3'utrs of brca1 and brca2 mrnas and potentially modulate their mrna expression. 18660546_5 intriguingly, the binding capacity between the 3'utr of brca1 and mir-146a were statistically significantly stronger in variant c-allele than those in common g-allele . 18660546_6 taken together, our data suggest that breast/ovarian cancer patients with variant c-allele mir-146a may have high levels of mature mir-146 and that these variants predispose them to an earlier age of onset of familial breast and ovarian cancer./r/n 21288303_1 our data also demonstrates that mir-9 target and regulates sirt1 expression in insulin-secreting cells. in mice, mir-9 is expressed from chromosomes 3, 13 and 7, and its precursors are denoted as pre-mir-9-1, pre-mir-9-2 and pre-mir-9-3, respectively, to indicate the loci from which they originate. 21288303_2 to confirm this targeting, the mir-9 binding site in sirt1 3'-utr was mutated and used in the luciferase assay. 21288303_4 these results clearly show that mir-9 specifically target the 3'-utr of sirt1. 21288303_6 importantly, this provides mechanistic insight into the regulation of sirt1 protein in insulin-secreting -beta-cells brought about by mir-9. 22962609_2 to further confirm kif3b modulation by mir-127, kif3b 3'-utr was cloned into luciferase vectors and mrna destabilization assays were carried out. 22962609_3 therefore, kif3b is a real target of mir-127 in our system. 22962609_4 mir-127 overexpression significantly reduces luciferase activity in a dose-dependent manner, demonstrating that this mirna directly regulates kif3b expression. 26687302_2 thus, mir-144-3p targeted mtor and negatively regulated its expression in saccs. 26687302_3 thus mir-144-3p directly binds to the 3 ' -utr of mtor mrna. 26687302_4 we report that overexpression of mir-144 decreased mtor protein expression in adcc cell lines and immunofluorescence confirmed that mtor expression can be downregulated by mir-144 in saccs 19179606_1 the use of the let-7a inhibitor markedly reduced the inhibition by the 3'-utrs of hmga2 , suggesting that the let-7 family down-regulates the expression of hmga2. 19179606_2 to determine the inhibitory effect of the let-7 micrornas on hmga proteins and kras, the let-7a inhibitor was introduced into aspc1 and panc1 cells . 19179606_4 the amount of hmga1 and kras was not significantly affected by the let-7a inhibitor. 19179606_5 these data suggest that let-7 family dominantly targets hmga2 transcripts in pancreatic cancer cells. 23554908_1 in contrast, the mir-215 inhibitor markedly upregulated ctnnbip1 protein levels. 23554908_2 interestingly, ctnnbip1 protein was not altered in the mir-192 mimic- or inhibitor-treated mmcs compared with the control group . 23554908_3 these results indicate that mir-215, but not mir-192, targets endogenous ctnnbip1 in mmcs. 23554908_4 next, we further verified whether ctnnbip1 is a direct mir-215 target using luciferase reporter assays. 23554908_6 3g, the mir-215 mimic significantly inhibited ctnnbip1 3'-utr luciferase activity by 90% relative to the negative mir-control but did not inhibit the two control constructs without the 3'-utr or the mut-ctnnbip1 3'-utr . 21368580_1 we have identified ckap2, lasp1, birc5, wasf1, asap1 and runx2 as new mir-203 direct targetmrnas involved in these events. 21368580_4 relative luciferase activity, quantified 24 h after the co-transfection of reporter constructs and a mir-203 expression vector, demonstrated that mir-203 repressed luciferase activity controlled by the 3'utrs of the six targetmrnas . 21368580_5 figure 5. ckap2, lasp1, birc5, wasf1, asap1, runx2 are direct mir-203 target. 26732596_1 kirsten rat sarcoma viral oncogene which is involved in erk pathway was directly targeted by mir-126 in glioma through binding to two sites in the 3- untranslated region of kras mrna. 26732596_2 moreover, the up-regulation of mir-126 contributes to the aberrant activation of the erk signaling and inhibits cell proliferation and invasion through targeting kras. 26732596_3 these results indicated that mir-126 repressed the erk pathway through targeting and inhibiting kras. 26732596_4 the above evidence suggested that kras is directly targeted by mir-126 and take part in the suppressive of mir-126-inhibition proliferation and invasion. 19239885_1 recently, it was found that the h19 rna is host to an exonic microrna, mir-675, which, as a result, is also imprinted and maternally expressed. 26087886_1 through searching in bioinformatics databases, we identified a highly conserved consequential pairing between il-15 and mir-15b. 26087886_3 in this study, we explored the downstream target of mir-15b in experimental autoimmune myasthenia gravis mice and demonstrated that mir-15b can directly target 3'-utr of il-15 and regulate its expression. 26087886_4 therefore, these results suggest that mir-15b can modulate il-15 expression. 26087886_5 these results thus confirmed the direct binding and regulating role of mir-15b in il-15 expression. 26087886_6 these results prove that mir-15b can directly target il-15 and regulate its expression in eamg mice. 26771839_1 our study further demonstrates that mirna-29a functions as a tumor suppressor which targets c-myc. 26771839_2 our study indicates that mirna-29a is a tumor suppressor that plays an important role during prima-1 met -induced apoptotic signaling by targeting c-myc and provides the basis for novel therapeutic strategies using mirna-29a mimics combined with prima-1 met in mm. on the other hand, luciferase activity of the mutant 3'-utr clone of c-myc did not show any change in the presence of mirna-29a further confirming c-myc as a direct target of this mirna . 12434020_1 mir-15 and mir-16 are located at chromosome 13q14, a region deleted in more than half of b cell chronic lymphocytic leukemia s . 12434020_2 detailed deletion and expression analysis shows that mir-15 and mir-16 are located within a 30-kb region of loss in cll, and that both genes are deleted or down-regulated in the majority of cll cases. 23940701_1 moreover, ef24 treatment also increased pdcd4 and pten expression at the protein level, but not that of bcl2 . 23940701_3 taken together, these results show that mir-21 and mir-21-target genes are affected by ef24 treatment. 23940701_4 upon necropsy, while mir-21 expression was markedly diminished in lung tumor tissue from ef24-treated mice, the expression of mir-21 target genes was enhanced . 9923855_1 1 ahif is a natural antisense transcript derived from hif1alpha gene sequences encoding the 3' untranslated region of hif1alpha mrna; 2 ahif is specifically overexpressed in all nonpapillary clear-cell renal carcinomas examined, but not in the papillary renal carcinomas examined; 3 ahif is overexpressed in an established nonpapillary renal carcinoma cell line under both normoxic and hypoxic conditions; and 4 although ahif is not further induced by hypoxia in nonpapillary disease, it can be induced in lymphocytes where there is a concomitant decrease in hif1alpha mrna. 26036346_1 our in vitro and in vivo experiments indicate that mir-29a and mir-330-5p are strong inhibitors of muc1 expression in pancreatic cancer cells through direct binding to muc1 3'-utr. 26036346_3 mir-29a and mir-330-5p are also deregulated in human pancreatic cancer cell lines and tissues and in pancreatic tissues of kras mice. 26036346_4 we have identified mir-29a and mir-330-5p as two new tumor suppressive mirnas that inhibit the expression of muc1 oncogenic mucin in pancreatic cancer cells. 26287733_1 in this report, we evaluate the role of the mir-34 family members in the regulation of axl in rcc and show that in vitro both mir-34a and mir-34c regulate axl expression through direct binding to the axl 3'utr. 26287733_2 these results indicate that both mir-34a and mir-34c interact with the 3'utr of axl mrna. 26287733_3 using a luciferase reporter assay we confirmed that both mir-34a and mir-34c bind directly to the seed sequence in the 3'utr of the axl mrna transcript. 26082129_1 we found that igfbp3 expression was directly regulated by mir-21 expression in luciferase reporter assays driven by wild-type and mutant 3 ' utr of igfbp3, indicating that igfbp3 is a true mir-21 target gene. 26082129_2 igfbp3 as a mir-21 target gene. 26082129_3 our overall findings suggest that mir-21 promotes tumori-genesis through suppressing the expression of the tumor suppressors, igfbp3 and fbx011. 26747895_1 furthermore, we demonstrate that mir-892b attenuated nf-kappab signaling by directly targeting and suppressing multiple mediators of nf-kappab, including traf2, tak1, and tab3, and thus, mir-892b silencing in breast cancer cells sustains nf-kappab activity. 22614013_1 all these data suggest that mir-26b regulates directly pten expression levels while mir-128 regulates directly bmi1 expression levels in pituitary tumor cells. 22614013_2 mir-26b increased levels suppressed directly pten expression while mir-128 low levels resulted in the up-regulation of its direct target bmi1. 23740209_1 mir-98 target sites in igf-1 were confirmed by luciferase assay in hek293 cells. 23740209_2 these results suggested that mir-98 inhibits igf-1 expression posttranscriptionally. 23740209_3 here, we demonstrated that mir-98 inhibited igf-1 translation in vitro and increased a-beta formation and tau phosphorylation by down-regulating igf-1. 22267008_5 taken together, our findings suggest that the phenotypes of gastric cancer cells are at least partly the result of mir-21 regulation of pten. 17721077_1 the genes for microrna 221 and microrna 222 occupy adjacent sites on the x chromosome; their expression appears to be coregulated and they also appear to have the same targetspecificity. 17721077_2 antagonism of either microrna 221 or 222 in glioblastoma cells also caused an increase in p27 levels and enhanced expression of the luciferase reporter gene fused to the p27 3'utr. 26215676_2 d. a luciferase assay result indicating that tac1 is a direct target of mir-137. 20557304_1 to observe the direct effect of rno-let-7d on lgals3-3'-utr, rno-let-7d expressional plasmid was constructed and the validity was observed in cbrh-7919 cells and pc12l cells . 26310391_1 here, we report that mir-124 suppresses expression of uhrf1 to affect the progression of human bladder cancer through competitive binding the same region of its 3'-utr. 26310391_2 taken together, we here demonstrated that mir-124 can target uhrf1 transcription, potentially contributing to the down-regulation of uhrf1 expression. in this study, we first used the bioinformatics analysis and luciferase reporter system to confirm that mir-124 directly targets the 3'-utr of uhrf1. 26920049_1 among the shortlisted candidates, the autophagy-related gene ulk2 showed two well-conserved mir-26b binding sites with high binding scores in its 3'utr ; therefore we selected ulk2 for further validation. 26920049_2 the alignment of mir-26b with its putative target sequences in the human ulk2 3'-utr is depicted in fig.2a. 26920049_3 treatment of pc-3 and c4-2 cells with mir-26b significantly decreased the ulk2 mrna and protein levels. 26920049_4 taken together, mir-26b down-regulates ulk2 expression in pca cells. 26171207_4 however, in analyses of the er-positive patients, dnmt3a showed significantly higher expression in the mir-29b low expression compared to the high expression group. 26171207_5 mir-29b was induced by gata3 and inhibited metastasis by targeting various genes involved in modifying the tumor microenvironment. 26171207_6 the direct interactions between mir-29b and tet1, tdg and dnmt3a were confirmed by luciferase assays and western blot analysis . 26171207_7 although there are numerous pathways that regulate the levels of tet1 , tdg and dnmt3a in breast cancer, significant inverse correlations were identified between the expression levels of mir-29b and dnmt3a in er-positive patients. 24899173_1 in contrast, bzlf1 and brlf1 expression in ags-ebv cells transfected with a mir-bart20-5p inhibitor was enhanced. 22095284_1 mir-6/11 functions through regulation of the proapoptotic genes, reaper , head involution defective , grim and sickle . 26045996_1 the result of the analysis showed that stat5a is one of the predicted targeting genes and that there is a mirna-1469 binding site at nucleotides 226-232 of stat5a-3'-utr . 26045996_3 these results suggest that mirna-1469 down-regulates stat5a expression by directly targeting its 3'-utr. 22028325_1 this negative effect was mediated by a single mir-194-complementary site in the thbs1 3'-utr, and its elimination resulted in tsp-1 reactivation, impaired angiogenesis in matrigel plugs, and reduced growth of hct116 xenografts. 22028325_2 mir-194 is a direct regulator of thbs1 3'-utr. 22028325_3 these results validated the predicted mir-194 seed sequence in the thbs1 3'-utr. 21968601_2 above results suggest that mir-146a target the predicted site in the smad4 gene. 21968601_3 because the levels of endogenous mir-146a of fibroblasts are low, the mir-146a inhibitors decreased the mir-146a expression insignificantly and its effects on smad4 protein expression are not obvious. 21968601_4 above data suggest that mir-146a might downregulated the targetgene smad4 through inhibition of translation. 21968601_5 overall, these results suggest that overexpression of mir-146a can attenuates tgfb1-induced a-sma protein expression by targeting smad4. 21175428_1 our results show reduced expression of mir-30c and mir-301a, but not of mir-99a, in response to plgf, which have evolutionarily conserved binding sites in the 3'-utr of pai-1 mrna. 21175428_2 these results showed that endogenously expressed plgf regulated basal expression of mir-30c and mir-301a in endothelial cells. 21175428_3 these results indicated that mir-30c and mir-301a, but not mir-99a, likely regulated endogenous levels of pai-1 mrna in hpmvec. 21175428_4 taken together, these data showed that mir-30c and mir-301a, but not mir-99a, were involved in regulation of basal and plgf-induced pai-1 mrna expression. 21175428_5 furthermore, these data indicated that plgf-mediated reduction in the levels of mir-30c and mir-301a resulted in the accumulation of pai-1 mrna through a reduction in its degradation in hpmvec. 21175428_6 therefore, mir-30c and mir-301a, but not mir-99a, are jointly responsible for post-transcriptional inhibition of pai-1 expression. 21175428_7 taken together; these data indicated that mir-30c and mir-301a directly target the 3- utr of pai-1 mrna for turnover, subsequently resulting in downregulation of pai-1 expression. 22042811_1 luciferase reporter gene experiments in human kidney cells confirmed the predicted binding of hsa-let-7c to the 3' untranslated region of nr4a2 mrna. 21285396_1 mechanistically, mir-33 target rip140 mrna by recognizing its targetlocated in a highly conserved sequence of the 3'-untranslated region of rip140 mrna. 21285396_2 these results confirm that mir-33, indeed, acts by targeting the conserved 3'-utr of rip140 mrna to suppress its expression. 21285396_3 together, these experiments identify rip140 as a target of mir-33, and delineate the mechanism of cholesterol action in elevating rip140 expression, which is mediated by down-regulating mir-33 that target the 3'-utr of rip140 mrna. 26549232_1 we provide experimental evidences showing that mir-146a negatively regulates merlin protein levels through its interaction with an evolutionary conserved sequence in the 3 'untranslated region of the nf2 mrna. 26549232_2 these results show that mir-146a, mir-25, mir-32 and mir-7 negatively regulate endogenous merlin protein levels by targeting the nf2-3 ' utr. 26549232_3 here we show that the tumor suppressor merlin is negatively regulated at the posttranscriptional level by different mirnas including mir-146a, mir-132, mir-25 and mir-7. 26304234_1 mechanistically, we confirmed that il8 was a direct target of mir-203, and found that reduced mir-203 promoted npc cell radioresistance by activating il8/akt signaling. 26304234_2 taken together, these results proved that il8 was a direct target of mir-203 in npc cells. in this study, we proved that il8 is a direct target of mir-203 in npc cells, which is for first time reported il8 as a mir-203 target in tumor cells. 26341629_1 in summary, these results showed that keap1 was a direct target of mir-200a in escc cells. 26889813_1 furthermore, the over-expressing mir-218 in glioma cells results in the downregulation of robo1 and upregulation of slit2. 26889813_2 using luciferase reporter assays, we found that robo1 was a direct downstream target of mir-218. 26889813_3 fig. 3. robo1 is a direct target of mir-218. 26889813_4 collectively, this experiment demonstrated that robo1 could be a direct target of mir-218 . 20354188_3 these results indicate that a reduction of socs1 expression can mimic mir-155 in promoting breast cancer cells to proliferate and form soft agar foci, suggesting that targeting socs1 may be a mechanism of the oncogenic function of mir-155 in breast cancer cells. 20354188_4 these results show that socs1 is a direct target of mir-155 in breast cancer cells and that mrna degradation is involved in mir-155-搒uppressing socs1. 20354188_5 these results indicate that the a24g mutation impairs mir-155 binding to the mir-155 binding site of socs1 3'-utr and, consequently, abolishes mir-155 regulation. 26825578_2 reporter assays in hek293t cells revealed mir-490-dependent repression of this 3'-utr, and the single mutationor double mutation partially or completely abolished therepression by mir-490, indicating that mir-490 speci铿乧allytargeted the binding sites in the hnrnpa1 3'-utr. 26825578_3 these results suggest that hnrnpa1 is a direct mir-490target in gc cells. 25494962_1 it was shown that there was increased mir-26a accompanied with downregulated ezh2 expression in the hcc specimens, and ezh2 mrna levels were inversely correlated with mir-26a expression. in addition, the mir-26a mimic transfection decreased the ezh2 expression level significantly in the transfected hepg2 cells and inhibited hepg2 cell proliferation and invasion effectively. 25494962_2 our results indicate that mir-26a exerts growth inhibition in hcc and that its inhibitory effect is mediated briefly by blocking ezh2 expression. 25494962_3 ezh2 was downregulated and inversely correlated with mir-26a levels in hcc specimens post-ifn-a treatment 20224724_1 mir-375 enhances palmitate-induced lipoapoptosis in insulin-secreting nit-1 cells by repressing myotrophin protein expression. 22043014_1 targetscan analysis of the mouse roquin 3- utr revealed a potential target site for mmu-mir-223. 22043014_2 this was confirmed by luciferase reporter assays, which demonstrated that the 3- utr of the roquin gene was a target for mir-223, as seen by the negative regulatory effects . of these, it was particularly interesting that mir-223 expression was elevated in the colon of both il-10 mice and dss-treated mice given the relationship of that mirna to roquin and il-17 expression as described above. 21556765_1 our findings show that rs1434536 in the 3'utr of bmpr1b gene affects thebinding ability of mir-125b to bmpr1b mrna and contributes to the geneticpredisposition to localized prostate cancer and patients aged>70 years. 21556765_2 as smaller values indicate stronger mirna binding, it suggested that replacing c allele by t allele reduced binding ability of mir-125b to bmpr1b mrna. it was confirmed by our further dual-luciferase reporter assay. 21536793_1 a dual luciferase assay confirmed binding of mir-203 to the putative targetbinding site of the socs3 3' untranslated region. 21536793_4 the results support the concept that suppression of socs3 mrna levels by p. gingivalis is mediated by mir-203. 21536793_5 these results establish direct binding of mir-203 to the 3'-utr of socs3. 26402323_1 fig. 4. mir-101 targets 3'-utr of sox9 mrna to inhibit its expression in mouse lung. 26402323_2 the luciferase activities in these cells suggest that mir-101 targets 3'-utr of sox9 mrna to inhibit its expression . 25724519_1 transfection of mir-137/197 resulted in reduction of mcl-1 protein expression, as well as alteration of apoptosis-related genes, and induction of apoptosis, inhibition of viability, colony formation, and migration in mm cells. 25724519_2 mcl-1 was further validated as a direct target of mir-137/197. 25724519_3 conversely, overexpression of mcl-1 partially reverted the effect of mir-137/197. 26787495_1 in this study the snp rs56109847 was identified to be linked with the diarrhea phenotype of ibs in the south chinese han female population, and the functional variant of htr3e3'-utr could inhibit the binding of mir-510 to htr3e 3'-utr. 23804233_1 microrna-23a modulates tumor necrosis factor-alpha-induced osteoblasts apoptosis by directly targeting fas.mechanistic studies showed that microrna-23a inhibits fas expression through a microrna-23a-binding site within the 3'- untranslational region of fas. 26057453_2 data suggested that mir-144-5p bound directly to specific sites in the 3 0 -utr of ccne1, ccne2, cdc25a, and pkmyt1 mrnas. 20417621_1 in this study, we used a high-through- put luciferase reporter screen to demonstrate that p53 can be regulated by microrna-1285 . 20417621_2 notably, mir-612, which has the same seed sequence as mir-1285, cannot bindto the 3' untranslated region of p53. 20417621_3 these findings suggest that mir-1285 can regulate p53 expression by directly binding two targetsites in the 3' utr. 20417621_4 taken together, these results indicate that mir-1285 can reduce the expression level of p53. 26106283_1 collectively, these results indicate that xiap may be a direct target of mir-24 in lscc. 26106283_2 therefore, the increased xiap mrna expression in lscc tissues correlates with low-level mir-24 expression. 26729198_1 our study provided evidence that mir-204 may suppress the metastasis and invasion of gc cells through the regulation of the emt process by targeting snai1. 26729198_2 the results revealed that mir-204 managed to inhibit the expression of snai1 by binding to its 3'-utr site. 26729198_3 additionally, this study enabled us to identify that mir-204 inhibits gc cell metastasis and emt progression by directly targeting snai1. 25501825_1 transient and stable overexpression of mir-660 using mirna mimics reduced migration, invasion, and proliferation properties and increased apoptosis in p53 wild-type lung cancer cells.we 22387590_1 we found a binding site for mir-24 in the 3'utr of human sting. 22387590_2 to examine whether rat sting 3'utr can be directly targeted by mir-24, the entire wild-type 3'utr of rat sting or the mutant 3'utr with a 7 bp mutation in the seed region was cloned downstream of the luciferase gene.consistent 22387590_3 with these data, cotransfection of mir-24 mimics with the mutant reporter did not result in obvious decrease in luciferase activity , indicating that the predicted site is a direct target of mir-24 and it is solely responsible for mir-24 targeting of the rat sting 3'utr. 24646523_2 increased mir-499 level favored survival, while decreased mir-499 level favored apoptosis. 24646523_3 we identified three proapoptotic protein-coding genes-pdcd4, pacs2, and dyrk2-as targets of mir-499. 24646523_4 mir-499 inhibited cardiomyocyte apoptosis through its suppressive effect on pdcd4 and pacs2 expression, thereby blocking bid expression and bid mitochondrial translocation. 21976504_2 additional in vitro studies demonstrated that mir-34c reduces the responsiveness of cells to crf in neuronal cells endogenously expressing crfr1. 23322774_1 these results suggest that mir-31 negatively regulates rasa1. 23322774_2 these results suggest that mir-31 regulates rasa1 expression via a post-transcriptional mechanism only, rather than by affecting its mrna stability. 23322774_3 these results unequivocally demonstrate that mir-31 directly recognizes the 3'-utr of the rasa1 transcript. 23322774_5 therefore, modulation of the rasa1 protein level by mir-31 partially explains why down-regulation of mir-31 promotes cell proliferation. 23322774_6 as a conclusion, in studying the potential mechanisms of mirna action in colorectal cancer, we identified rasa1 as a target of mir-31 by bioinformatics analysis and binding assays, confirming that it is indeed down-regulated by mir-31. 26875895_1 to investigate the exact molecular mechanism of mir-874 in crc, we searched the miranda database and found that mir-874 can potentially target stat3 .western 26875895_3 data in dicates that stat3 is targeted by mir-874. 26875895_4 these results suggested that stat3 inhibition recapitulated the cell phenotype of mir-874 overexpression and indicated that stat3 is a functional target of mir-874. 21795284_1 bantam induces cell proliferation and we have identified the actin regulator enabled as a new target of bantam. 21795284_2 bantam mirna regulates g1-s transition and we have identified the actin regulator enabled as a new target of bantam. 21795284_3 these results indicate that ena is a direct target of bantam in wing disc cells. 21795284_4 we have identified ena, a regulator of actin elongation, as a direct target of bantam that is involved in dv boundary formation. 26650737_3 these results suggested that fgf2 is a direct target gene of mir-195. in this study, fgf2 was confirmed as a direct target gene of mir-195 through luciferase assay and western blot analysis. 25433215_1 targets affected by mir-181a antagomir administered after stroke onset include bcl2 and x-linked inhibitor of apoptosis protein . 26730174_1 in addition, hsa-mir-25, hsa-mir-18a, and hsa-mir-20a shared the common target \bcl2l11; hsa-let-7b and hsa-mir-125b targeted the genes cdc25a, cdk6, and lin28a. 26730174_2 notably, hsa-mir-20a, hsa-mir-18a, and hsa-mir-25 shared the common target gene bcl2l11; hsa-mir-125b, hsa-mir-7a, and hsa-mir-7b cotargeted the gene lin28a. 26730174_3 as presented in this network, the predominant correlated mirna interactions were hsa-let-7b and hsa-mir-125b ; and hsa-mir-18a, hsa-mir-20a, and hsa-mir-25 . 20480203_2 with our experimental approach we revealed that loss of expression of a microrna represents the starting point for a signaling cascade finally resulting in overexpression of bmp4 in melanoma cells. in detail, strongly reduced expression of the microrna mir-196a in melanoma cells compared to healthy melanocytes leads to enhanced hox-b7 mrna and protein levels, which subsequently raise ets-1 activity by inducing basic fibroblast growth factor . ets-1 finally accounts for induction of bmp4 expression. 21242194_1 fluorescence reporter assays showed a direct interaction between mir-20a and the bnip2 3'utr. in contrast, mutation of the mir-20a targetsite restored egfp expression to near control levels , indicating that binding of mir-20a to the bnip2 3'-utr was necessary and sufficient to inhibit egfp expression. 21242194_3 4, transfection of sw620 cells with mir-20a aso resulted in an increased expression of bnip2 mrna and bnip2 protein, while mir-20a overexpression in sw480 cells led to the opposite effect. 21242194_4 altogether, these results demonstrated that endogenous bnip2 is under the regulation of mir-20a, and that bnip2 is a functional mir-20a targetin colorectal adenocarcinoma cancer. 26662405_1 further, zeb2 was confirmed as a direct target of mir-215 by using a luciferase reporter assay. 26194885_1 these results suggest that mir-126a-3p directly binds to the seed sequence in the 3'-utr region of itga11. 26194885_2 transfection of mir-126a-3p mimics led to a decrease in the expression of itga11 mrna and protein in hek293t cells, and transfection of inhibitor led to an increase in the expression of itga11 mrna and protein . 26194885_3 confirming that itga11 was a target gene of mir-126a-3p, and mir-126a-3p could regulate the itga11 mrna and protein. 26155940_1 to further elucidate the relationship between mir-29b and bcl2l2 in gbm, we performed co-transfection reporter assays and determined that mir-29b downregulates bcl2l2 expression by directly binding its 3'-utr. 26155940_2 in this study, we demonstrate that bcl2l2 is an oncogenic, mir-29b target gene and is upregulated in the mesenchymal subtype of gbm. 26155940_3 these analyses revealed an inverse correlation between mir-29b expression and bcl2l2 mrna or protein level, supporting the notion that bcl2l2 is a target of mir-29b. 26155940_4 these data demonstrate that mir-29b directly binds the 3'-utr of bcl2l2 and inhibits protein and mrna expression through sequence-specific mrna cleavage . 24218283_3 repressed by mir-451, pge2 and ccnd1 reversed the inhibitory effects of mir-451 on proliferation. in conclusion, mir-451 played a tumor-suppressing role through modulating the expression of pge2 and ccnd1, suggesting a novel target for the diagnosis and treatment of osteosarcoma. 25881295_1 platelet mir-223 promotes a549 cells invasion via targeting epb41l3. in conclusion, our results demonstrated that mir-223 directly binds to the 3'-utr of the epb41l3 mrna transcript and inhibits epb41l3 translation. 26170849_1 these results indicated that mir-490-5p targeted c-fos and negatively regulated its expression in bladder cancer. 22541023_1 mir-128a was found to regulate the target genes involved in the regulation of adipogenic-, osteogenic- and myogenic genes that include: ppargamma, runx1, and pax3. 22541023_2 ppargamma, runx1, and pax3 were identified as direct targets of mir-128a, and were found to increase in expression following continuous culture of sp cells in vitro as mir-128a expression diminished. 22541023_3 these findings are in agreement with qpcr results showing that the 3'-utrs ppargamma, runx1, and pax3 have mir-128a binding sites and the modulation of these genes may influence sp cell differentiation. 22541023_4 in conclusion, we have identified mir-128a as highly expressed in sp cells and a possible regulator of the cell lineage differentiation through targeting of ppargamma, runx1, and pax3. 21283757_1 regulation of p21 gene expression by mir-106b was assessed by 3' utr luciferase reporter assays and transfection of specific mirna mimics. 21283757_2 furthermore, mutations in both mir-106b targetregions resulted in a 57% increase in luciferase activity, suggesting that both binding sites mediate mirna inhibition of basal p21 expression in cancer cells. 21283757_3 furthermore, the luciferase activity of hct-116 cells transfected with the chimeric vector containing both mutant mir-106b targetsites was not altered with butyrate treatment or with butyrate in the presence of exogenous mir-106b. 21283757_4 figure 2 butyrate-induced p21 protein expression is inhibited by mir-106b. 23629002_1 these results demonstrate that both pre-mir-205 and mir-205bp/s3 directly targeted e2f1. 23629002_2 as e2f1 and vegf were earlier verified to be targets of mir-205-5p in melanoma and breast cancer cells,22,27 we validated that mir-205bp/s3 suppressed the expression levels of these genes in melanoma. 23629002_3 expectedly, transfection with mir-205bp/s3 suppressed the protein expression levels of e2f1 and vegf; although the effect of mir-205bp/s3 was less potent than that of pre-mir-205 . 23420866_1 we assayed pten levels which is a known target for the mir-106b~25 cluster.21 23420866_2 upon transfection of the mir-106b~25 cluster into 293hek cells, pten protein levels were reduced . 23638671_1 furthermore, the ectopic expression of mir-205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. in this study, we confirmed a target gene of mir-205 to be erbb3 based on the results of the luciferase activity assay using either cmm or hmm cells. 23638671_2 to our knowledge, the current study provides new evidence that mir-203 is a prognostic factor for cmm and that mir-205 functions as a tumour suppressor by targeting erbb3 in both cmm and hmm. 20082846_1 recent studies identified micrornas of the let-7 family as post-transcriptional regulators of hmga2. 20082846_2 several studies have reported the post-transcriptional regulation of hmga2 expression by mirnas of the let-7 family. 26346275_1 we found that hk2 and pkm2, two key glycolytic genes in the warburg effect , were predicted to be targets of mir-199a. 26346275_2 mir-199a regulates hk2 and pkm2, we constructed luciferase reporters by cloning the wild-type 3' utrs of hk2 and pkm2 or their mutant versions downstream of the renilla luciferase cdna in the prl-tk vector. 26346275_3 we found that co-transfection of mir-199a mimics significantly decreased luciferase activity of the reporters in the wild-type but barely affected the reporters in the mutants , suggesting that hk2 and pkm2 are the targets of mir-199a.taken 26346275_4 together, these results support the idea that mir-199a down-regulation is required for hypoxia-activated hk2 and pkm2 expression in hcc cells. 26903137_1 considering these results, we concluded that mir-29 reduced the expression of itgb1 via the direct targeting of the 3'-utr of itgb1. 26903137_2 based on the qrt-pcr results and clinical data, we found that itgb1 was upregulated in gc, whereas the expression of mir-29a was inversely correlated . 23796952_1 overexpressing ccat2 can change the expression of bax , cdc25a , and cdkn2a , and the microrna targets such as mir17hg and mir-146a . 22552290_1 functional studies validated cd44 to be a direct target of mir-708 and also identified the serine/threonine kinase akt2 as an additional target together, our findings suggest that reduced mir-708 expression leads to prostate cancer initiation, progression, and development by regulating the expression of cd44 as well as akt2. 22844244_2 we detected modest upregulation of cmyc, e2f3, met and sirt1 in mir-34-deficient mefs, while bcl2 was expressed at similar levels in wild-type and mutant cells . 22844244_3 the upregulation of myc and e2f3 might contribute to the increased proliferation rate we have observed in mir-34 deficient mefs. 24040120_1 these data indicate that vegfr1 and vegfr2 are downstream targets of mir-200. 24040120_2 these data taken together indicate that dclk1 regulates vegfr1 and vegfr2 via mir-200 in pdac. 24939082_1 in the human chondrocytes, the upregulation of mir-146a induced apoptosis, upregulated vegf expression and downregulated smad4 expression. 21271217_1 using human apoptosis rt2 profiler pcr array 384ht, we found that tumor necrosis factor-alpha was up-regulated 12-fold in cells transfected with mir-19a antisense ons compared to the cells treated with the control scramble ons. 21271217_2 mir-19a was predicted to target the 3' untranslated region of tnf-alpha mrna, and this was confirmed by luciferase reporter assay. 26763438_2 thus, we verified that p63 is a target of mir-203 and is regulated by the galectin-7-mir-203 signaling pathway. 26517093_1 by using mouse tumor model, we clearly showed that mir-24 promotes tumor growth and angiogenesis by suppressing bim expression in vivo. 26517093_2 these data demonstrated that mir-24 regulates bim protein levels by directly binding two separated regions in bim 3'-utr. 26517093_3 the following experiments demonstrated that mir-24 directly targets bim in both pac cells and vascular cells, inhibiting cell apoptosis and promoting cell proliferation. 26212040_1 targetscan software found that mir-150 directly binds to mmp14 3'utr. 26212040_3 our results suggested that mmp14 is a target gene of mir-150. . 26212040_4 our study also found that agomir-150 and antagomir-150 can up- or down-regulate, respectively, the mmp14 mrna levels. 26212040_5 the apoptosis results revealed that mmp14 inhibitor group and agomir-150 group had the lowest apoptosis rates compared to the other five groups and no significant difference was found between the mmp14 inhibitor group and agomir-150 group. 26313654_1 compatible with levels of mir-378b, the expression of nkx3.1 decreased at the beginning of differentiation, but increased on the fifth day . 26313654_2 these results show that mir-378b promote epidermal differentiation by targeting nkx3.1 in keratinocytes. 26883496_2 mutating these seed sequences abolished the mir-128-mediated suppression of pcm1 luciferase activity and restored the luciferase activity to the control level , indicating the specificity of mir-128 targeting of the 3'-utr of pcm1. 26883496_3 taken together, these data suggest that mir-128 targets pcm1 expression in npcs, which in turn controls npc proliferation and differentiation in vitro. 26883496_4 taken together, our results suggest that mir-128 is an important regulator of cortical development through pcm1. 26130569_1 antagonism of mir-100 in sk-br-3 cells increased the expression of mtmr3, a target gene of mir-100, which resulted in the activation of p27 and eventually led to g2/m cell-cycle arrest and apoptosis. 26130569_2 this indicated the existence of a direct interaction between mir-100 and mtmr3 mrna. 26130569_3 the data were consistent with the expression profiles in breast cancer cells , suggesting that mtmr3 was a target gene of mir-100 in sk-br-3 cells. 26130569_4 as previously reported20, mir-100 could target the smarca5 gene in mcf7 and hmle cells, in which mir-100 was downregulated. in this context, mir-100 targeted different genes in various breast cancer cells. in sk-br-3 cells, mir-100 inhibited apoptosis by negatively regulating the expression of mtmr3. 26130569_5 this indicated that mir-100 negatively regulated p27 expression by targeting mtmr3, which suggested that the interaction between mir-100 and mtmr3 was associated with cell cycle regulation and apoptosis. 22240256_3 others, such as mir-31 and mir-31*, had no previously reported connection with hiv-1 infection but were found here to differ significantly with uncontrolled hiv-1 replication. 23760605_2 altogether, this demonstrates that wasl is indeed a target of mir-142-3p. 23760605_3 collectively, we demonstrate that: mycobacteria infection of mφs results in a short-lived induction of mir-142-3p, and in the case of mtb, accompanied by a partial decrease of n-wasp protein levels n-wasp mrna is a direct target for mir-142-3p, mir-142-3p leads to a significant decrease of intracellular mycobacteria intake by mφs, and the sirna-mediated inactivation of n-wasp in human mφs affects the initial rate of phagocytosis of mtb. 26678661_2 among the possible radiation sensitivityrelated genes in mg cells, we found that atm, rad51, akt, pld2, src, and jak1 had a high possibility of being target genes of mir-203, as predicted by multiple algorithms. 26678661_4 western blot analysis validated the fact that mir-203 downregulated atm, rad51, src, pld2, pi3k-akt, jak-stat3, vegf, hif-1alpha, and mmp2. 18234899_1 the coordinated application of mirna profiling, affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that mir-107 may be involved in accelerated disease progression through regulation of bace1. 21102440_1 here we show that mir-199b is a direct calcineurin/nfat target gene that increases in expression in mouse and human heart failure, and targets the nuclear nfat kinase dual-specificity tyrosine- -phosphorylation regulated kinase 1a , constituting a pathogenic feed forward mechanism that affects calcineurin-responsive gene expression. 21102440_2 together, these data demonstrate the presence of a functional and evolutionarily conserved mir- 199b seed region in the 3' utr of dyrk1a. 21102440_3 more importantly, we have identified the mechanism by which mir- 199b enhances calcineurin/nfat-mediated pathological cardiac hypertrophy, by active downregulation of its direct target gene, dyrk1a . 24393525_1 in this study, we found that per3 was downregulated in crc tissues and crc cell lines, whereas mir-103 was upregulated in crc cell lines. 23447642_2 furthermore, mir-424/322 overexpression resulted in decreased expression of its predicted targets: cyclin d1 and ca -regulating proteins calumenin and stromal-interacting molecule 1 . 23447642_3 using reporter luciferase assays, we confirmed that cyclin d1 and calumenin mrnas were direct targets of mir-322, whereas mir-322 effect on stim1 was indirect. 23164240_2 the dual luciferase assay suggested that trpv4 was the direct target gene of mir-203. 23164240_3 over-expression of mir-203 inhibited the expression of trpv4 and increased no expression in mccs. 23164240_4 e2 inhibited no expression by inhibition of mir-203, which was concurrent with the up-regulation of trpv4 expression level in mccs. 26056285_2 we reasoned that if the target predictions were reliable, predicted wt-mir-204 targets should be enriched within the genes down-regulated in wt-transfected cells, whereas predicted mut-mir-204 targets should be enriched within the genes down-regulated in mut-transfected cells. 26813459_1 both mir-301a and mir-301b could directly target 3'-utr of ndrg2 and decrease its expression. 26813459_2 mir-301a and mir-301b directly target 3'-utr of ndrg2 and decrease its expression. 26813459_3 through performing dual luciferase assay, we confirmed that both mir-301a and mir-301b could downregulate ndrg2, a prostate tumor suppressive gene. 24481267_2 interestingly, lung cancer cells with lower endogenous mir-153 expression are more sensitive to ectopic overexpressed mir-153. 24481267_3 the ic50 of mir-153 on lung cancer cells is positive correlated with the endogenous mir-153 level, while negative correlated with akt level. 24481267_4 knockdown of akt expression suppressed lung cancer cell proliferation. in summary, mir-153 exerted anti-tumor activity in lung cancer by targeting on akt. the sensitivity of lung cancer cells to mir-153 is determined by its endogenous mir-153 level. 21049046_1 mir-200 family members targetthe transcriptional repressors zeb1 and zeb2. 21049046_2 previous studies showed that inhibition of emt by mir-200 family members was mediated by their inhibition of the expression of the e-cadherin repressors zeb1 and zeb2 through binding to the 3'-utr region of zeb1 and zeb2 mrnas -揫3. in order to confirm that mir-200 family members targetzeb1 and zeb2 3'-utrs, we co-transfected either zeb1-3'-utr-luciferase or zeb2-3'-utr-luciferase reporter vectors with mir-200 family precursors in hk-2 cells. 21049046_3 real time pcr analysis confirmed that zeb1 and zeb2 were induced in a time-dependent manner after obstruction , an effect reversed by injection of mir-200b precursor . 17898713_1 although mir-10b overexpression did not cause degradation of hoxd10 mrna , it did, however, reduce the activity of a luciferase reporter gene fused to the wild-type hoxd10 3' utr , indicating that mir-10b target hoxd10 through translational inhibition. in support of these results, we observed a clear reduction in the level of the endogenous hoxd10 protein in mir-10b overexpressing cells . 21071579_2 further studies on a new mechanism of arhi downregulation showed a significant inverse relationship between arhi and mir-221 and 222, which were upregulated in prostate cancer cell lines. 26301516_1 furthermore, the luciferase reporter assay confirmed that mir-30a directly binds to the predicted 3'-utr target sites of the hspa5 gene. 26301516_2 the results suggest that mir-30a can directly bind to 3'-utr of hspa5 mrna, induce its degradation, and finally downregulate its protein level in primary cultured neurons. 26437572_1 our previous study found that acsl1 may be a target of mir-34a, so here we constructed wild-type and mutant luciferase reporter plasmids according to the predicted rno-mir-34a binding site on the 3'-utr of the acsl1 mrna. 26437572_2 the results indicate that rno-mir-34a specifically binds to the 3'-utr of acsl1. 26437572_3 these findings confirm that acsl1 expression is negatively regulated by rno-mir-34a. 26405762_1 these results indicate that mir-584 could inhibit the expression of rock1, and rock1 knockdown would further affect the migration ability of k1 cells. 26405762_2 indicating that mir-584 can inhibit the expression of rock-1 in k1 cells. 26684241_2 we further identified mir-192 as a metastasis suppressor of hcc and slc39a6, which is an oncogene involved in different types of cancer , as a direct and functional target for mir-192 in hcc. 26684241_3 taken together, these results indicated that slc39a6 was a direct downstream target of mir-192 in hcc cells. 26872365_1 bioinformatics, western blot analysis and luciferase reporter assay demonstrated that fgfr1 is a direct target of mir-214. 26872365_2 taken together, all above supported that mir-214 attenuated osteoblast differentiation via suppression of the fgfr1 downstream pathway. 26872365_3 results revealed that mir-214 regulated the fgfr1 expression by directly targeting the 3'-utr of fgfr1. 26840046_1 mir-133b directly targets sgk1 to reverse the hydrosalpinx-induced down-regulation of hoxa10 and to attenuate the impairment of embryo attachment in vitro. in the present study, we identify mir-133b as an inflammatory microrna that contributes to endometrial receptivity and embryo attachment by suppressing sgk1 expression and increasing hoxa10 expression. 26840046_2 our target analysis demonstrated that sgk1 is a functional target of mir-133b-mediated hoxa10 expression, consistent with a previous report that increased sgk1 activity in the endometrium decreases hoxa10 expression and interferes with embryo implantation . 26695144_2 western blot assay showed that overexpression of mir-494 inhibited igf1r expression and its downstream signal protein expression. in addition, downregulation of igf1r has similar effects with mir-494 overexpression on eoc cells and overexpression of igf1r effectively rescued the inhibition of overexpressed mir-494 in eoc cells. 26695144_3 these data suggested that mir-494 functions as a tumor suppressor in eoc by targeting igf1r. 10814723_1 disc2 apparently specifies a non-coding rna molecule that is antisense to disc1, an arrangement that has been observed at other loci where it is thought that the antisense rna is involved in regulating expression of the sense gene.the 10814723_2 5-and of the transcript has not yet been located, but disc2 so far consists of a single large exon encompassing the translocation breakpoint and the 189 nt exon of disc1. 10814723_5 disc2 transcripts are most abundant in heart where species of >9.5 kb, and of ~6, 3 and 2.5 kb are present . 26718213_1 therefore, the data also demonstrated that sema 4d was the direct target of mir-214 and was negatively regulated by mir-214 in ovarian cancer cells. 26718213_2 therefore, our data also demonstrated that sema 4d was negatively regulated by mir-214 and was the direct target of mir-214 as further proved in luciferase activity assay. 26718213_3 those results suggested that mir-214 negatively regulated sema 4d expression via direct binding to putative sites in the 3'-utr region of sema 4d mrna. 26718213_4 the luciferase assays further demonstrated that mir-214 directly regulated sema 4d mrna expression through the mir-214 binding atthe 3'-utr region of sema 4d mrna in skov-3 cells. 26398880_1 luciferase reporter assay revealed that iq motif containing gtpase activating protein 1 is a direct target of mir-506. 26398880_2 mir-506 regulates iqgap1 expression by directly targeting its 3'utr. in this study, we first identified iqgap1 as a direct target of mir-506. 23936432_1 mir-182 expression in pc3 cells was also increased in response to stress induced by serum withdrawal, suggesting that mir-182 upregulation can occur due to nutritional stress. 23936432_2 bcl2 and p21 were identified to be potential target genes of mir-182 in pc3 cells. 26908446_1 collectively, these results demonstrated that mir-323-3p directly associated with the mrna 3'-utr regions of smad2 and smad3 transcripts, thereby identifying smad2 and smad3 as bona fide targets of mir-323-3p. 21931765_1 here, we show that stable nucleic-acid-lipid particles carrying mature mir-34a can target dll1 in vitro and show equal effects to those of adenovirus mir-34a cell infection. 25184675_1 moreover, we found that three mirna families, mir-20, mir-92, and mir-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein bim. 23928699_1 these findings suggest an undescribed regulatory pathway in cervical cancer, by which oct4 directly induces expression of mir-125b, which inhibits its direct target bak1, leading to suppression of cervical cancer cell apoptosis. 26333874_1 the mir-126- 3p sponge neutralised the downregulatory effects induced by platelet mps on the endogenous atf3, atp1b1, atp9a and rai14 mrna levels , whereas the empty vector, control sponge, did not . 26333874_2 these results support a role for platelet mp-derived mir-126- 3p in regulating atf3, atp1b1, atp9a and rai14 expression at the mrna level. 26055091_1 down-regulation of the targets ywhae, ubb, npm1, and hsp90aa1 by hcmv-mir-us25-1-5p was validated by luciferase reporter assay and western blot analysis. 26055091_3 therefore, these results indicated that hcmv-mir-us25-1-5p repressed these targets via the predicted binding sites. in our study, four host cellular genes were demonstrated to be direct targets of hcmv-mir-us25-1-5p by luciferase assay and western blot. 21730146_1 here we demonstrate that the muscle-specific mirnas mir-1 and mir-206 directly targetpax3. 21730146_2 the patterns suggested a possible role for mir-1/mir-206 in the complete down-regulation of pax3 within the myotome and limb muscle masses, following myoblast commitment. 21730146_3 consistent with this, ectopic expression of mir-206 in the dorsomedial dermomyotome led to localized loss of pax3 . 21730146_4 dual-luciferase assays showed that mir-1 and mir-206 directly targetthe pax3 3'-utr through both predicted targetsites . 21730146_5 thus, antagomir injections and pax3-specific tps resulted in similar phenotypes, indicating that efficient repression of pax3 by mir-1/mir-206 is crucial for timely progression of myogenic differentiation. 26177460_1 thus tp53 is a mir-34a target gene that binds to mir-34a through noncanonical 5'- utr and cds mres. 26177460_2 thus, mir-34a overexpression modulates p53 expression post-transcriptionally, both negatively and positively, via direct targeting of tp53 and indirect enhancement of p53 stability. 26175215_2 consistent with the array, many transcripts are targeted by mir- 140- 5p with galntl1 the most susceptible to overexpression of mir- 140- 5p, while fzd6 and b3gnt1 were upregulated most by inhibition of mir- 140- 5p and therefore the predominant targets of endogenous mir- 140- 5p. to assess which of these candidate genes are directly targeted by mir- 140- 5p, we cloned the 3- untranslated regions of the most regulated candidates for luciferase assays. 26175215_3 we confirmed many as bona fide targets of mir- 140- 5p by mutation of 3'-utr target sites including fzd6, galc, galntl1, mmd, and rala . 22781751_1 dual luciferase reporter assay confirmed that the mirna binding sequences in the 3'utr of ulk1 contribute to the modulation of ulk1 expression by mir-20a and mir-106b.//dual 22781751_2 luciferase reporter assay confirmed that the mirna binding sequences in the 3' utr of ulk1 contribute to the modulation of ulk1 expression by mir-20a and mir-106b.//mir-20a 22781751_3 and mir-106b negatively regulate autophagy induced by leucine deprivation via suppression of ulk1 expression in c2c12 myoblasts.// 22781751_4 we discovered the essential autophagy gene ulk1 as cellular target of mir-20a and mir-106b. 18227515_1 we now show that endothelial cells express microrna 126 , which inhibits vcam-1 expression. 18227515_4 taken together, these data suggest that mir-126 regulates vcam-1 expression through a mir-126-binding site in the vcam-1 3'-utr. 23333058_1 overexpression of mir-17-5p/20a promoted gastric cancer cell cycle progression and inhibited cell apoptosis, whereas knockdown of mir-17-5p/20a resulted in cell cycle arrest and increased apoptosis. 23333058_2 p21 and tumour protein p53-induced nuclear protein 1 were validated as the targets of mir-17-5p/20a. 14962667_2 exonic sequence of a dio3os cdna overlaps with the dio3 promoter and strong promoter activity in the antisense orientation is detected in a genomic fragment located 3' of mouse and human dio3 but not in the dio3 promoter region. 14962667_3 these data showed that at least one other gene, which we have designated in the human and the mouse dio3os and dio3os, respectively ,is transcribed from this locus in an orientation that is antisense to that of dio3 and dio3. 20548023_1 in vivo, transcripts containing the 39 untranslated region of pten, including the mir-214 targetsequence, were negatively regulated after t cell activation, and forced expression of mir-214 in t cells led to increased pro- liferation after stimulation. 20548023_2 at 72 h, levels of pten mrna were decreased in both cd4 and cd8 cells , correlating with an increase in mir-214 and a decrease in pten protein levels . 20548023_3 expression of mir-214 also led to a decrease in pten protein expression in hio80 cells, compared with cells transfected with control plasmid alone , confirming that our lentivirally encoded mir-214 was capable of downregulating pten expression. 20548023_4 these data suggest that upon t cell activation, transcripts containing the 3- utr of pten matching the mir-214 seed sequence are targeted and downregulated. 22879939_1 tgf-beta-stimulated mir-21 target pten 3'utr to inhibit pten expression. 22879939_2 these results suggest that mir-21 target pten in mesangial cells. 22879939_3 our results uncover an essential role of tgf-beta-induced expression of mir-21, which target pten to initiate a non-canonical signaling circuit involving akt/mtorc1 axis for mesangial cell hypertrophy and matrix protein synthesis. 23681145_1 knockdown of mir-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of mir-21, and resulted in significant down-regulation of phosphorylated protein kinase b and increased tubular cell apoptosis. 19881953_1 more importantly, we determined that the ebv latent membrane protein 2a is the putative target of mir-bart22. 19881953_2 lmp2a is a potent immunogenic viral antigen that is recognized by the cytotoxic t cells; down-modulation of lmp2a expression by mir-bart22 may permit escape of ebv-infected cells from host immune surveillance. 19881953_4 our findings emphasize the role of mir-bart22 in modulating lmp2a expression, which may facilitate npc carcinogenesis by evading the host immune response. 25739101_1 mir-377 downregulated tiam1 through interaction with its 3- -untranslated region. 22160687_2 the effect of mir-34a overexpression on syt-i and stx-1a transcripts was confirmed at the protein level because cortical neurons transfected with pre-mir-34a showed a significant reduction in expression of the two proteins after 72 h. 26261072_1 pu.1 is a validated target of mir-155 and has been reported to be downregulated in several lpd subtypes . 26261072_3 we found upregulation of mir-155 and downregulation of its target pu.1 in clinical cases of human lpds: dlbcl, b-cll/sll, hl, mzl and fl. in addition, we found downregulation of pu.1 in mcl in the context of normal mir-155 expression, suggesting that regulation of pu.1 level is more complex in this lymphoma subtype. 26261072_4 our results also suggest a role for pu.1 and mir-155 in the adverse prognosis of b-cll/sll and hl. 25611699_1 down regulation of mir-202 modulates mxd1 and sin3a repressor complexes to induce apoptosis of pancreatic cancer cells. 23665235_1 these results clearly indi-cated that mir-224-5p would directly recognize and bind to the 3'-utr of egr2 and acsl4. 26813676_1 we found that mir-124a directly targets stat3 in luciferase assays using the full-length 3'-utr of stat3 .all 26813676_2 tet-mir-124a leukemic cell lines demonstrated a significant reduction of endogenous stat3 protein levels upon induction of mir-124a . 21077158_1 mir-196a expression plasmid led to strong downregulation of hox-c8 expression in melanoma cells. 21077158_2 different fragments of the hox-c8 3'utr confirmed direct interactions of mir-196a with the hox-c8 mrna. 21077158_3 although the mature sequences of mir-196a-1 and mir-196a-2 are completely identical, we generated both mir-196a-1 and mir- 196a-2 stable transfected cell clones to exclude homologuespecific effects on the targetgene hox-c8. 21077158_4 hence, re-expression of mir-196a in melanoma cells leads to a silencing of transcription factor hox-c8. this points to the presence of additional sequences in the hoxc8 3' utr, which are functionally active in the mir-196a mediated regulation of hox-c8 expression. 26307536_1 among several htt co-expressed genes, mfn2 was shown to be the direct target of mir-214. 26307536_3 this is suggestive of the fact that mir-214 reduces the expression of endogenous mfn2. 26307536_4 fig. 2. mir-214 regulates the expression of mfn2 by targeting 3'utr of the gene. 26307536_5 the results further explain that the mitochondrial and cell cycle changes in hd are due to decreased mfn2 resulting from the increase in mir-214. 26307536_6 thus, we conclude that mir-214 modulates hd pathogenesis via mfn2 apart from a direct involvement by targeting htt. 25576360_1 mir-25 directly targets btg2 and suppresses its expression. 25576360_2 these results thus verified the two mir-25-btg2 interactions and confirmed mir-25 can directly suppress btg2 expression. 23715613_1 computational predictions of mirnas targeting vegf-a of all the mirnas predicted to target vegf-a, mir-150 was selected for further investigation as it was the most downregulated. in view of an interaction between mir-150 and vegf-a mrna with the highest degree of correlation, we evaluated the role of mir-150-mediated regulation of vegf-a gene expression. 25572678_1 in an attempt of characterizing sox4 overexpression mechanism, we identified mir-30a as a tumor suppressor that directly targets sox4 in chondrosarcoma cells. 25572678_2 collectively, our data confirmed that mir-30a negatively regulates sox4 expression by directly targeting its 3'-utr in chondrosarcoma cells. 25572678_3 furthermore, we demonstrated that sox4 acted as an oncogene and was directly regulated by mir-30a in chondrosarcoma cells. 25279428_2 age-induced mir-200b and mir-200c downregulation led to increased expression of their target genes, rhoa and rock, respectively. 26084457_2 as shown in figure 2c, the dmd protein expression level was significantly decreased after 48 hours of transfection,but no significant difference in mrna was detected,suggesting that mir-340 predominantly suppresses dmd translation other than degradation of mrna.10 such results results confirmed dmd to be a direct target gene of mir-340. 26715279_1 overexpression of rock1 mrna and proteins was found in the anti-mir-145 transfected mcf-7 cells compared with the anti-nc-transfected cells . 26715279_2 these results demonstrated that mir-145 may directly target rock1 in breast cancer. 26715279_3 mir-145-mimics inhibited the expression of rock1 at the mrna level in the transfected mcf-7 cells. 26773046_1 subsequent 3' untranslated region luciferase reporter assays confirmed that the translation of both alphaiib and -beta3 mrnas can be regulated by mirnas mir-326, mir-128, mir-331, and mir-500. 26773046_4 mir-331 and mir-500 also repressed reporter gene expression placed under the control of the -beta3 mrna 3'-utr . 9774350_1 oxys rna inhibits fhla translation by pairing with a short sequence overlapping the shine cdalgarno sequence, thereby blocking ribosome binding/translation. 25960238_1 downregulation of mir-206 and upregulation of ccnd2 mrna in human gastric cancer tissues. 25466836_2 ccl2 was a novel target gene of mir-495. 25466836_3 mir-495 significantly promoted huvecs proliferation by altering cell cycle distribution, and it also inhibited huvecs apoptosis by affecting the expression of cleaved caspase 3. effects of mir-495 on huvecs proliferation and apoptosis were significantly reversed by overexpression of ccl2. 26775030_2 this inhibitory effect was lost when the 7bp seed sequence recognition site in the 3'-utr was mutated, thus indicating a direct interaction between mir-322 and these mrnas . 26775030_3 as expected from in vitro and in vivo results the levels of mir-322 targets insr, igf1r and cd1 were significantly decreased in aav322-injected hearts while igf1r, cd1 and sirt4 increased in aavsponge-injected ones . in this study we present for the first time to our knowledge a role for mir-322/424 in regulating heart function in a model of metabolic syndrome and validated new targets insr, igf1r and sirt4 conserved between human and rodents. 22161865_1 mechanistic studies revealed that mir-146a repressed the expression of egfr through binding to its 3'-untranslated region. 22161865_2 to ascertain the direct mirna-targetinteraction, egfr 3'-utr was cloned into luciferase reporter cloning site in the pmir reporter dual luciferase vector. 22161865_3 interestingly, mir-146a repressed egfr expression in both mrna and protein level, and mir-146a also decreased expression of p-erk1/2 protein but not total erk1/2 protein. 20501654_1 we identified vegf-a as a putative target of mir-93 in the kidney with a perfect complementarity between mir-93 and the 3'-untranslated region of vegfa in several species. 20501654_2 as determined by rna hybrid analysis, we also found that mir-93 and its binding site in vegfa could potentially form a very stable secondary structure . 20501654_3 importantly, suppression of the vegfa 3'-utr by mir-93 mimics was abrogated when cells were transfected with mir-93 mutant , consistent with the conclusion that mir-93 acts as a negative regulator of vegfa by binding to the vegfa 3'-utr. 20501654_4 taken together, these results indicate that mir-93 down-regulates vegf expression through binding to the 3-utr of the vegfa gene. 20501654_5 taken together, these results indicate that mir-93 directly down-regulates vegf expression. 18456660_1 met proto-oncogene is a target of mir-199a*. 18456660_2 several lines of evidence indicate that mir-199a* is a putative tumor suppressor: 1. the expression of mir-199a/a* is silenced in all proliferating cell lines tested except fibroblasts. 18456660_4 3. mir-199a* downregulates met proto-oncogene and also downregulates erk2, an effector downstream of met. 26536844_1 a lox 3 ' utr luciferase reporter assay showed that mir-27 directly targeted lox. 26536844_2 taken together, these results suggest a novel role for mir-27 in repressing adipogenic lineage commitment by targeting lox. 26536844_3 these observations strongly support that lox is directly targeted by mir-27a and mir-27b during bmp4-induced c3h10t1/2 cell adipocyte lineage commitment. 25630703_1 interestingly, the glti mrna itself is a target of gcvb , raising the possibility that base-pairing at the ca-rich target site in the glti 5'-utr might contribute to gcvb depletion. 21874051_2 these results clearly demonstrate that mir-128 can directly target egfr and pdgfr-beta by binding to their 3'-utrs and repressing translation . 21874051_3 our results have established that mir-128 can repress mitogenic signaling mediated by egfrviii in ginscs, by targeting egfr and pdgfr-beta. 26854727_1 these results demonstrated that mir-26a-5p binds the seed matched sequence presentin the 3 0 utrof human inos mrna. 26854727_2 taken together, these findings proved that 3 ' utr of inos is involved in the direct suppression of mir-26a-5p via nf-k b activation in il-1 b -stimulated human oa chondrocytes. 26854727_3 we found that inos expression was directly regulated by mir-26a-5p in human oa chondrocytes 26769181_1 finally, dab2 was identified as a mir-106b-directed target gene by dual-luciferase reporter assay. 26769181_2 mir-106b was involved in tgf--beta1-induced cell migration by targeting dab2 in cervical carcinoma. 26769181_3 another important finding from this study was that mir-106b directly targeted the 3'-utr of the dab2 and inhibited dab2 expression as seen on double luciferase reporter gene assay. 22045061_2 two identical potential binding sites were found for mousemir-1 and cx43 . 22045061_3 by comparison, mir-1 produced virtually no effect on cx43 mrna levels , indicating that it does not affect cx43 mrna stability. 22045061_4 fig. 4 post-transcriptional repression of cx43 by mir-1. 25483280_1 lgr5 is a target of mir- 100 in colon cancer cells . 25483280_2 mir-100 downregulated the expression of lgr5 protein by targeting its 3'-utr 22909339_2 the mir-221 overexpression in gc-1 cells reduced the expression level of c-kit by approximately 75%, whereas gc-4 cells displayed no expression of c-kit . 22909339_3 overexpression of mir-34b-5p in gc-1 cells inhibited the expression of cdk6 by 25% and this effect was even more pronounced in gc-4 cells with approximately 55% inhibition in mir-34b-5p-transfected cells compared with the scramble mirna-transfected cells . 23233740_1 the ectopic transfection of double-stranded rna mimicking mir-596 or specific small interfering rna for lgals3bp significantly induced growth inhibition and apoptosis in cell lines lacking mir-596 expression or overexpressing lgals3bp, respectively, in a manner associated with a suppression of erk1/2 phosphorylation. 26417995_1 h19/mir- 675 downregulates the expression of tgf-beta1. 26417995_2 the protein expression of tgf-beta1 was also decreased in h19/mir- 675 overexpressing hmscs and increased in hmscs with h19/mir- 675 downregulation . 22088371_1 introducing exogenous mir-218 may effectively down-regulate the cdk6 expression, inhibit cell proliferation and induce apoptosis of malignant giloma cells. 19131648_1 pp2a regulatory subunit b56alpha is a targetfor silencing by mir-1. 19131648_2 binding of mir-1 to b56alpha encoding rna was confirmed by a luciferase reporter assay . 19131648_3 moreover, the mir-1 targeting of b56alpha in cardiac myocytes was confirmed by quantitative immunoblot analysis using an anti-b56alpha antibody . 17222355_2 this is accompanied by enhanced expression of mirna-98 and other mirnas, which predictably target hmga2. 17222355_3 moreover, transfection of pre-mir-98 during normoxia diminishes hmga2 and potentiates resistance to doxorubicin and cisplatin. 25446261_2 found that up-regulated casc2 decreased the expression of mir-21 significantly and there is a reciprocal repression between casc2 and mir-21 in an argonaute2-dependent manner. 22561557_1 cul5 was identified as a novel targetgene of both mir-19a and mir-19b. 22561557_3 analysis by western blot also showed a reverse correlation between mir-19a/b expression and cul5 protein levels . 22561557_4 thus, we concluded that mir-19a/b facilitates proliferation and invasion by down-regulating cul5 expression in cervical carcinoma cells. 22561557_5 fromthese results, we concluded that mir-19a/b could negatively regulate cul5 expression through direct binding to a unique sequence in the cul5 mrna 3'utr. 21565979_1 combinatorial analyses of the ago2 immunocomplex and gene expression profiles identified p21 as a direct target of mir-22. 21565979_2 these results show that mir-22 controls p21 expression by both inhibition of translation and degradation of mrna. 21565979_3 these observations suggest that mir-22 directly represses p21 expression via a post-transcriptional mechanism. 21565979_4 in summary, the data presented suggest a role for mir-22 as an intrinsic molecular switch in the p53 tumor suppressor network, functioning as a determinant of cell fate at a post-transcriptional level by inducing apoptosis via direct repression of p21. 20406806_1 mir-148a reduced msk1 expression by directly targeting its 3'-utr in pc3pr cells. 20406806_2 msk1 was a direct target of mir-148a in pc3 cells. in all, these results suggest that mir-148a may directly bind to the sites 1 and 3 of the mski 3'-utr and inhibit its protein expression. 20406806_3 collectively, these results indicate that mir-148a attenuates paclitaxel resistance of pc3pr cells through regulating msk1 expression. 21212803_1 these data indicate that mir-31 target the 3'-utr of the dystrophin mrna and that repression is prevented either by the use of mir-31 decoys or by protecting the mir-31 binding site on dystrophin mrna. in all cases dystrophin mrna levels were not affected by mir-31 modulation, indicating that the mirna acts by repressing translation rather than controlling dystrophin mrna stability. 21212803_2 these results indicate that dystrophin increase is mainly due to translational de-repression as a consequence of mir-31 depletion. 21212803_3 the intense and localized expression of mir-31 in regenerating myoblasts of dystrophic muscles indicates that the high levels of mir-31 found in dystrophic conditions-in both mouse and human biopsies-are due to the intensive regeneration programme that is mediated by the activation of satellite cells. 21051724_1 mitf and cdk6 are target of mir-137. 21051724_2 these results demonstrate that mir-137 directly target the mitf and cdk6 through the binding sites on their 3' utr. 21051724_3 western blot analysis showed that mitf was dramatically reduced when cells were transfected with mir-137 . 21051724_4 primary target of mir 137, such as cdk6, were suppressed by transfection with mir-137, as expected . 25299073_1 mir-181b-5p downregulates nova1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma. 24837367_1 we identified that lncrna-bgl3 was a target of mir-17,mir-93, mir-20a, mir-20b, mir-106a and mir-106b, micrornas that repress mrna of phosphatase and tensin homolog . 24837367_2 further experiments demonstrated that lncrna-bgl3 functioned as a competitive endogenous rna for binding these micrornas to cross-regulate pten expression. 26645045_2 accordingly, sp exposure of ncm460-nk-1r cells increased il-6r mrna expression, while overexpression of mir-221-5p reduced il-6r expression. 26645045_3 nf-kappab and jnk inhibition decreased sp-induced mir-221-5p expression. 26645045_4 thus, mir-221-5p inhibits il-6r mrna expression in human colonic epithelial cells. 26645045_5 together, these results indicate that il-6r is a downstream target of mir-221-5p in human colonocytes. 26645045_6 these results indicate that nk-1r-mir-221-5p signaling is activated and il-6r expression is decreased in the colon during active uc. 22684895_1 microrna-590-5p regulates proliferation and invasion in human hepatocellular carcinoma cells by targeting tgf--beta rii. in addition, mir-590-5p downregulated the expression of tgf-beta rii by targeting the 3'utr of mrna. in conclusion, we determined that tgf-beta rii is a novel target of mirna-590-5p. 22684895_2 thus, the role of tgf-beta rii in regulating proliferation and invasion of human hccs is controlled by mir-590-5p. in other words, mir-590-5p promotes proliferation and invasion in human hccs by directly targeting tgf-beta rii. 22684895_3 these results indicate that tgf-beta rii was directly targeted by mir-590-5p in human hccs. 22684895_4 these results indicated that mirna-590-5p can directly downregulate the expression of tgf-beta rii to promote proliferation and invasion of malignant hepatocellular cancer. 22138289_2 in contrast, mir-221/222 had effects of anti-proliferation, anti-migration, and pro-apoptosis in ecs. the different expression profiles of their target genes, p27 , p57 , and c-kit between the two cell types might be related to the opposite effects 24130493_1 furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 reduced the ability of mir-155 to promote autophagy and mycobacterial elimination. 24130493_2 more importantly, our study demonstrated that mir-155 bound to the 3'-untranslated region of ras homologue enriched in brain , a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing rheb expression. 26633386_1 as expected, a negative control for the gga-mir-101-3p specific inhibitor did not inhibit ezh2 3'-utr luciferase activity , which demonstrated that gga-mir-101-3p negatively regulated expression of ezh2 by binding to the complementary sequence in the 3'-utr of ezh2 in a direct and sequence-specific manner. 25589783_1 our results identify fbxo11 as a novel mir-21 target gene,and demonstrate that the oncogenic mirna mir-21 decreases the expression offbxo11, which normally acts as a tumor suppressor, and thereby promotestumorigenesis. 26346167_1 furthermore, we identified and validated mapk1 as a direct target of mir-378. 26346167_2 we identified the downstream target gene of mir-378, mapk1, and confirmed that it regulated pca cells proliferation, cell cycle, wound healing potential, and invasion metastasis by targeting mapk1. 26346167_3 these findings indicate that mir-378 negatively regulates mapk1 expression by directly binding to its 3'-utr 22219180_1 using northern blot analysis, we found that, in particular, mir-26b is higher is all the adult vs. neonatal organs, in contrast to its predicted targets, gata4 and plc-beta1 proteins, which are generally higher in the neonatal tissue vs. the adult tissues . 22219180_3 the results suggested that mir-26b might target and depress gata4 expression. 22219180_4 figure 3 gata4 expression is directly suppressed by mir-26b. 22219180_5 these results confirmed that mir-26b is a negative regulator of gata4 expression in neonatal cardiac myocytes via directly targeting a predicted target site within the 3'-utr. 22219180_6 the data suggest that plc-beta1 is also a direct target of mir-26b. 22219180_7 figure 4 plc-beta1 is a negative regulator, and a target, of mir-26b. 23726841_1 mir-211 directly targets tgf-betarii with the mir-211-tgf-betarii-c-myc axis promoting hnscc progression. 23726841_2 taken together, mir-211 directly regulates tgf-betarii expression. 23726841_3 tgf-betarii was confirmed to be a direct target of mir-211 by experiments using mutant reporter constructs and expression analysis. 21731608_1 overexpression of mir-206 in normoxic conditions significantly reduced timp-3 mrna and protein levels . 21731608_2 thus, the seed sequence 1683/89 represents the specific target of mir-206 and is responsible for mir-206-mediated timp-3 down-regulation. 26449464_1 bioinformatics coupled with luciferase and western blot assays also revealed that mir-139-5p suppresses glioma cell proliferation by targeting eltd1 and regulating cell cycle. 26449464_2 collectively, our results demostrate that eltd1 is a bona fide target of mir-139-5p and mir-139-5p regulate the expression of eltd1 by directly targeting the 3 ' utr of eltd1. 26449464_3 our data shows that mir-139-5p interacts with eltd1 by directly binding eltd1 3 ' utr. 21278922_1 these data suggest that mir-137 down-regulates ctbp1, probably through specific interaction with the putative site at ctbp1's 3'utr, and ctbp1 is a direct targetfor mir-137. 21278922_2 as shown in fig.2c, over-expression of mir-137 led to a significant decrease in ctbp1 protein compared with the control. 21278922_3 therefore, we conclude mir-137 plays a critical role in ctbp1 expression. 21278922_4 this data suggests the function of mir-137 in melanoma is, at least in part, through its regulation of ctbp1. 22227196_1 these results strongly suggested an inverse correlation between the expression of snail1 and mir-30 during the tgf--beta1-induced emt in hepatocyte. 22227196_2 our results demonstrated that the mimics of mir-30a, -30b, -30c, -30d and -30e could significantly inhibit the luciferase activity of the wild-type snail1 3'-utr reporter but not that of the mutant reporter with mutated mir-30-binding site . 22227196_3 these results indicate that mir-30 can negatively regulate the expression of snail1 by direct targeting the 3'-utr of its mrna. 23825654_1 egfp fluorescence reporter vector analysis showed that mir-141 targets the 3'-untranslated region of the pten mrna. 23825654_2 this study demonstrated that mmu-mir-141 might influence cell proliferation and apoptosis in the endometrium by negatively regulating pten expression, and could also influence the number of embryo implantation sites. 23825654_3 this result confirms that mir-141 targets the 3'-utr of the pten mrna in stromal cells. 23825654_4 all these results suggested that mmu-mir-141 regulates protein expression of pten in stromal cells and that pten is a target gene of mmu-mir-141. 26334104_1 mir-133a regulates transcriptional activity of dapk2 by targeting the 3'-utr of dapk2. 26334104_2 targetscan algorithms showed that the 3使-utr segment of dapk2 gene contains mir-133a-binding site. 26334104_3 dapk2 expression decreased significantly in the mir-133a group compared with the sham group , whereas no significant difference was found between sham group and nc group . 20602797_1 mir-183 inhibits tgf-beta1-induced apoptosis by downregulation of pdcd4 expression in human hepatocellular carcinoma cells. 22469786_1 collectively, our findings suggest that mir-495 and mir-551a both act as tumor suppressors by targeting the prl-3 oncogene and inhibiting gastric cancer cell migration and invasion. 22469786_2 mir-495 and mir-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with prl-3. 22469786_3 qrt-pcr also showed that prl-3 mrna levels were similarly affected at 24 h post-transfection , suggesting that both mir-495 and mir-551a suppress prl-3 gene expression through binding 3'utr by inhibiting translation or causing mrna instability . 21364282_1 these data, together with previous observations that hfe and hjv mrna expression increased in the livers of mir-122-depleted mice , led us to hypothesized that mir-122 could be involved in maintaining iron homeostasis. 21364282_3 taken together, these data show that the 3'-utrs of hfe and hjv are direct targets of mir-122. 22490414_1 microrna-181a expression significantly down-regulated in cells transfected with microrna-181a inhibitor, compared with that in untransfectd cells . 22490414_2 cell apoptosis induced by ddp significantly decreased in cells transfected with microrna-181a inhibitor. 22490414_3 compared with ddp treated cells alone, bcl-2 expression strikingly was up-regulated and bax expression was down-regulated in cells transfected with microrna-181a inhibitor. 20131257_1 in silico analysis identified a sequence in the 3'-untranslated region of mmp-13 mrna complementary to the seed sequence of microrna-27b . 20131257_2 a strong correlation between the level of mir-27b expression and mmp-13 protein secretion was observed at later time points . 20131257_3 these results demonstrated that mir-27b bindhe seed sequence present in the 3'-utr of human mmp-13 mrna. 19409607_1 taken together, these results show that mir-145 directly target oct4, sox2, and klf4 3- utrs. 19409607_2 we conclude that the endogenous mir-145 in hescs is sufficient to repress oct4, sox2, and klf4 3- utr reporters directly. 19409607_3 these results indicate that the endogenous mir-145 exerts more repression on oct4 and klf4 than on sox2 during hesc differentiation. 19409607_4 the reduction of the oct4, klf4 protein, and sox2 mrna levels indicates that these endogenous reprogramming factors are posttranscriptionally controlled by mir-145 in hescs. 20826802_1 we next confirmed that mir-223 target the fbxw7 3'-untranslated region. 20826802_3 despite repressing the activity of the fbxw7 3'-utr reporter and mrna levels, mir-25 did not significantly reduce fbw7 protein abundance . 20826802_4 these data are consistent with the hypothesis that endogenous mir-223 modulates fbw7 expression. 20826802_5 together, data from these experiments support the concept that endogenous mir-223 can regulate fbw7 expression sufficiently to potentiate cyclin e activity in primary fibroblasts. 20826802_6 thus, we propose that mir-223 is part of a feedback loop connecting cyclin e activity to the regulation of fbw7 expression . 25406066_1 mutations of the two nucleotides within the predicted target site for mir-142-3p in the 3- utr of the apc mrna significantly weakened the ability of mir-142 to suppress the luciferase activity , suggesting that mir-142 specifically targets the predicted seed sequence in the 3- utr of the apcmrna to suppress the translation of the apc mrna. 25406066_2 these results suggest that mir-142 effectively targets the apc mrna and reduces the protein level of apc in the cells including the human breast cancer cells. 25406066_3 these results suggest that the activation of canonical wnt signaling pathway by mir-142 is mostly mediated by the ability of mir-142 to reduce the protein level of apc. 18841558_1 mir-21 may function as an antiapoptotic mirna in u87 cells. 18841558_2 inhibiting mir-21 expression could induce u87 cell apoptosis via caspase-9 and 3 activation, but not pten activation. 16940181_1 mir-17-5p represses estrogen/er-independent breast cancer cell proliferation by targeting aib1. 16940181_2 the inhibitory effects of mir-17-5p on estrogen independent breast cancer cell growth appears to be due to translational regulation of two important players in this pathway: aib1 and e2f1. 16940181_3 a recent report suggests that e2f1 is a target of mir-17-5p at the translational level . 16940181_4 by careful examination of e2f1 coding and noncoding 3'-utr, we found only one mir-17-5p recognition site. 16940181_6 therefore, there is a possibility that mir-17-5p may not directly regulate the expression of e2f1 but rather have an indirect effect on e2f1 activity. 16940181_7 this observation further established that mir-17-5p could directly inhibit the translation of e2f1, albeit less effectively than the reduction of aib1. 16940181_9 these results suggest that the negative influence of mir-17-5p on e2f1 was both directly and indirectly due to aib1 downregulation at least in breast cancer cells 26111641_1 adam17 was a direct target gene of mir-326. 26111641_2 this result indicated that mir-326 targeted adam17. 19223510_1 ubc9 is specifically suppressed by mir-30e and mir-30c. 19223510_2 western blot analysis revealed that both mir-30e and mir-30c suppressed ubc9 expression at the protein level . 19223510_3 to determine whether mir-30e and mir-30c affect the ubc9 mrna level, we carried out real-time rt-pcr analysis for the same cells transfected with mir-30e and mir-30c, and found that these two micrornas had no effect on the ubc9 mrna level , suggesting that they regulate ubc9 expression mainly through translation repression. 19223510_4 ubc9 is a direct target for mir-30e. 19223510_5 after transfection of 293t cells with this reporter construct along with mir-30e or mir-30c, we found that both mir-30e and mir-30c suppressed the luciferase activity by about 50% compared with the vector control , suggesting that ubc9 is a direct target for these two micrornas. 21186368_1 we found that both the alpha- and -beta-isoforms of the calcineurin catalytic subunit are direct targets of mir-499 and that mir-499 inhibits cardiomyocyte apoptosis through its suppression of calcineurin-mediated dephosphorylation of dynamin-related protein-1 , thereby decreasing drp1 accumulation in mitochondria and drp1-mediated activation of the mitochondrial fission program. 22248718_1 we discovered autophagy proteins atg4c and becn1 as cellular targets of mir-376b. 17906079_1 in this study, we showed that mir-24 could decrease human alk4 expression at the mrna and the protein levels through binding to the 3- -untranslated region of halk4 mrna, and interfere with activin signaling. 17906079_3 furthermore, the inhibitory effect of mir-24 on reporter expression was dose-dependent, but increasing concentrations of mir-205 had no effect on luciferase activity , indicating that mir-24 specifically target the halk4 3'-utr. 26259828_1 we then identified ptp1b, a ubiquitously expressed phosphatase, as the target of mir-744 that is responsible for enhancing type i ifn response. 26259828_2 finally, mir-744 expression was induced by type i ifn in rmcs. 26259828_4 therefore, we concluded that mir-744 positively regulates the type i ifn signaling pathway in human rmcs by targeting ptp1b. 26915294_1 specifically, we evaluated the expression of crucial prosurvival proteins bcl-2 and bcl-xl, as their 3'-utrs are wellcharacterized targets of the mir-15 and let-7 families, respectively .14,15 26915294_3 these data provide direct evidence that the decrease in bcl-2 or bcl-xl expression following hdaci is due to an upregulation of the mir-15 and let-7 families, respectively, that bind and promote their downregulation. 26915294_4 therefore, blocking the mir-15 and let-7 families from binding bcl-2 or bcl-xl in breast cancer cells prevented the downregulation of bcl-2 and bcl-xl and blunted the apoptotic response resulting from hdaci. 26915294_5 collectively, the data reveal a novel mir-15 and let-7 family-mediated mechanism of apoptosis that underlies hdaci-induced breast and lung carcinoma cell death. 26915294_6 figure 5 blocking mir-15 and let-7 families from binding bcl-2 and bcl-xl protects from hdaci-induced apoptosis 20332243_1 microrna145 target bnip3 and suppresses prostate cancer progression. 20332243_3 concomitant with the overexpression of mature mir145 by ad-mir145 infection , bnip3 protein level was significantly downregulated . 20332243_4 figure 4d schematically summarizes the data presented in the above sections showing bnip3 regulation by mir145, which may result from loss of tp53 function in prostate cancer cells. 23816136_1 mir-381 combined with 5-fu led to cd c2activation, mitotic catastrophe, and cell apoptosis through inhibitory wee1. 23816136_2 wee1 was also validated as the direct target of mir-381.mir-381, a novel intrinsic wee1 inhibitor, sensitizes renal cancer cells to 5-fu by upregulationof cdc2 activities in 786-o. 26629033_1 using the publicly available databases targetscan and miranda, we found two conserved mir-96 binding sites in the 3'-utrs of mtss1 gene . 26629033_2 these results indicated that the 3'-utr of mtss1 was a functional target of mir-96 in tca8113 cells. 26629033_3 together, our results suggest that mtss1 expression was partly regulated by mir-96, thereby inhibiting tscc progression. 22305007_1 we identify the jak/stat ligand, upd, as a target of mir-279 and show that knockdown of upd rescues the behavioral phenotypeof mir-279 mutants. 22305007_2 to determine whether mir-279 directly binds upd 3'-utr and inhibits its expression, we performed a luciferase reporter assay in drosophilas2 cells. 22305007_3 a chimeric mrna was made by fusing the firefly luciferase open reading frame to the full-length upd 3'-utr that contains all potential mir-279 binding sites . 22305007_4 as shown in figure 3d, upd mrna was up-regulated in adult brains of mir-279 null mutants. 22305007_5 on the other hand, mir-279 over-expression by a tim-gal4 driver reduced mrna levels of upd, with a higher dose of mir-279 producing a stronger effect . 22305007_6 we conclude that upd is a direct target of mir-279 in vitro and in vivo. 22305007_7 these data provide strong in vivo evidence that mir-279 regulates circadian rhythms by modulating levels of upd. 20227367_1 cab39 is a functionally relevant mir-451 target thus, mir-451 directly regulates cab39 expression by binding its predicted 3'utr targetsequence. 20227367_2 the effects of mir-451 on lkb1 activity are likely to be mediated directly by cab39. 20227367_3 this suggests that cab39 is a functionally relevant mir-451 targetin glioma cells. 20227367_4 taken together, these data show that mir-451 directly target and downregulates cab39, resulting in reduced lkb1-dependent phosphorylation of ampk and increased mtor activation. 25612549_1 bcl-2, bcl-xl and bcl2l11 which have an impact on the regulation of apoptosis were selected as potential hsa-mir-32-5p targets in caco-2 cells. 25612549_2 the observed coordinated regulation of hsa-mir-32-5p and bcl2l11 gene expression might be an indication that fatty acid-mediated downregulation of hsa-mir-32-5p in caco-2 cells could be accompanied by a downregulation of gene expression of apoptosis-inducing regulatory proteins whereas gene expression of apoptosis-inhibiting regulators such as bcl-2 and bcl-xl might be not directly affected by reduced hsa-mir-32-5p gene expression. 26816250_1 runt-related transcription factor 2 , a key transcription factor involved in oa, has been identified as a novel potential target of mir-105. in contrast, mir-105 inhibition promoted runx2 production in human chondrocytes . 26816250_2 taken together, these findings revealed that mir-105 inhibits the expression of runx2 through direct targeting of the 3'-utr. 22318941_1 the expression of microrna -23a, a candidate mir targeting pgc-1alpha and g6pc, was up-regulated in the mouseliver tumors as well as in primary human hcc. 22318941_2 we confirmed pgc-1alpha and g6pc as direct target of mir-23a and their expressions negatively correlated with mir-23a expression in human hccs. 22318941_3 the relative luciferase activity was reduced by 40% and 25% in pgc-1alpha and g6pc wildtype 3'-utr, respectively, but not in respective mutant 3'-utrs or psicheck2 vector alone , suggesting that mir-23a cognate sites are essential for negative regulation of luciferase expression driven by pgc-1alpha-3'-utr and g6pc-3'-utr. 22318941_4 these results indicate that mir-23a interferes with pgc-1alpha and g6pc expression at both the mrna and protein levels. 22318941_5 taken together, these data demonstrate that pgc-1alpha and g6pc are direct target of mir-23a. 21898400_1 mir-520c and mir-373 increased the expression of mmp9 by directly targeting the 3'utrs of mtor and sirt1 and suppressing their translation. 21898400_2 3'utrs of mrnas of mtor and sirt1 were the target of mir-520c and mir-373. 21898400_3 our data showed that the protein levels of both mtor and sirt1 were dramatically decreased by the transfected precursors of mir-520c and mir-373 ; whereas their mrna levels were not changed . 21898400_4 these results indicated that mir-520c and mir-373 decreased the protein level of mtor and activated the ras-raf-mek-erk pathway and nf-kappab factor via activating pi3k and ikk, and thus resulting in up-regulation of mmp9. 21898400_5 we hypothesized it was possible that up-regulation of mmp9 was via direct targeting of the 3'-utr of mrnas of mtor and sirt1 by mir-520c and mir-373, and blocking the translation of these two mrnas. 21898400_6 all of these mean that we have characterized a molecular mechanism of cooperative up-regulation of the expression of the mmp9 gene simultaneously by different signaling pathways via mir-520c and mir-373 targeting the 3'-utrs of mrnas of sirt1 and mtor . 26883272_1 ant2-specific shrna also inactivated the pi3k/akt signaling pathway in the h1975 and hcc827/gr cells, which was mediated by the suppression of mir-221/222 levels and by the subsequent restoration of pten. 26883272_2 an examination of the mirna profile after ant2 shrna transfection in a549 cells revealed that mir-221 and 222 were most markedly down-regulated , and a database search indicated that mir-221 and 222 were able to target pten. 22640741_1 to confirm mouse myostatin as a real mir-27a target, the entire wild-type 30'utr of mouse myostatin or the mutant 3'utr with a 7 bp mutation in the seed region was inserted downstream of the luciferase gene and assayed in hek 293t cells. 22640741_2 consistent with the data, no decrease in luciferase activity was observed when mir-27a mimics was transfected into hek 293t cells together with the mutant reporter , indicating that the predicted site is a direct target of mir-27a and it is solely responsible for mir-27a targeting of the mouse myostatin 3' utr. 21822301_1 mir-335 might suppress gastric cancer invasion and metastasis by targeting bcl-w and specificity protein 1 . 21822301_2 these results showed that sp1 and bcl-w are negatively regulated directly by mir-335 in gastric cancer cells. 21822301_3 these results demonstrated that mir-335 may targetsp1 and bcl-w in gastric cancer. 21822301_4 despite the effect of mir-335 on sp1 and bcl-w protein levels, no effect on sp1 and bcl-w mrna levels was detected . 21822301_5 although sp1 and bcl-w are negatively regulated directly by mir-335 in gastric cancer cells, mir-335 has no effect on the sp1 and bcl-w mrna levels detected by qrt-pcr. 21822301_6 these results highlight that mir-335 negatively regulates sp1 and bcl-w expression at the translational level in gastric cancer. 26622784_1 furthermore, luciferase reporter assay analysis identified zeb2 as a direct target of mir- 215. 26622784_2 these data indicate that zeb2 is a direct target of mir-215 in nsclc. in addition, zeb2 was identified as a direct target of mir- 215. 26057744_1 we confirm that the crot, hadhb and npc1 genes are the target genes of mir-33 in geese according to the dual luciferase reporter gene system. 25445282_1 as expected, we also found that linc-pou3f3 expression was negatively correlated with the mrna level of pou3f3 . 25445282_2 our results indicate that linc-pou3f3 might affect glioma development via altering expression level of pou3f3, and lead us to believe that linc-pou3f3 may also have a crucial regulatory role in glioma progression. 25531324_2 these results strongly suggest that mir-185 is one of the upstream molecules regulating stim1 expression in cancer. 25531324_3 stim1 is a direct functional target of mir-185 in crc metastasis. 25531324_4 taken together, these results suggest that stim1 is a potential functional target of mir-185. in summary, our results suggest that stim1 is a direct functional target of mir-185 and that this novel mir-185/stim1 axis has an important role in the regulation of crc metastasis. 25955794_1 eif4b is a direct target of mir- 216a. 25955794_2 mir- 216a inhibits the progression of oscc cells by targeting eif4b. 22227154_2 we found that qki mrna is down- or up-regulated by two-fold upon mir-214 overexpression or inhibition, respectively , demonstrating a regulation by mir-214 not only by translational repression, but also by affecting mrna stability. 22227154_3 more importantly, qki transcript levels were up-regulated in different tissues of antagomir-214-treated mice, indicating that qki is targeted by mir-214 in vivo as well . 22227154_5 here, we report a novel role for mir-214 in regulating angiogenesis and identify quaking as a direct target of mir-214. 21701675_1 as validated by qpcr and luciferase reporter assay, our results showed mir-145 suppressed integrin-beta8 expression in both human corneal epithelial cells and primary cepcs. 21701675_2 similar reduction of itgb8 expression was observed in primary human cepcs transfected with mir-145 . 21701675_3 sequences of two mir-145 binding sites located in human itgb8 3'-utr. 20571053_1 overexpression of mir-1, but not mir-126, dramatically decreased the activity of the luciferase reporter bearing the 3' utr of twf1. 20571053_2 by contrast, neither mir-1 nor mir-126 inhibited the activity of the luciferase reporter containing the twf2 3' utr . 20571053_3 collectively, our results indicate that twf1 is directly targeted by mir-1 and this inhibitory effect is mediated through its 3'-utr. 20571053_4 a mild change in the level of mir-1 did not affect the amount of twf1 mrna. 20571053_5 these results suggest that twf1 is de-repressed by mir-1 during the pathogenesis of cardiac hypertrophy. 23194063_1 curcumin and rl197 inhibited rko and sw480 colon cancer cell growth and induced apoptosis, the mechanism of curcumin-/rl197-induced repression of sp transcription factors was ros-dependent and due to induction of the sp repressors zbtb10 and zbtb4 and downregulation of micrornas -27a, mir-20a and mir-17-5p that regulate these repressors. 23143398_1 mir-133 directly targets and negatively regulates prdm16, and inhibition of mir-133 or mef2 promotes differentiation of precursors from bat and sat to mature brown adipocytes, thereby leading to increased mitochondrial activity. 23143398_2 this demonstrates that mir-133 directly interacts with the predicted target sites in the prdm16 transcript. 23143398_3 these results indicate that the effect of mir-133 on brown adipocyte differentiationis largely mediated by prdm16 as its direct target. 21799781_1 ckap5 was confirmed as a new target of mir-155. 21799781_2 for kif11 and ckap5, regulation was detected at the protein level by silac, as well as by western blot analysis, but only the 3'-utr region of ckap5 is targeted by mir-155 using luciferase sensor constructs . 21799781_4 ckap5 has been identified as a direct target of mir-155 and pcm1, kif11, rbm4 and tuba1c are putative direct target of mir-155, due to their detection by prediction algorithms or seed sequence matches. 26255201_1 mir-130a and mir-130b decreased ppar纬 expression by targeting the 3'-utr of ppargamma mrna in rat hsc-t6 cells. 26255201_2 transforming growth factor--beta1 may mediate mir-130a and mir-130b overexpression, ppargamma downregulation, and ecm genes overexpression in cell culture. 26255201_3 these findings suggest that mir-130a and mir-130b are involved in downregulation of ppar纬 in liver fibrosis. 26255201_4 fig. 2. mir-130a or mir-130b specifically inhibits pparg by targeting 30-utr of ppargamma. 26255201_5 these data strongly suggest that mir-130a and mir-130b negatively regulate ppargamma expression through direct targeting of the 3'-utr of ppargamma mrna in rat hscs. 23420759_1 his effect may be a consequence of a decrease in the level of hsa-mir-125a, which promotes erbb2 mrna decay and inhibits translation. 23420759_2 these findings suggest that the erbb2 mrna increase may be caused by diminished levels of inhibitory hsa-mir-125a. 23420759_3 this effect may be a consequence of a decrease in the level of hsa-mir-125a, which promotes erbb2 mrna decay and inhibits translation. 19844573_1 figure 8c shows that mir-378 significantly decreased luciferase activity in luc-gal-utr-transfected cells, but did not affect luciferase activity in the luc-gal-mut-transfected cells, indicating targeting of galnt7 3'utr by mir-378. 19844573_2 to confirm the down-regulation of galnt7 by mir-378, cell lysate was prepared from the cells transfected with mir-378 or gfp and analysed by western blot. 19844573_3 the experiments concluded that the presence of nephronectin 3'-utr arrested mir-378 and freed galnt7 mrna for galnt7 protein expression. 22792185_1 in conclusion, our luciferase expression data demonstrate that mir-138 and mir-709 can efficiently bind and regulate the expression of sox-2, c-jun and egr2 in the context of an in vitro experiment. 26202364_2 compared with the controls, mir-497 significantly decreased the vegfa mrna expression level . 26202364_3 and the vegfa protein level was also significantly decreased by transfection of mir-497 . 26202364_4 the results confirmed that vegfa is a direct target of mir-497. 22498974_1 mirna-34b and mirna-34c are up-regulated and directly targetnotch1 during bmp2-induced c2c12 osteoblast differentiation. 22498974_2 these data suggest that mir-34b and/or -34c directly bindto these two sites in the 3'-utr of notch1 and thereby regulate notch1. 22498974_3 next, to examine whether mir-34b and -34c directly regulate notch1 by binding to these two putative sites at the 3'-utr of notch1, the entire 3'-utr region was cloned into the luciferase reporter vector psicheck2 and co-transfected with the mir-34b, -34c or negative control mimic in hela cells. 26572100_1 developmentally regulated gtp-binding protein 2 and pre-b cell leukemia homeobox 2 were identified as downstream targets of mir- 1915- 3p, which was shown to bind directly to the 3'-untranslated region of drg2 and pbx2, subsequently lowering their mrna and protein expression levels. 26572100_2 mir- 1915- 3p prevented vp16-induced cell apoptosis, and further investigation revealed that developmentally regulated gtp-binding protein 2 and pre-b cell leukemia homeobox 2 were direct and functional targets of mir- 1915- 3p. 26572100_4 the experiments performed in the present study demonstrated that drg2 and pbx2 were targets of mir- 1915- 3p. 25799050_2 taken together, these findings revealed that mir-30c inhibited adam19 expression by directly targeting the adam19 3'-utr. 25799050_3 adam19 might be a functional target of mir-30c. 25092144_1 knockdown of mir-155 or overexpression of pu.1 blocks proliferation and induces apoptosis of flt3-itd-associated leukemic cells. 25092144_2 our data demonstrate a novel network in which flt3-itd signaling induces oncogenic mir-155 by p65 and stat5 in aml, thereby targeting transcription factor pu.1. 19710019_1 due to the tissue specific nature of mir-1/206 for skeletal muscles, we investigated the role of mir-1/206 in the development of rhabdomyosarcoma. 19710019_4 using bioinformatics, we identified two putative mir-1/206 binding sites within the 3-untranslated region of the human c-met mrna. 19710019_5 mir-1/206 was then shown to have activity on mrna expression by targeting the c-met 3-utr. 19710019_7 conversely, upregulation of c-met was confirmed in tissue samples of human rhabdomyosarcoma, with its level inversely correlated with mir-1/206 expression. in vivo, mir-1/206 expressing tumor cells showed growth delay in comparison to negative control. 19710019_8 our results demonstrated that mir-1/206 suppressed c-met expression in rhabdomyosarcoma and could function as a potent tumor suppressor in c-met overexpressing tumors. 23807228_2 we also demonstrated that mir-185 negatively regulates atr expression at post-transcriptional level. 19654003_2 these findings may suggest that impact of mir-133b on cell survival is likely mediated by target beyond mcl-1 and bcl2l2. 19654003_3 however, screening of seven nsclc cell lines did demonstrate that cell lines highly expressing mir-133b had lower levels of both mcl-1 and bcl2l2 protein .however, 21847633_1 mir-199a directly recognize the 3'utr of hif-1alpha transcripts. 21847633_3 taken together, our results demonstrate that mir-199a directly recognize the 3'-utr of hif-1a transcripts . 21687694_1 hsa-mir-99a regulates the expression of igf-1r through interaction with its 3'utr. 21687694_2 this reciprocal expression pattern suggests a possible relationship between hsa-mir-99a and igf-1r. 21687694_3 in contrast, the level of igf-1r protein was dramatically reduced in pre-mir-99a expressing cells, as determined by western blot analysis . 21687694_5 collectively, these results support our hypothesis that igf-1r is a direct target of hsa-mir-99a. 21687694_6 collectively, our results suggest that mir-99a and igf-1r are co-regulated, functioning together to maintain the balance between keratinocyte proliferation and differentiation. 22099878_1 after targetprediction software programs indicated a role for mir-21 in ccl20 regulation, we applied the luciferase reporter assay system to demonstrate that mir-21 functionally interacts with the 3'utr of ccl20 mrna and down-regulates ccl20 in mir-21 mimic transfected crc cell lines . 22099878_3 as mir-21 regulates the expression of a luciferase construct which contains the 3' utr of ccl20 mrna, we suggest that mir-21 regulates ccl20 gene expression by a regulatory element present in the 3' utr of ccl20 mrna. 25562167_2 runx1 was identified as a direct target of mir-302b, and knockdown of runx1 inhibited cell growth in a manner similar to mir-302b overexpression, whereas introduction of a 3'utr mutant of runx1 reversed the suppressive effect of mir-302b. 26721185_1 the ppar纬-mediated inhibition of hmgb1 is associated with the upregulation of mir-142-3p, which can target the 3'-utr of hmgb1, by directly binding to the ppre in the mir-142-3p promoter region. 26721185_3 these results suggest that ppar纬-mediated upregulation of mir-142-3p inhibits the hmgb1 expression, which, in turn, is a novel anti-inflammatory mechanism of ppar纬 and has an important role in the treatment of inflammatory diseases. 19823043_1 mutations of the predicted mir-195 targetsites in the e. although the wee1 3'utr also has a predicted site for mir-372, overexpression of mir-372 did not repress wee1 3'utr in the luciferase assay . 19823043_2 to test whether mir-195 can regulate wee1 directly by targeting its 3'utr, we used a luciferase assay in a hct116 dicer hypomorph line. 19823043_3 therefore these data show that mir-195 is sufficient to directly regulate the wee1 3'utr. in summary, these data are consistent with the model that mir-195 represses wee1 and therefore affects hesc cell cycle . 22595676_1 target protection analyses in vivo identify the progenitor-promoting genes her6 and zic5 and the cell-cycle exit-promoting gene elavl3/huc as sequential targets of mir-9 as neurogenesis proceeds. 22595676_2 together, these results validate elavl3 as a direct mir-9 target in a later step of neurogenesis progression, and demonstrate that a major function of mir-9 is to delay the onset of effective neuronal differentiation. 22595676_4 we demonstrate that mir-9 initially drives progenitor commitment through its direct inhibition of her6 and zic5, but concomitantly exerts an opposite effect on neurogenesis progression, via its direct inhibition of elavl3. 23072816_1 mir-10a* and mir-21 regulate epc senescence via suppressing hmga2 expression and modulation of micrornas may represent a potential therapeutic intervention in improving epc-mediated angiogenesis and vascular repair. 23072816_2 these data indicate that mir-10a* and mir-21 directly interact with hmga2 3'-utr, repressing hmga2 expression. 20679397_1 the mir-451 target sequence in ywhaz 3- utrs is conserved across species . 20679397_2 to directly test for possible regulation of ywhaz by mir-451, ter119+-enriched 14.5 dpc fetal liver cells were harvested from mir-451-/- and mir-451+/+ animals, and quantitative real-time rt-pcr for six transcripts encoding 14-3-3 isoforms was performed. of these transcripts, only ywhaz was up-regulated in mir-4511-/- cells compared with mir-451+/+ cells . 20679397_3 immunoblot analysis revealed - 1.5-fold up-regulation of 14-3-3ζ protein levels in mir-451+/- cells and twofold up-regulation in mir-4511-/- cells . 20679397_4 a luciferase reporter fused to the ywhaz 3- utr was repressed by mir-451 in cos-1 cells, and mutation of the mir-451-binding site within this utr abolished repression by mir-451 . 20679397_5 these data demonstrate that repression of 14-3-3ζ enhances erythroid differentiation in the absence of mir-451, and strongly supports the conclusion that mir-451 repression of 14-3-3ζ enhances erythroid differentiation. 23087084_1 moreover, we demonstrated that mir-106b downregulates apc expression by directly targeting the 3'-untranslated region of apc messenger rna. 23087084_3 collectively, these results demonstrate that apc is a bona fide target of mir-106b. 23087084_4 mir-106b suppresses apc expression by directly targeting the apc 3'-utr. 22510281_2 investigate the potential interaction between mir-153 and app/aplp2, human app and aplp2-3'utr were subcloned downstream of the renilla luciferase coding sequence and cotransfected into 293 t cells with mir-153 expressing vector or negative control plasmid. 22510281_3 the results of relative luciferase assay showed that transfection of mir-153 produced a moderate but significant decrease in luciferase expression of app and aplp2 by 15% and 27%, respectively , when compared with that in the controls. 22510281_4 however, when the core binding regions of mir-153 within app and aplp2 were inactivated by site-directed mutagenesis, the reduction induced by transfection of mir-153 was abolished. 26823765_1 creb, target gene of mir-134, also an important anti-apoptotic gene in many processes, was decreased response to the increase of mir-134 . 26823765_2 therefore, c/ebpalpha inhibited cell proliferation via regulating mir-134/creb. 26398017_1 mir- 1297 targets the 3'utr of hmga2. 26398017_2 these results indicate that hmga2 is a direct target of mir- 1297. 22473996_1 genetic and signaling perturbations presented the evidence that mir-155 regulates pka signaling by directly targeting a negative regulator of pka, protein kinase inhibitor alpha . 22473996_3 our data support the evidence that mir-155 modulates pka signaling, as pki-alpha, a negative regulator of pka signaling, is a direct target of posttranscriptional repression by mir-155. 26883054_1 by using computational analysis, we identified that kras is a virtual target of mir-126, and such association was verified by using luciferase assay. in addition, we validated kras as a target of mir-126, and verified the regulatory association between mir-126 and kras and their roles in the development of tscc. the results further confirmed the regulatory relationship between the mir-126 and kras in the stcc cells. 26883054_2 these findings further demonstrated that kras is a direct target of mir- 126 in tscc cell lines. 26883054_3 in this study, we identified that kras is a virtual target of mir-126 with multiple hits in the 3'-utr of the gene by searching the online mirna database and using computational analysis, which was further confirmed by luciferase reporter system, showing that the luciferase activity of the cells cotransfected with kras 3'-utr and mir-126 mimics were significantly lower than that of the cells transfected with kras 3'-utr and scramble controls, while the luciferase activity of the cells transfected with kras 3'-utr and mir-126 inhibitors were substantially higher than that of the cells transfected with scramble controls and kras 3'-utr. 26064312_2 down-regulating mir-26b under the condition of hypoxia subsequently up-regulated pten in neonatal cardiomyocytes. 26064312_3 second, as pten was the direct target of mir-26b during the regulation of i/r injury. 20388800_1 the oncogenic mechanism of mir-483-3p was at least partially clarified by the finding that it could modulate the proapoptotic protein bbc3/puma and mir-483-3p enforced expression could protect cells from apoptosis. 20388800_2 to test the direct interaction of mir-483-3p with 3'-utrs, the predicted wild-type and mutant mir-483-3p targetsites of puma mrna gene were cloned downstream of the luciferase reporter gene of pgl3-control vector. 25518924_2 blot analysis showed that the expression of programmed cell death 4 , which was predicted as the target gene of mir-183 by microarray profiling and bioinformatics predictions, decreased when mir-183 was over-expressed. 26617801_1 these results indicated that creb1 is a potential target of mir-506, and that mir-506 negatively regulated creb1 gene expression in escc. 20696910_1 second, ryhb directly represses the translation of cyse, which encodes a serine acetyltransferase that uses serine as a substrate for cysteine biosynthesis. 26771762_1 to validate whether the mir-103 regulates pdcd10 30utr directly through binding sites, wildtype and mutant pdcd10 were constructed and cloned downstream of a luciferase reporter gene. 26771762_2 the over-expression of mir-103 in pc-3 cellsdecreased the level of pdcd10 mrna. 18823650_1 we tested the hypothesis that m-csf could be a direct target of mir-130a by cloning the full length 3'-utr of the human m-csf mrna downstream of the luciferase gene in the pgl3 plasmid for a luciferase targeting assay. 18823650_4 we can conclude that the m-csf is a bona fide target of mir-130a. 21293058_1 the mir-193a-5p demonstrated the strongest regulation of the p73 3- utr, and we next studied its physiological regulation in more detail. 21293058_2 given that p73 activation following cisplatin treatment is thought to rely on both p63 degradation and p73 posttranslational modification , these findings support a p63/p73-dependent mechanism for mir-193a induction following cisplatin treatment in scc. 21293058_3 these findings led us to hypothesize that mir-193a induction by chemotherapy may function to induce chemoresistance through feedback inhibition of p73. as predicted by this model, transfection of a mir-193a mimic suppressed endogenous p73 mrna levels ,4a, while expression of a specific antagomir caused an increase in endogenous p73 mrna in both human and murine cells . 21293058_4 most notably, the antagomir experiments demonstrate that mir-193a is a constitutive inhibitor of p73 in scc cells. 19574461_4 here, we report that mir-23a is a pro-hypertrophic mirna, and its expression is regulated by the transcription factor, nuclear factor of activated t cells . 19574461_6 knockdown of mir-23a could attenuate hypertrophy, suggesting that mir-23a is able to convey the hypertrophic signal. 19574461_7 in exploring the molecular mechanism by which mir-23a is up-regulated, we identified that nfatc3 could directly activate mir-23a expression through the transcriptional machinery. 19703567_1 using lentiviral-mediated mirna expression, we show a significant downregulation of bdnf and d3r both at mrna and protein levels by mir-124 and let-7d, respectively. 19703567_2 lv-mir-124 overexpression in ng108-15 cells resulted in significant, concentration-dependent down-regulation of bdnf , in perfect correlation with the targetprediction data. 19703567_4 a significant reduction by lv-mir-124 of bdnf mrna levels of 22, 47, and 49% was found by qrt-pcr =265.95, 19703567_6 at the protein level, significant downregulation by lv-mir-124 of bdnf was also observed = 23.80, 22634176_1 these data indicated that mir-155 functions by directly targeting socs1 expression. 22634176_2 these data suggested that mir-155 enhances tnf-alpha-induced jnk activation by targeting socs1 in mc3t3-e1 cells. 25840419_2 mir-195 expression and effects on chek1 as a target of mir-195. 22815348_1 luciferase reporter assays revealed that tab2 was a target gene of mir-155, which was confirmed by western blotting. 22815348_4 the results showed that mir-155 suppressed the expression of tab2 at the protein level . in view of the decreased expression of mir-155 in active bd patients compared with the healthy controls and the direct inhibitory effect of mir-155 on target tab2, we further investigated the tab2 protein expression in dcs from bd patients with active uveitis. 26910912_1 these findings further confirmed that mir-410 could inhibit slc34a2 expression transcriptionally and post-transcriptionally 19391107_1 microrna 145 has been proposed as a tumor suppressor. it was previously shown that mir145 targets the 3' utr of the insulin receptor substrate-1 and dramatically inhibits the growth of colon cancer cells. 19391107_3 we show here that an irs-1 lacking its 3' utr is no longer down-regulated by mir145 and rescues colon cancer cells from mir145-induced inhibition of growth. 19391107_4 an igf-ir resistant to mir145 is not down-regulated by mir145 but fails to rescue colon cancer cells from growth inhibition. 19391107_5 these and other results, taken together, indicate that down-regulation of irs-1 plays a significant role in the tumor suppressor activity of mir145. 24457952_1 long non-coding rna uca1 promotes breast tumor growth by suppression of p27 20023698_2 these results suggest that mir-181b interferes with timp3 expression at mrna and/or protein levels. 20023698_3 the normalized luciferase activity increased by 60% in pis0-timp3-3'utr transfected cells but not in pis0-timp3-3'utrdelta expressing cells , indicating that mir-181b negatively regulates timp3 expression by interacting with its 3'-utr. 20023698_4 taken together, these data suggest that timp3 is a functional target of mir-181b in hcc cells. 24944883_1 in response to mir-34a overexpression in both hngc-2 and nsg-k16 cells, there was a significant down-regulation of rictor at protein level indicating it to be a functional target of mir-34a . 24944883_2 next, by luciferase reporter assay we confirmed that rictor was a direct target of mir-34a in glioma cells. 24944883_5 our data indicated that mir-34a directly bound to 3'utr of rictor and suppressed the luciferase activity in hngc-2 and nsg-k16 cells . 24944883_6 this data indicated that mir-34a directly targets rictor in glioma stem cells. 24944883_7 these experiments confirmed that rictor was a functional target of mir-34a in glioma stem cells. 26819680_1 the expression of e-cadherin was significantly upregulated, whereas vimentin and snai2 were significantly downregulated in both mir-203-expressing skov3 and ovcar3 cells when compared to control cells. 26697292_2 overexpression of mir-431 significantly reduced the expression of zeb1 protein and resulted in increase of e-cadherin level and decrease of vimentin level in hcclm3 cells . in contrast, knockdown of mir-431 increased the level of zeb1 protein and led to decrease of e-cadherin expression and increase of vimentin expression . 26697292_3 a dual-luciferase reporter assay was performed to disclose whether mir-431 directly binds to the 3'-utr of zeb1 mrna. 26697292_4 as expected, mir-431 obviously reduced the luciferase activity of zeb1 containing a wt 3'-utr. 26697292_5 our results indicate that zeb1 is a functional target of mir-431 in hcc. 20300657_1 mir-218 inhibits invasion and metastasis of gastric cancer by targeting the robo1 receptor. 20300657_2 decreased mir-218 levels eliminate robo1 repression, which activates the slit-robo1 pathway through the interaction between robo1 and slit2, thus triggering tumor metastasis. 20300657_3 robo1 was a direct functional target of mir-218 in gc metastasis. 20300657_4 the results showed a negative correlation between the levels of mir-218 and robo1 mrna in these cells . 20300657_5 furthermore, we observed that robo1 mrna and protein levels were decreased when mir-218 was expressed by pgenesil-1-mir-218 in mkn28-m cells . 20300657_6 therefore, we concluded that the inserted fragment of robo1 was the target of mir-218. 21893058_1 mir-483-5p has been shown to function by directly binding to the 3'utr of its targetgene srf mrna. 21893058_2 mir-483-5p suppressed the expression of srf by binding to its 3'-utr. 21893058_4 the results showed that the mrna level of srf was trivially suppressed , and the protein level of srf was obviously suppressed in huvecs transfected with the mir-483-5p mimic. 21893058_5 we used a luciferase experiment to identify that mir-483-5p suppressed the expression of srf by binding to its 3'-utr. 18838543_1 apoptosis can be triggered by depleting mir-bart5 or inducing the expression of puma. 22426479_1 mir-542-5p directly target egfr in lung cancer cell lines. 22426479_2 to identify mirnas that targetegfr, we performed a bioinformatics analysis and found that mir-542-5p down-regulates egfr mrna and protein expression in human lung cancer cells . in contrast, mirna-542-5p inhibits egfr by a different mechanism-down-regulating its levels by binding to the 5'-utr of the egfr mrna. 22426479_3 therefore, the suppression of egfr by mirna-542-5p should not be affected by mutations in the coding sequence. 22426479_4 agents such as mir-542-5p that down-regulate expression of egfr as well as some of its signaling effectors may have significant therapeutic potential in a range of human cancer types. 22869051_1 we also identified a novel target of mir-145, nedd9 and found that its regulation modulates the invasion potential of gliomas. 22869051_2 the overexpression of mir-145 affects the aggressive and invasive features of gb-ns, as confirmed by a greater differentiation of the tumor phenotype and a highly significant decrease in nedd9, supporting the concept that mir-145 plays an important role in glioblastoma invasiveness by regulating nedd9. 22869051_3 together, these results suggest that mir-145 down-regulates nedd9, and nedd9 down-regulates mir-145, forming a double-negative feedback loop in gb-ns. 22929890_1 altogether, these results show that downregulation of mirna-214 leads to upregulation of pten, which subsequently reduces akt phosphorylation. 26396139_1 measuring genes predicted to regulate apoptosis and autophagy, mirna-221 mimic decreased ddit4, tp53inp1, and p27 at both messenger rna and protein levels, and reduced mrna of bak1 and puma and proteins of bim and bmf. 23142283_2 furthermore, we detected mir-29c repressed expression of anti-apoptotic factors, mcl-1 and bcl-2 in npc tissues and cell lines. 21248297_2 western blotting showed that knockdown of mir-200c expression was associated with increased expression of ppp2r1b, a subunit of protein phosphatase 2a, which resulted in reduced expression of phospho-akt. 11805044_2 tlc1 impact on dsb repair pathways. 26437223_1 the comparison in gscs between the expression of mir-135b and the protein level of the three targets showed an inverse correlation , thus supporting the hypothesis that adam12, smad5 and gsk3 -beta are indeed mir-135b targets in gscs. 26437223_2 these results strongly support a direct targeting of adam12 by mir-135b as previously demonstrated for the other two targets smad5 and gsk3-beta . 21769867_1 mir-133a suppressed the activity of luciferase when thereporter gene was linked to a 3'-utr segment of col1a1 . 21769867_2 mir-133a and mir-29b targetcol1a1 mrna. 21769867_3 our data strongly suggest that myocardial fibrosis could be modulated not only by mir-29b, which is expressed in the fibroblasts, but also by mir-133a, muscle specific, through a synergic action on col1a1 mrna expression. 21769867_5 in vivo, myocardial down-regulation of mir-133a and mir-29b could represent a regulatory mechanism that contribute to heart injury leading to myocardial fibrosis through an increase in col1a1 expression. 20799856_2 consistently, mir-1 mimic reduced klf4 3'utr luciferase activity, which can berescued by mutating the mir-1 binding site on the klf4 3'utr in the reporterconstruct. 20799856_3 further, klf4 expression was restored by mir-1 inhibitor , consistent with the functional prediction that mir-1 binding to the klf4 3'-utr would lead to klf4 translational repression. 20799856_4 taken together, these results strongly support that mir-1 regulates expression of klf4 at the post-transcriptional level during mouseesc/smc differentiation 22166214_1 it was shown that mir-22 may function as either oncogene or tumor-suppressor through downregulating various gene targets, such as pten, cdk6, sirt1, sp1, and evi-1 , depending on the context of malignancies examined. 22166214_2 in our effort to determine the potential target genes of uv-induced mir-22, we found that increased mir-22 correlated with reduced expression of pten , whose inhibition has been linked to carcinogenesis of skin cancer upon uv radiation . 22166214_3 furthermore, the decrease of pten expression in response to uv radiation was rescued by expressing a mir-22 sponge inhibitor in hek293t cells , suggesting that mir-22 played a critical role in pten repression in cells upon uv treatment. 25511701_2 these results strongly suggest that mir-218 plays a tumor suppressor role in pc cells. in addition, our data firstly demonstrated that mir-218 directly regulates oncogenic tpd52 in pc3 cells and the mir-218-tpd52 axis can regulate growth of this prostate cancer cell line. 23812098_1 the rora 3- utr contains two clusters of predicted mirna binding sites, each including four conserved mir-17~92 binding sites . 23812098_2 rora is a functionally relevant mir-17~92 target. 23812098_3 we conclude that all 4 mirna families represented in the mir-17~92 cluster contribute to a robust inhibition of rora expression. 26055960_1 we showed, after 96 h from virus infection, a down-regulation of mir-155 and an increase of mrna level of its gene target spi1 and cebpb . 26055960_2 we found, in flt3-mutated aml, a significant down-regulation of mir-155 target genes cebpb and spi1 and up-regulation of mir-155 regulator genes jun and runx1. 26055960_3 we also showed that pkc412-related flt3 inhibition, in mv4-11 cell line, causes down-regulation of mir-155 and increased level of mrna and protein of mir-155 target spi1. 26055960_4 we showed in experiments of mir-155 mimic in k562 cell line, a high increase of mir-155 and an inverse correlation with the mrna levels of its targets spi1 and cebpb. 25686745_1 upregulation of mir-370 obviously attenuated the ccl 4 -induced liver fibrosis in rats. 25686745_2 mir-370 was directly bound to the 3 ' utr of smoothened and suppressed the expression of smo in hscs and fibrotic livers. 25686745_3 we also illustrated that smoothened , one positive regulator of the hh pathway, is a direct target of mir-370 in activated hscs during liver fibrosis. 25686745_4 these data indicated that smo is a direct downstream target of mir-370. 25686745_5 taken together, these data further confirmed that mir-370 targets to smo and decreases the activation of hh pathway in vivo. 26400984_1 taken together, our present results suggest that mir-203 is a negative regulator of c-abl expression in smooth muscle cells. 26400984_2 the results suggest that mir-203 is able to degrade c-abl mrna and protein. 20931396_1 we have shown that mirna-7 and mirna-331-3p directly regulate expression of egfr and her2, respectively, in glioblastoma and prostate cancer cell lines. 20931396_2 using quantitative rt-pcr, we have shown that mir-7 and mir-331-3p regulate degradation of egfr and her2 mrna, respectively . 20931396_3 mir-7 and mir-331-3p directly targetthe egfr and her2 mrna 3'-utrs, blocking expression of these targetmolecules and reducing activity of the akt signaling pathway in glioblastoma and prostate cancer cells . 23828572_1 when suppressed by mir-874, caspase-8 lost the ability to repress necrotic program. in exploring the molecular mechanism by which mir-874 expression is regulated, we identified that foxo3a could transcriptionally repress mir-874 expression. 19273599_1 based on these data, we hypothesized that increased translation of p27 during hl60 cell differentiation is accompanied by reduced expression of mir-181a. 19273599_2 we conclude that mir-181a inhibits cap-dependent translation of p27 mrna. 19273599_3 these results support the conclusion that mir-181a regulates the translation of p27 mrna in myeloid cells. 25385479_1 further investigation demonstrated the regulation of mir-410 in os cells via vegf. in vitro mtt assay, transwell, and flow cytometry showed that transfection of the mir-410 expression plasmid inhibited cell proliferation and contributed to apoptosis in os cells. 25385479_2 moreover, restoration of vegf reversed the effect of mir-410 on os cells, and upregulated the expression of phosphorylated akt. 20466885_1 we identified putative binding sites for mouse mir-33 in the 3'-utr of several genes involved in cellular cholesterol mobilization, including abca1 and abcg1 and the endolysosomal transport protein npc1 , suggesting that mir-33 coordinates cholesterol homeostasis through these pathways . 20466885_2 fig. 2 posttranscriptional regulation of abca1, abcg1, and npc1 by mir-33. 20466885_3 although we found that mir-33 comparably repressed abca1 in cells of mouse and human origin, this was not the case for npc1 and abcg1. 20466885_4 mir-33 strongly suppressed npc1 protein in cells of human origin , whereas in mouse cells, mir-33 suppressed npc1 protein levels only modestly and had no effect on npc1 mrna levels . 20466885_5 furthermore, transfection of human macrophage, hepatic, and endothelial cells with mir-33 had no detectable effect on abcg1 protein . 20466885_6 conservation map analysis revealed that although the predicted mir-33 target sites in the 3'-utr of mouse abca1 and npc1 are highly conserved , the putative sites for mir-33 in the 3'-utr of abcg1 are present only in mouse and rat. 20466885_7 moreover, a second mir-33 binding site was identified in human npc1 , highlighting the species-specific regulation of cholesterol metabolism genes by mir-33. 20466885_8 together, these experiments identify abca1 and npc1 as conserved targets of mir-33, whereas abcg1 is a target only in the mouse. 20466885_9 fig. 3 mir-33 specifically targets the 3'-utr of abca1, npc1, and mouse, but not human, abcg1. 26191221_1 taken together, these data strongly suggested that timp2 is a direct target of mir-221 in ccrcc. 26191221_2 collectively, these results demonstrated that mir-221 could promote the proliferation, migration and invasion of renal cancer cells via directly down-regulating timp2 expression. 25360821_1 our data suggest a critical role of mir-30a-3p in the regulation of baff expression, which could have a major impact in the regulation of the autoimmune responses occurring in ra and ssc. 25360821_2 mir-30a-3p modulates baff expression in rafls and sschdf. 25360821_3 these data demonstrate that mir-30a-3p is implicated in the negative regulation of baff synthesis in poly - and ifn-gamma-activated fls and hdf. 25360821_4 altogether, these data suggest that baff transcripts can be directly targeted by mir-30a-3p for post-transcriptional regulation. 20574517_1 we demonstrate that mir-128a has growth suppressive activity in medulloblastoma and that this activity is partially mediated by targeting bmi-1. 20574517_2 co-transfection with mir-128a significantly decreased renilla luciferase activity in the bmi-1 target site vectors but not in the mutated site vectors . 20574517_3 this data suggests that bmi-1 is a target of mir-128a. 20574517_4 mir-128a decreased bmi-1 protein levels in daoy cells consistent with the luciferase data. . 20574517_5 this is consistent with our findings that mir-128a decreases bmi-1 and increases p16. 20574517_6 rescue experiments with bmi-1 lacking its 3'-utr also revealed that mir-128a target bmi-1 and thus leads to increase in ros level in cells . 18663744_5 furthermore, this mir-126 mediated reduction of p85beta was accompanied by a substantial reduction in phosphorylated akt levels in the cancer cells, suggesting an impairment in pi3k signaling. 18663744_6 finally, in a panel of matched normal colon and primary colon tumors, each of the tumors demonstrated mir-126 down-regulation together with an increase in the p85beta protein level. 18663744_7 taken together, we propose that mir-126 regulates pi3k signaling partly by targeting p85beta, and that the loss of mir-126 may provide a selective growth advantage during colon carcinogenesis. 24343269_1 importantly, cellular levels of pp2a, a phosphatase, were regulated by mir155 and mir31 to fine-tune autophagy. 22406049_3 using computational and expression analysis, cox-2 was identified as a candidate target of mir-137. 22406049_4 mir-137 is able to inhibit cox-2 protein expression through directly binding to 3' utr region of cox-2 mrna. 22406049_5 reporter assay with 3'utr of cox-2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of mir-137, providing strong evidence that mir-137 was a direct regulator of cox-2. 25435430_1 mir-17 overexpression reducedcytoprotective autophagy by targeting beclin-1, whereas overexpression of mir-16 potentiated paclitaxel induced apoptotic cell death by inhibiting anti-apoptotic protein bcl-2. 26813458_1 these results suggest that mir-205 suppressed irradiation-induced autophagy by directly targeting tp53inp1. 24535747_1 moreover, we showed that mir-29a directly regulated its target protein doublecortin expression, which further modulated axon branching in primary culture. 17604720_1 to distinguish between these possibilities, we depleted hotair ncrna by rna interference in primary human fibroblasts, and determined the consequences on the transcriptional landscape of the hox loci. 17604720_2 strikingly, while sirna-mediated depletion of hotair had little effect on transcription of the hoxc locus on chromosome 12 compared to wild-type and control sirna targeting gfp, depletion of hotair lead to dramatic transcriptional activation of the hoxd locus on chromosome 2 spanning over 40 kb, including hoxd8, hoxd9, hoxd10, hoxd11, and multiple ncrnas . 26248649_2 overexpression of mir-200c led to a decrease of cdk2 protein level in both sn12-pm6 and 786-o cells . 26248649_3 conversely, inhibiting mir-200c by using antimir-200c in sn12-pm6 mir-200c and 786-o mir-200c cells led to an increase of cdk2 protein level. 26248649_4 we found that the mir-200c level was inversely correlated with cdk2 expression . 26248649_5 but there was no significant changes in cdk2 mrna level in cell lines and 30 paired tissues , suggesting that cdk2 might be negatively regulated by mir-200c at the post-transcriptional level. 26248649_6 these results strongly suggested that cdk2 was a direct target of mir-200c in the rcc cells. 17996645_1 their studies highlight the micrornas mir-34a and mir-34b/c as direct, conserved p53 target genes that presumably mediate induction of apoptosis, cell cycle arrest, and senescence by p53. 17312270_1 transfection of mcf-7 cells with pre-mir-206 or 2'-o-methyl antagomir-206 specifically decreased or increased, respectively, eralpha mrna levels.mir-206 26741129_1 these results suggest that mir-320a acts as a critical regulator of osteogenic differentiation of hmscs by repressing its target hoxa10. 26741129_2 the results of luciferase assays showed that mir-320a overexpression significantly decreased the luciferase activity of the wt but not that of the mt hoxa10 3'-utr compared to that of mir-ctl , confirming that mir-320a directly targets and downregulates hoxa10 in hmscs. 26741129_3 these results suggest that mir-320a inhibits the osteogenic differentiation of hmscs by downregulating its target hoxa10. 24535223_1 notably, overexpression of mir 21 expression was able to restore the inhibition of akt activity, downregulation of bcl2 expression and apoptosis induced by resveratrol. 25617127_1 the overexpressed ptenp1 decoyed oncomirs mir-17, mir-19b and mir-20a, which would otherwise target pten, phlpp and such autophagy genes as ulk1, atg7 and p62, indicating that ptenp1 modulated the hcc cell behavior and gene networks by mirna regulation. 25144722_1 here, we provide evidence that mir-509-5p, which is downregulated in a subset of newly diagnosed cervical cancer and hepatocellular carcinoma tissues compared with the adjacent nontumor tissue, can be activated by p53 through binding the promoter of mir-509-5p and it suppresses the growth and invasion/migration of cervical cancer and hepatoma cells by regulating apoptosis and the g1/s-phase transition of cell cycle. 25144722_2 furthermore, mdm2 was identified to be a target of mir-509-5p by targeting its 3'-utr. 25144722_3 restoration of mdm2 abrogated the cell phenotypes induced by mir-509-5p. 25144722_4 moreover, ectopic expression of mir-509-5p in hela and qgy-7703 cells repressed the expression of mdm2, subsequently enhancing its p53-activating effects. 22374218_1 expression analyses indicated that cell cycle factors mps1, cdc37, and pa2g4, and cell junction components cx43 and cldn5, are mir-133 targets during regeneration. 22374218_2 using pharmacological inhibition and egfp sensor interaction studies, we found that cx43 is a new mir-133 target and regeneration gene. 22374218_3 our results indicate that mir-133 is an endogenous inhibitor of cm proliferation through modulation of mps1 and cx43 activity. 22374218_4 these data indicate that regulatory effects of mir-133 on cm proliferation are mediated in part through mps1 and cx43 regulation. in summary, these findings implicate cx43 as a new mir-133 target and key regeneration gene. 22374218_5 zebrafish possess 4 mir-133 family members, mir-133a1, -a2, 133b and mir-133c, differing at most by 2 nucleotides in the 3' region of the mature species. 20861665_1 interestingly, herrera-merchan et al. identified two putative mir-33 binding sites in the 3' untranslated region of the p53 gene and demonstrated that mir-33 transfection represses p53 expression and p53-mediated apoptosis. 20861665_2 these results support the hypothesis that mir-33 promotes the repopulation capacity of hscs by repressing p53, and identify mir-33 as an important negative regulator of p53 that potentially promotes hsc self-renewal. 22370644_3 finally, n-cadherin was identified as a direct target of mir-145. 22370644_4 the 3'-utr element of n-cadherin messenger rna is partially complementary to mir-145. 22370644_5 these data further corroborate that n-cadherin is the direct targetgene of mir-145 in human gastric cancers. 22370644_6 figure 6. mir-145 directly target n-cadherin. 22370644_8 a total of 30 nanomoles of mir-145 precursor or mir-negative control and 30 ng pmirglo-3'-utr vector were co-transfected into cells using x-tremegene transfection reagent . 23303785_1 we verified using ago2 ip and 3'-utr luciferase reporter assays that mxd4 was indeed a direct target of mir-22 . 23303785_2 western blot confirmed mir-22 downregulated mxd4 expression at the protein level in primary human fibroblasts . 23303785_3 these results suggest the existence of a feedback loop in which myc activates mir-22 to suppress mxd4, which causes the upregulation of myc expression. 26775686_1 these data confirmed our prediction that notch1 is a putative target gene of mir-30a. 26775686_2 figure 3. mir-30a targets notch1 and si-notch1 downregulates notch1. 23277401_2 transcript levels of spl, myb, arf10, dcl1, nac1, arf8, ago1, scl and ap2, as targets of mir156, mir159, mir160, mir162, mir164, mir167, mir168, mir171 and mir172 were also quantified using the same rna preparations. 21816906_1 we report that 1,25d markedly induces expression of mir-32 in human myeloid leukemia cells, in which it targets the 3'-untranslated region of the mrna encoding the proapoptotic factor bim to reduce its expression. 26194839_2 this was further confirmed that sox9 was the target gene of mir-101. 25694452_1 moreover, overexpressed mir-1188 promoted apoptosis, enhanced caspase-3 activity, and also upregulated the expression of bax and p53. 25694452_2 mir-1188 directly targeted and negatively regulated bcl-2 and sp1. 25694452_3 silencing of bcl-2 and sp1 exactly copied the proapoptotic and anti-invasive effect of mir-1188, respectively. 25694452_4 meanwhile, the expression of apoptosis and invasion-related genes such as vegfa, fgfr1, and rprd1b was decreased following enhancement of mir-1188, as determined by gene expression profiling analysis. 25015656_2 one predicted upstream regulator was c-fos, which has two confirmed mir-155 binding sites in its 3' utr and, therefore, can be directly regulated by mir-155. 25015656_3 we established that the mir-155 mice had significantly higher levels of c-fos mrna and protein than the c57bl/6 mice at 72 h after cisplatin exposure. 25015656_4 these data indicate a role for mir-155 in the cisplatin response and suggest that targeting of c-fos could be investigated to reduce cisplatin-induced nephrotoxicity. 24736727_2 when the gscs were co-transfected with the plasmid containing short hairpin rna directed against human sh3gl2 gene and mir-330 mimic, we found that mir-330 promoted the malignant behavior of gscs by down-regulating the expression of sh3gl2. 17500590_1 we performed luciferase de-repression assays by co-transfection of the thbs1 3'utr reporter and 2'ome rnas specific to individual kshv mirnas. 17500590_2 our results demonstrate that thbs1 is targeted by multiple kshv mirnas; in particular, mir-k12-1, mir-k12-3-3p, mir-k12-6-3p, and mir-k12-11 lead to strong de-repression of the reporter. 25826085_1 our results from figure1 showed an inverse relationship between mir-34a and sirt1 in cd44+/cd24- bcscs, suggesting that sirt1 may be a target of mir-34a in bcscs. 25826085_2 as expected, forced expression of mir-34a down-regulated protein expression of sirt1 significantly . 25826085_4 these data suggest that suppressed sirt1 activity by mir-34a could reduce the population of the cd44+/cd24- bcscs. 22064652_1 the direct interaction between mir-126 and adam9 mrna was confirmed by 3' untranslated region assay. 22064652_2 on the basis of these findings, we concluded that adam9 regulates cellular migration and invasion in pancreatic cancer cells as a targetgene of mir-126. 22064652_3 to confirm that adam9 is a direct target of mir-126, we assessed the expression levels of adam9 in mir-126-transfected panc-1 or aspc-1. 22064652_4 the expression levels of adam9 in mir-126-transfected cells were decreased . 22064652_5 mutation in the seed sequence abrogated these effects which indicates the direct interaction of mir-126 and adam9 3'-utr. 22770245_1 the relative level of mir-31 to its target myf5 mrna therefore falls. 22770245_3 mir-31 targets myf5 mrna, preventing myf5 protein accumulation in the quiescent satellite cell. 22770245_4 we show that myf5 mrna, together with microrna-31, which regulates its translation, is sequestered in mrnp granules present in the quiescent satellite cell. 24398307_1 apoptosis rate and intracellular concentration of rhodamine-123 were determined by flow cytometry, the expression of multi-drugs resistant proteins mdr1 and mrp1, ercc1, rhoe, survivin and bcl-2 were determined by western blot and real time pcr. 26252635_1 our study demonstrates that the regulation of pdcd4 by mir-21 is targeted and il-6 inhibits expression of the pdcd4 gene in pc-3 and lncap cells through the targeted function of mir-21 on pdcd4. 26252635_2 pdcd4 protein expression increased after lncap and pc-3 cells were transfected with the mir-21 inhibitor , suggesting that pdcd4 is regulated by mir-21 in these prostate cancer cell lines. 26252635_3 our study also found that pdcd4 is a target of mir-21 regulation in prostate cancer cells. 23761023_1 taken together, all these results strongly suggest that cdk4 is a target of mir-124 in glioma cells. 23761023_2 these observations demonstrate that regulation of cdk4 expression by mir-124 leads to radiosensitization. 23761023_3 thus, cda-2 may exert its radiosensitizing effect on gliomacells, at least in part, through mir-124. in this research, we confirmed by a dual-firefly luciferase reporter assay that cdk4 was a target of mir-124 in glioma cells. 23761023_4 furthermore, we showed that ectopic expression mir-124 downregulated cdk4 expression, which increased the sensitivity to rt. in this study we proved that cda-2 could down-regulate cdk4 by increasing the amount of mir-124. 23761023_5 experiments in vitro and in vivo confirmed that cda-2 could increase the glioma cells sensitivity to radio-therapy through the mir-124-cdk4 axis. 25815338_1 together, these results suggest that mir-146b-3p suppresses ada2 expression by binding to the 3'-utr and that ada2 is a direct target of mir-146b-3p. 26657485_1 luciferase activation assays confirmed direct mir-142-3p-dependent regulation of the 3- -untranslated region of itgav and wasl. 26406385_1 moreover, mir-34a could directly bind to atg4b 3 - -untranslated region. 26406385_2 these results showed that mir-34a bound directly to a specific site in the 3 - -utr of atg4b mrna. 26406385_3 moreover, our data showed that mir-34a targeted the 3 - -utr sequence of atg4b mrna and modulated atg4b expression. 21441927_1 in an attempt to identify bona fide targets undergoing mir-143- dependent post-transcriptional silencing, we analysed the proteins downregulated on mir-143 overexpression for predicted mir-143 binding sites in their 3' untranslated region . 21441927_2 five proteins exhibited predicted 3'-utr binding sites for mir-143, and one of them-namely orp8-had three predicted mir-143 binding sites . 21441927_3 these data indicate that all three binding sites of mir-143 in the 3' utr of orp8 cooperatively confer repression of reporter-gene activity. 21441927_4 taken together, these approaches revealed orp8 as a target for mir-143-dependent posttranscriptional gene silencing. 26458302_2 taken together, it was concluded that mir-144 inhibited migration and proliferation in rectal cancer through the downregulation of rock1. in order to determine whether the inhibitory effects of mir-144 on the progression of rectal cancer are associated with rocks, the present study performed a series of relative experiments, and found that mir-144 inhibits the migration and proliferation of sw837 and sw1463 rectal cancer cells by targeting the crucial oncogene, rock1. 22132158_1 western blotting and 3' utr luciferase functional assays demonstrated that mir-135a down-regulated the expression of siah1 in hela cells and in mouse zygotes. 22132158_3 it was found that the siah1a protein expression was increased in both groups , confirming that mir-135a regulated the expression of siah1a. 22467200_1 luciferase reporter assay showed that mir-93 directly targeted sp7 by specifically binding to the targetcoding sequence region of sp7. 22467200_2 this showed that mir-93 regulated osteoblast mineralization by targeting sp7 and sp7 was the very important targetgene of mir-93 in osteoblast mineralization. 22467200_3 these results revealed that mir-93 posttranscriptionally repressed sp7 protein expression. 22467200_4 thus, these results suggested that mir-93 directly targeted sp7 by specifically binding with the targetcds of sp7. 22467200_7 schematic representing the putative targetsite of mir-93 in mousesp7 cds and the base-pairing of mir-93 sequences with wild-type and mutant cds regions of sp7. 26300412_1 to validate the hypothesis whether mir-497 targets insr in hepatic cells, pmir-insr-3'utr vector and pmir-mutant-insr-3'utr vector were constructed, and dna sequencing confirmed that recombinant vectors had respectively inserted wild insr 3'utr and mutant insr 3'utr these results suggested that mir-497 directly bound to 3'utr of rat insr mrna. in other words, rat insr is the target gene of mir-497. 26300412_2 among the 9 detected mirnas, only elevated mir-497 was negatively correlated with insr expression . 22908221_1 our results suggest a novel role for mir-331-3p and mir-642-5p in the control of prostate cancer cell growth via the regulation of dohh expression and eif5a activity. 22908221_2 the 182 nt element within the 3'-utr of dohh is a direct target of both mir-331-3p and mir-642-5p. 22908221_3 using bioinformatic predictions and reporter gene assays, we have identified a 182-nt element within the dohh 3- -untranslated region that contains a number of targetsites for mir-331-3p and mir-642-5p. 22908221_4 taken together, these data indicate that the 182-nt element within the 3'-utr of dohh is a direct target of both mir-331-3p and mir-642-5p. 22908221_5 taken together, these results suggest that mir-331-3p and mir-642-5p regulate dohh expression in the prostate by inducing decay of its mrna, resulting in reduced levels of dohh protein. 26191164_1 the result indicated that mir-126 suppressed the transcription activity of the pik3r2 by targeting the 3'-utr of pik3r2. 26191164_2 mir-126 repressed pi3k/akt signaling pathway by targeting pik3r2 in ec109 cell. 18077375_1 expression of a luciferase construct containing the targetsite in sufu was repressed when cotransfected with mir-378. 18077375_2 our results suggest that mir-378 transfection enhanced cell survival, tumor growth, and angiogenesis through repression of the expression of two tumor suppressors, sufu and fus-1. in the presence of the 3'-utr, the effect of sufu was repressed by mir-378 expression, resulting in high levels of cell survival, confirming that the sufu 3- utr is a target of mir-378. 18077375_3 nevertheless, without mir-378 expression , sufuutr expression exhibited higher rates of cell survival compared with sufu alone. 18077375_6 it acts on two tumor suppressors, sufu and fus-1. 18077375_7 other tumor suppressors may also be involved in mir-378 function, because mir-378 may targetmultiple mrnas. 19472311_1 finally, we tested fndc3b mrna and protein levels in hepg2 with and without mir-143 mimic transfection by way of reverse-transcription polymerase chain reaction and western blotting to determine how mir-143 acts through mrna degradation or translational repression. 19472311_2 as shown in fig.4b, fndc3b mrna levels were not significantly affected, whereas protein levels decreased substantially after treatment with mir-143. 19472311_3 these results strongly indicate that fndc3b gene expression is directly translationally suppressed by mir-143. 22891046_1 luciferase assays confirmed that mir-24 suppressed jp2 expression by binding to either of these sites. 22891046_2 in the present study, we report that mir-24, a microrna upregulated in heart failure, is an immediate upstream suppressor of jp2. in the present study, we demonstrated that mir-24 regulates jp2 expression by binding to at least 1 of the 2 sites within the 3'utr of jp2 mrna. 22891046_3 similar results were shared by the rat, mouse and human sequences, indicating that the mir-24 targeting of jp2 expression was doubly-secured through evolution. 21880462_1 our study demonstrated that mir-98 and mir-453 down-regulated tp53 expression by targeting the 3'-utr of tp53, and that cisplatin might inhibit a549 cell growth by mir-98 regulating tp53 pathway. 21880462_2 3'-utr of tp53 was regulated by mir-98/453. 21880462_4 the above results indicated that cisplatin might inhibit a549 cell growth by mir-98 regulating tp53 pathway, in which the expression of mir-34 was increased to further reduce bcl-2 expression. 21880462_5 different from precious studies, our results indicated that mir-34 and bcl-2 attend tp53 pathway in a549 cells, which was regulated by mir-98/mir-453. 21880462_6 overall, our results demonstrated that mir-98 and mir-453 down-regulate tp53 expression by targeting the 3'-utr of tp53, and also indicate that the signal factors in tp53 pathway are affected in a549 cells after mir-98 and mir-453 treatment. 22664922_1 to test whether mir-29a/b manifests its effect on bace1 due to a direct interaction, we used targetscan to predict its binding site in the mouse bace1 3' utr and create a 22 base pair mutation abolishing the mirna binding site. 22223106_4 these results demonstrate that the effect of suboptimal early nutrition and growth on both mir-483-3p and gdf3 protein is conserved between humans and rats. 22223106_5 transfection of mir-483-3p mimic significantly decreased the level of gdf3 endogenous protein , demonstrating that gdf3 expression is regulated by mir-483-3p. 22223106_6 these results demonstrate that both mir-483-3p and gdf3 mrna associate with the risc and that the binding of gdf3 mrna is dependent on mir-483-3p. 22223106_7 taken together, these data confirm the presence of a functional and direct mir-483-3p target site in the 3'-utrs of the mouse, rat and human gdf3 mrna. 23010597_3 these results indicated that mir-134 inhibits emt through regulating foxm1 expression in nsclc cells. 23010597_4 it is also shown that foxm1 is suppressed by mir-134 via direct binding to the foxm1 3'utr. 23010597_5 these results indicate that mir-134 downregulates foxm1 expression by directly targeting its 3'-utr. 21956418_2 to validate this target we evaluated the expression of cdk6 protein levels in wro, wropcdh, and wromir-191 cell clones by western blot. 21956418_3 the introduction of mir-191 significantly decreased cdk6 protein level , but not mrna , consistently with a posttranscriptional regulation of the cdk6 protein by this mirna. 21956418_4 therefore, these data show that mir-191 interferes with cdk6 mrna translation by directly interacting with both targetsequences in its 3'-utr. 21956418_5 these data suggest that the mir-191 effect is, at least in part, mediated by cdk6 targeting. 21956418_6 these results suggest that mir-191 down-regulation is correlated to cdk6 overexpression in most of the cases. 26618772_1 mir-143 directly targeted seed sequences in the 3 ' -untranslated regions of erk5. in our study, we confirmed that mir-143 expression was experimentally declined in breast cancer specimens, and erk5 was down-regulated directly by mir-143. 26618772_2 these results suggested a direct and specific interaction of mir-143 on erk5 3 ' -utr in breast cancer cells. 26618772_3 taken together, our data suggested that erk5 was a target gene of mir-143. 24750349_1 in conclusion, mir-130a is important for maintaining normal autophagy levels and promoting the survival of epc via regulation of bcl-2 and beclin1 expression, via runx3. 26298724_1 to further explore the mechanism through which mir-148a plays its antitumor role, matrix metalloproteinase-13 was identified as a target of mir-148a by western blot and luciferase reporter assay. 26298724_2 our study demonstrates that mir-148a inhibits the migration of breast cancer cells by targeting mmp-13 and also lays theoretical foundation for further exploration for the function of mir-148a. 26298724_3 furthermore, we also demonstrated that mir-148a regulated the migration of breast cancer cells by targeting mmp-13. 26298724_4 taken together, these results demonstrated that mir-148a reduced the luciferase activity of wild-type 3'-utr, but not the mutant type 3'-utr of mmp-13, suggesting that mir-148a binds to the 3'-utr of mmp-13. 26298724_5 it indicates that mmp-13 is a target of mir-148a. 23133646_1 this study reports for the first time the identification of microrna-574-5p and microrna-921 as two mirnas capable of interacting with the 39-untranslated region of the cbr1 gene and downregulating cbr1 expression. 23133646_2 hsa-mir-574-5p and hsa-mir-921 bind differentially to cbr1 3'-utr constructs. 23133646_3 we demonstrated that mir-574-5p and hsa-mir-921 both influence cbr1 protein expression in human cell lines with homozygosis for the major cbr1 1096g.a 26273410_1 by cell transfection and luciferase reporter assay, dab2 was confirmed as a direct target of mir-93. 26273410_2 subsequent experiments in vitro showed that mir-93 could promote the proliferation and migration of escc cells by targeting dab2. 26273410_3 these findings demonstrated that mir-93 could regulate dab2 expression in escc cells. in sum, these results indicate that mir-93 can directly inhibit dab2 expression by targeting its 3'-utr, and that there are more obvious changes to the dab2 protein than the mrna level when transfection with mir-93 is performed, suggesting that mir-93 regulates dab2 expression mainly by translational suppression. 21252116_1 interestingly, we also observed a concomitant decrease in expression of the let-7 mirna targetimp-1 by 73%, and cdc34 and total ras, by 30% and 16%, respectively, compared with control cells , suggesting let-7 regulation by c-myc. 21252116_2 however, qrt-pcr showed an increase in both mature let-7a and let-7b mirna expression , suggesting that c-myc modulates expression of known let-7 target, imp-1, cdc34, and ras, in part by negatively regulating endogenous mature let-7 mirna levels in human colon cancer cells. 18801740_1 here we provide evidence in ad brains of a specific up-regulation of an nf-kb-sensitive mirna-146a highly complementary to the 3' un-translated region of complement factor h , an important repressor of the brain's inflammatory response. 18801740_2 up-regulation of mirna-146a coupled to down-regulation of cfh was observed in ad brain and in il-1ss, ass42 and/or oxidatively-stressed human neural cells in primary culture. 18801740_3 transfection of hn cells using an nf-kb-containing pre-mirna-146a promoter-luciferase reporter construct in stressed hn cells showed significant up-regulation of luciferase activity that paralleled decreases in cfh gene expression. 18801740_5 incubation of an antisense oligonucleotide to mirna-146a was found to restore cfh expression levels. 18801740_6 these data indicate that nf-kb-sensitive mirna-146a-mediated modulation of cfh gene expression may in part regulate an inflammatory response in ad brain and in stressed hn cell models of ad, and illustrates the potential for anti-mirnas as an effective therapeutic strategy against pathogenic inflammatory signaling. 22883469_1 mir-133b target egfr by binding to the egfr 3'-utr. 22883469_2 bioinformatic analysis and luciferase reporter assay revealed that mir-133b can interact specifically with the 3'-utr of egfr mrna. 22883469_4 these data suggest that mir-133b directly inhibits egfr expression via its 3'-utr. 22883469_5 in pc-9 cells, which are egfr-addicted lung cancer cells, egfr mrna was significantly downregulated by transfection with mir-133b mimic. 22883469_6 additionally, the egfr level was measurably reduced by mir-133b mimic and increased by mir-133b inhibitor . 22883469_7 these data show that endogenous egfr expression was regulated by mir-133b. 25465153_1 therefore, these results suggest that mir-96 regulate the level of reck by combining with predicted site of the reck 3'-utr sequence and reck is a direct target of mir-96. 25465153_2 these data suggested that overexpression of reck inhibited the effect of mir-96 on ec. 25209900_1 mir-451 is decreased in hypertrophic cardiomyopathy and regulates autophagy by targeting tsc1. 25849652_1 programmed cell death 4 is known to be up-regulated during apoptosis as a functionally important target of mir-21 . in pbmc after mir21-i injection, pdcd4 expression was increased in bd mice. in addition, the expression levels of rhob, pd-1, and il-12p35 were also increased in bd mice. 25849652_2 rhob is known as a target of mir-21 . 25849652_3 the mrna expression of rhob is consistently up-regulated after mir21 inhibition in bd mice. 19359473_1 we identify src homology-2 domain-containing inositol 5-phosphatase 1 as a direct target of mir-155. 19359473_2 among the target was ship1 , a gene that is repressed by mir-155 and which has a conserved 8-mer target "seed" in its 3'-utr . 19359473_3 to directly test whether mir-155 can repress ship1 through direct 3'-utr interactions, we cloned the 3'-utr of ship1 into a reporter plasmid downstream from luciferase and performed reporter assays using 293 t cells. 19359473_4 these data reveal that mir-155 directly target the ship1 3'-utr leading to repressed expression. 24314651_1 we investigated how expression of human papilloma virus type-16 onco-proteins e6 and e7 affected expression of mir-24 and mir-205 during proliferation and differentiation of hfks. 24314651_2 we show that the induction of both mir-24 and mir-205 observed during differentiation of hfks is lost in hfks expressing e6 and e7. 26170028_1 to validate that mir-148a and mir-30a induce their suppressive effects on tip47 by directly binding to its 3'utr, wild type or mutant binding regions of mir-148a or mir-30a were cloned downstream of luciferase reporter gene in pmirglo vector. 26170028_4 similarly, mir-30a mimics suppressed luciferase activity in cells harboring wild type mir-30a vector but not the mutant type. 26170028_5 mir-148a and mir-30a mimics suppressed tip47 mrna and protein expression compared to untransfected cells. 24577056_1 transfection of mir-214, mir-363*, mir-326, mir-940, mir-29c, mir-665, mir-34b*, mir-708, mir-601, mir-124a, mir-380-5p, mir-885-3p and mir-593 significantly inhibited the luciferase activity of the construct containing the b7-h3 3'-utr compared with scrambled mirna-transfected controls , indicating that these mirnas directly bind to the b7-h3 3'-utr. 17569667_2 fig. 3 shows that the presence of mir-221, mir-222, or mir-221 and mir-222 in tandem strongly affected luciferase expression , measured as relative luciferase activity. 17569667_4 these data strongly support the hypothesis that mir-221 and mir-222 post-transcriptionally regulate p27kip1 expression in lncap and 22rv1 cells. 17569667_5 the results that we collected by both the overexpression and the knock down of mir-221 and/or mir-222 converge toward the identification of p27 as an actual target of mir-221/mir-222 in lncap, 22rv1, and pc3 pca cell lines. 17569667_6 these results support the bioinformatic prediction indicating the 3'-utr of p27 mrna as a targetfor mir-221 and mir-222, and denote that the two matching sites thus identified strongly contribute to the mirna-mrna interaction mediating the post-transcriptional inhibition of the expression. 24938872_3 in accordance with bioinformatics and luciferase activity analyses, cul1 was found to be the direct target of mir-203. 24938872_4 furthermore, mir-203 inhibition and cul1 overexpression reversed the cytotoxicity of azd6244 on the mda-mb-231 and hcc1937 cells. 26845432_1 the overexpression of mitf could counteract the biological effect of mir-137 in multiple myeloma cells. 26845432_2 we conclude that mitf is a direct target of mir-137. 26845432_3 a dual luciferase reporter gene analysis revealed that mitf is a direct target of mir-137. 26845432_4 the mir-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-met expression and further decreasing the akt phosphorylation via targeting mitf. 26729468_1 we found that expression of mir-125b was significantly inhibited in uremic rats coupled with increased cyp24 at both protein and mrna levels compared with normal controls. 26729468_2 in nrk-52 kidney cells, we further found that mir-125b antagomirs increased cyp24 but mir-125b mimics decreased cyp24, and luciferase assay confirmed that cyp24 is a direct target of mir-125b. 26729468_3 these results further support that mir-125b directly regulates cyp24 in kidneys. 26729468_4 taken together, the data suggest that cyp24 is a direct target of mir-125b. 26859141_1 specifically, we showed that cxcl8/il8, uhrf1, mcm10, and cdkn3 were downregulated and targeted by mir-146a-5p. 26859141_2 the interaction between mir-146a-5p and their targets cxcl8 and uhrf1 was validated in cell culture experiments. 26859141_4 the transfection with mir-146a-5p significantly reduced the concentration of secreted cxcl8/il8 protein from both cell lines whereas the inhibition of mir-146a-5p increased the amount of secreted cxcl8/il8 measured by elisa . 26859141_6 transfection with mir-146a-5p significantly reduced the amount of uhrf1 in both cell lines, however, a treatment with mir-146a-5p inhibitor showed no effect on uhrf1 expression . 26513420_1 the overexpression of mir-135 suppressed hoxa2, whereas the knockdown of mir-135 promoted hoxa2 expression.taken 26513420_2 together, our data suggested that hoxa2 expression was negatively regulated by mir-135. 20837890_1 we further identified that 3 proapoptotic proteins and 2 antiapoptotic proteins were authentic targets for mir-494. 23770100_1 as shown by luciferase reporter assay, mir-142-5p bound directly to the 3 ' -untranslated region of btg3. 23770100_3 these results suggested that btg3 is a candidate target gene of mir-142-5p in vsmcs. 23770100_4 we obtained evidence in the present study that btg3 mrna and protein expression are down-regulated by mir-142-5p. 26269764_2 knockdown of hk2 recapitulated the effects of mir-143 and accompanied with decreased glucose metabolism. 26269764_3 taken together, above results indicate that hk2 is the downstream target of mir-143 in prostate cancer. 26269764_4 taken together, these results suggest that mir-143 down-regulates hk2 to suppress tumor growth in prostate cancer. 26622652_1 the results showed that mir- 182 specifically targets the gene encoding neuritin, nrn1, as demonstrated by a reduction in the protein and mrna levels of nrn1. 26622652_2 these data suggest that exogenous mir-182 downregulates nrn1 expression. 20673990_1 we further demonstrate that lincrna-p21 binds hnrnp-k. 20673990_2 consistent with a bona fide interaction, we observed a greater and very significant enrichment of lincrna-p21 in the hnrnp-k rip relative to the igg control rip with two hnrnp-k different antibodies . 20673990_3 together,the rna pull-down,native rip,cross-linked rip and deletion mapping results demonstrate a specific association between hnrnp-k and lincrna-p21. 26895471_1 additionally, we discovered that prkd1 expression was negatively regulated by mir-34a binding to the prkd1 3'-utr. 19683563_2 a western blot performed on the same cells showed that bcl2 protein was clearly reduced in the stable transfection cell line of mir-34a, as compared to cells transfected with the control vector . 19683563_3 the luciferase reporter assays directly support the hypothesis that mir-34a regulates bcl2 through at least one mirna recognition element in the 3'utr of bcl2. 26476938_1 these data demonstrated that mir-24 interacts directly with the predicted binding site of the fasn mrna in gmec. 23418453_2 data suggests that, in addition to possible antitumor effects, treatment of hcv-infected huh7.5 cells with ifn-alpha upregulates mir-130a/301 thereby reducing c-met expression and hcv pathogenesis. 23100280_1 mir-34b expression decreased by 75% compared to the negative control , whereas creb levels were increased in addition to creb target genes known to influence myeloid leukemia . 23100280_2 since decreased mir-34b expression can affect creb expression, we examined the clonogenic properties in methylcellulose colony assays. 23100280_3 enhanced colony formation was observed in the mir-34b knockdown human fetal liver cells compared to the scrambled mir-target . 23100280_5 these experiments suggest that mir-34b is a tumor suppressor in aml principally by inhibiting creb expression. 17363372_1 we cloned the 3'-utr of tpm1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. 17363372_2 to determine the role of the mir-21 binding site in regulating its expression, we deleted the mir-21 binding site in variant 1 . 17363372_4 3f, neither mir-21 nor anti-mir-21 had any effect on the luciferase activity, highlighting the importance of this mir-21 binding site. 17363372_5 therefore, these results suggest that the mir-21 binding site present in the tpm1-utr region is critical for mir-21-mediated regulation at the translational level. 17363372_6 thus, even though the mir-21 binding site is away from the gfp , it is still functional. 17363372_7 this result further indicates that tpm1 is a mir-21 target 21233447_1 the no-dependent regulation of mir-200 family suggested a role for these mirs during mes commitment to mesendoderm. 21233447_2 to verify this hypothesis, 2 representative mir-200 family members with different seed sequences, mir-200a and mir-429, both of which are able to target sip1/zeb2 mrna, were overexpressed, at high and low copy numbers, as pre-mirs in undifferentiated mes. 26899994_1 we also reported for the first time that mir-155 targets calcium-regulated heat stable protein 1 , which regulates the stability of tumor necrosis factor alpha mrna. 26899994_2 western blot results revealed that overexpressed mir-155 also inhibits carhsp1 protein expression . 26899994_3 furthermore, the qrt-pcr results indicate that the mrna levels of carhsp1 are downregulated by overexpressed mir-155 . 26899994_4 all these results indicate that carhsp1 is a functional target of mir-155, which directly targets its 3'-utr, and that carhsp1 serves as a mediator of mir-155 by regulating the production of tnf-alpha and thereby affecting foam cell formation. 24931256_4 the luciferase activity of reporters driven by igf1r and bcl2 3'-untranslated regions in sgc7901/ddp cells suggested that igf1r and bcl2 were both direct target genes of mir-503. 19408243_1 we identified a functional targetsequence for mir-31 in the 3' untranslated region of foxp3 mrna. 19408243_2 these results demonstrate that foxp3 expression is inversely proportional to mir-31 expression level. 17600087_1 let-7 regulates hmga2 expression in ovarian cancer and predicts disease progression. 26081366_1 after transfection by mir-129 mimics or inhibitor, both of a549 and spca-1 cells showed weaker band or stronger band of vcp protein, respectively, by western blotting. 26081366_3 after deletion of one or both of the two putative mir-129-binding sites, the luciferase activities rose remarkably , suggesting that mir-129 directly regulates vcp gene through these two binding sites. 18379589_1 immunoblot and immunofluorescence analyses showed that overexpression of let-7b in melanoma cells resulted in significant downregulation of cyclins d1, d3, and cdk4 protein expression. 18379589_3 moreover, the negative regulatory effect of let-7b on cyclin d1 expression was indeed mediated through binding to 3'-utr of thetarget, as shown by in vitro luciferase assays.let-7b 24249224_1 apoptosis during tgf--beta signaling, where sirt1 and sp4 are suppressed by mir-34a-5p and mir-34a-3p, respectively 23145124_1 these results indicate that mir-124a, mir-1669, mir-1710 and mir-1782, influence ahcyl1 expression in vitro via its 3'-utr which suggests that post-transcriptional events regulate or influence ahcyl1 expression in the chick oviduct. 26045772_1 these results strongly suggest downregulation of mir-98 led to il-6 overexpression via direct binding to putative binding site in the il-6 3'-utr region during cm or mcp-1 induction in thp-1 cells. 21670079_1 the inverse expression of mir-193a with both plau and k-ras is consistent with these genes being relevant targets during transformation. 21670079_2 sequence complementarity between mir-193a and the 3- utrs of plau and k-ras, with the 8 nt seed sequence shown as a gray box. 21670079_3 luciferase activity of reporters containing the 3'-utr of plau or k-ras 24h after transfection with mir-193a or mir negative control. 21670079_4 d, plau or k-ras mrna levels in the indicated breast cancer cell lines transfected with mir-193a or control mirna. 19924305_1 by this method we identified antisense to marcks related protein , whose family member marcks is a target of mir-21, a microrna involved in tumor growth, invasion and metastasis in multiple human cancers. 17322030_2 translocations generate a truncated hmga2 mrna lacking the let-7 complementary sites of the wild-type mrna and are associated with the indicated tumors. in its 3'utr, human hmga2 has seven let-7 complementary sites, all of which are conserved in the mouse, rat, dog, and chicken. 22179046_1 employing an experimental strategy similar to that described above, we could show that mmp9 and emilin2 are directly regulated by mir-320 through their 3' utr target sequences . 22179046_2 these results are consistent with a dual mechanism for the regulation of mmp9 expression that involves transcriptional control by ets2 and posttranscriptional control by mir-320. 26450567_1 on the one hand, 3- -untranslated region reporter analysis revealed a mir-136 binding site in the 3- utr of il-6. 26450567_2 together these results indicated that cellular il-6 expression was greatly enhanced following transfection with either plasmid-expressed mir-136 or mir-136 mimics. 26117336_1 these data suggest specific binding of mir-17/20a with the dapk3 mrna. 26117336_2 these data suggest that mir-17/20a targets dapk3 in the cds region to suppress its translation. 26754824_1 mir-133 was identified to directly bind to evi1 to regulate it. 26754824_2 this indicates that mir-133 promoted apoptosis in the presence of adr in evi1-high-expressing hel leukemic cells. . in summary, we identified mir-133 as a mirna that regulates evi1, whose overexpression is associated with a poor prognosis in aml. 23200854_1 mir-155 promotes ifngamma expression by cd4+ t cells through a mechanism involving repression of ship1. 23200854_2 however, the partial recovery of the ifngamma phenotype following ship1 knockdown indicates that addition targets of mir-155 are also involved in this phenotype. 20622002_1 luciferase assays using constructs containing junb 3'-untranslated region with wild type or mutated mir-663 targetsites provided strong evidence that mir-663 target junb 3'-utr directly . 20622002_2 together, these results establish mir-663 as a new regulator of junb and jund levels and more generally of ap-1 activity. 20622002_3 it might be that 663-i could also impair the targeting of transcripts encoding some unidentified repressor of junb by mir-663. 23755189_2 consistent with a role for the mir-30 family in smoothened modulation a 54% reduction was seen in the gfp-smo+mir-30 embryos when compared to embryos injected with the gfp mrnas alone, indicating an interaction between smoothened 3'utr and mir-30. 23755189_3 these features are a result of direct targeting of the hh transmembrane receptor smoothened by the microrna family, representing a novel role for mir-30 in muscle fibre specification and distribution. 19286996_1 mir-184 negatively effects nfat1 protein synthesis. 19286996_2 here we provide evidence that a specific microrna, mir-184, inhibits nfat1 protein expression elicited by ucb cd4+ t cells. 19286996_3 to determine whether manipulation of nfat1 protein levels through interference with the activity of mir-184 is sufficient to result in an increase in transcription of nfat1-targetgenes, the transcription of il-2, a gene strongly activated by nfat1 binding to its promoter after stimulation,14 was assayed by qrt-pcr. 19286996_4 these findings indicate that mir-184 interference with nfat1 in ucb cd4+ t cells is indeed sufficient to influence both nfat1 protein levels and transcription of the known nfat1 target gene, il2. 23155233_2 high mir-34a expression level in the cells after irradiation at 60 gy reduced the p53 expression level. 22447776_2 furthermore, the arpc5 3'-utr is predicted to contain binding sites for mir-22/883a-5p. 22447776_3 consistent with this, we show that mir-22/883a-5p-搈ediated regulation of arpc5 is critical for controlling the expression of genes known to be involved in chromatin remodeling during haploid germ cell differentiation. 22447776_5 4, mir-22/883a-5p-搕argeted arpc5 interacts with mrna and mediates translational suppression. 26170936_1 in addition, the results of the western blot analysis demonstrated that inhibition of mir-375 expression in c2c12 cells significantly enhanced the protein expression levels of runx2 . 26170936_2 these results demonstrated that mir-375 downregulated the expression of runx2. 26170936_3 these results indicated that mir-375 inhibited osteogenic differentiation, in part via the downregulation of runx2 expression. 22197821_1 the expression levels of these target in the assay were 61% for fgfr2 of that of un- treated huvecs , which confirmed that mir-19b-1 actually down-regulated important factors in the growth signaling pathway. 22197821_4 figure s3 mir-19b-1 target cyclin d1 protein translation. 26902416_1 together, these results indicated that ldha was a direct downstream target of mir-34a in breast cancer cells. 26584294_1 tbk1 was identified as a potential target gene of mir-203, with the predicted binding site at the base from positions 526 to 531. 26584294_2 tbk1 is a noncanonical ikappab kinase family member and plays a vital role in cell survival and tumor growth. 26584294_3 to validate whether the 3'-utr of tbk1 is a functional target of mir-203, a dual-luciferase reporter system was employed.data 26584294_4 from the luciferase assay showed that overexpression of mir-203 remarkably suppressed the luciferase activity of the reporter gene with the wild-type construct but not with the mutant tbk1 3'utr construct in os cells. 26584294_5 our results suggest that tbk1 is a direct target of mir-203 in os cells. 21454583_1 mir-205 significantly suppressed the luciferase activity of reporter plasmids containing the 3'-utr sequences complementary to either e2f1 or e2f5. 21454583_2 overexpression of mir-205 in melanoma cells reduced e2f1 and e2f5 protein levels. 23285103_1 the specificity of the binding of the 3'-utr of cdh5 gene with mir-142a-3p duplex was investigated by microinjecting gfp- cdh53'-utr mrna, in the presence and absence of mir-142a-3p duplex and a sequence unrelated mir-144 duplex. 23285103_2 zebrafish embryos sequentially injected with gfp- cdh53'-utr mrna and mir-142a-3p duplex showed suppression of gfp expression, while mir-144 duplex had no effect on the gfp expression . 23285103_3 this suggests that the 3'-utr of cdh5 specifically interact with mir-142a-3p. 22989374_1 the high-ranking genes cdc42, cdh1, pak2, bcl-2, and mapk1 were confirmed as important targets of mir-224 and involvement in hepatocarcinogenesis. overexpression of mir-224 significantly in hek293 and huh7 cells altered the expression levels of cdc42, cdh1, pak2, and bcl-2 at both mrna and protein levels. 19841744_2 our results showed a negative correlation between the expression of let-7c and tgfbr1 during liver development, when the first was expressed higher in the adult liver compared to embryonic liver , and the second was expressed vice versa . 19841744_3 taken together, these results show that tgfbr1 is a plausible direct target of let-7c. 25705792_2 as observed for cxcr4, traf6 mrna level decreases during the first hours of activation of cd4镁 t cells, then remains at a lower level later in culture , decreasing slightly at 48 hours , whereas the decrease of mir-146a may unblock traf6 mrna translation and then increase traf6 protein expression level in these cells . 23752207_1 luciferase reporter assays revealed a 2.3-fold inhibition of expression due to interaction of mir-142 with the sirt1 3'-utr, mutation analysis revealed that only the mir-142-5p target site was active. 23752207_3 this finding conclusively proved that sirt1 is a bona fide mir-142-5p target, corroborating our mir-142-5p overexpression and inhibition studies described previously. 23752207_4 in addition, we provide conclusive evidence that sirt1 is a direct mir-142-5p target. 26596830_2 taken together, our results demonstrate that runx2 was a direct target of mir-30a. 17462020_1 symr is encoded in cis to an sosinduced gene whose product shows homology to the antitoxin maze . 17462020_2 synthesis of the syme protein is tightly repressed at multiple levels by the lexa repressor, the symr rna and the lon protease.syme 23082062_2 mir-519a and ribosomal protein s6 kinase polypeptide 3 were predicted as the most significant candidates by mirna-mrna network. in addition, cyclin d3 and clathrin heavy chain , usually up-regulated in hcc tissues, were validated as the direct target of mir-138 and mir-199a-5p, respectively. 25040912_2 the mir-302b-reduced e2f3 levels were also identified to be associated with atra-mediated glioma cell death. 20186779_1 in one iranian family segregating autosomal recessive non-syndromic hearing loss , we identified a homozygous variant in a predicted mir-96/182 binding site in the 3'utr of the rdx gene. 20186779_3 to determine whether the predicted mir-86/182 binding site in the rdx 3' utr is a biologically relevant target of regulation we performed luciferase assays . 26314506_1 additionally, we confirmed that mir-335 can directly target grm4, which can further regulated the expression of mir-335. 26314506_2 antidepressant drug treatment with citalopram can upregulate mir-335 expression and downregulate grm4 expression. 26314506_3 these lines of evidence collectively demonstrated that mir-335 recognizes and regulates grm4 mrna through specific binding to its 3' utr. 25481483_1 mir-210 up-regulation inhibits proliferation and induces apoptosis in glioma cells by targeting sin3a. 25481483_2 aberrantly expressed mir-210 regulates human u251 glioma cells apoptosis and proliferation partly through directly down-regulating sin3a protein expression. 24356567_1 our results demonstrate that overexpression of mir-145 inhibits tumor growth in part by targeting c-myc. 24356567_2 all of these results document that mir-145 represses c-myc expression, which in turn inhibits the growth and tumorigenicity of escc cells. 24356567_3 therefore, these results highlight the significance of mir-145 as a tumor suppressor in escc growth in part by targeting c-myc. 20966935_1 we further demonstrate that the mir-30 family directly controls bcl-6 expression and mir-9-1 and let-7a directly control prdm-1 expression through targeting their 3'utr, mediating the fdc effect. 20966935_2 to examine whether bcl6 was regulated by mir-30, we ectopically expressed each of the mir-30 family members in su-4 and ramos cells by lentiviral transduction. 20966935_3 overexpression of mir-30 family members resulted in a dramatic decrease in expression of bcl6 protein compared with a scrambled control . 20966935_4 as shown in figures 3c-e, depletion of mir-30 expression by anti-mir-30s abolished fdc-induced bcl6 downregulation, indicating that the mir-30 family was required for regulation of bcl6 expression by fdcs. 21878650_1 cotransfection studies with 3'-utr of these genes and mirna mimics have demonstrated that bcl2 is a direct target of mir-497 and that ccnd2 is regulated negatively by either mir-302b or mir-497. 21878650_2 overexpression of either mir-497 or mir-302b reduced expression of their identified target genes and increased caspase 3-mediated apoptosis of sh-sy5y cells. 26179263_1 expression of adam9 mrna and mir-203 were reversely correlated in hcc samples as calculated by pearson correlation.hulc 26179263_3 mir-203 expression levels were reduced in hcc cell lines than in lo2, especially in huh7 cells . 26179263_4 adam9 and hulc were more abundant in huh7 than in other cell lines. 26179263_5 we found that mir-203 inhibitor enhanced adam9 at mrna and protein levels in plc cells. in contrast, mir-203 mimic inhibited the expression of adam9 at mrna and protein levels in huh7 cells. in addition, we found that the expression of hulc in hcc cells transfected with mir-203 mimic was significantly downregulated, whereas mir-203 inhibitor markedly increased hulc level in hcc cells comparing with nc cells . 26179263_6 these results demonstrated that mir-203 had a negative regulatory effect on adam9 or hulc. 26867589_1 the 3'-utr of pdcd4 contains three binding sites for mir-499 and one for mir-21. 26867589_2 in tonsillar sccs samples, both mir-21 and mir-499 were elevated but the rna levels for pdcd4 was markedly lower. 26867589_3 we also transiently transfected scc003 cells with pdcd4 with and without the 3'-utr, and as expected, pdcd4 mrna expression was downregulated by both mir-21 and mir-499 only when the 3'-utr was present . 26867589_4 taken together these observations suggest that mir-21 and mir-499 can both regulate the expression of pdcd4. 25939439_1 identification of mir-137 as a regulator of ezh2 via binding to ezh2 3'-utr. 25939439_2 these findings indicate that ezh2 is a direct downstream target for mir-137 in gbm cells. 21383689_1 we further identified the embryonal carcinoma antigen podocalyxin-like protein 1 , an anti-adhesive protein expressed in aggressive tumors, as a target of mir-199a-5p. 21383689_2 we identified podocalyxin-like protein 1 as a target of mir-199a-5p. 21383689_3 these data show that mir-199a-5p regulates podxl through a conserved binding site in its 3'-utr. 21844895_1 to confirm whether ppar-gamma is a direct target of mir-27b, we performed luciferase reporter assays in hek293 cells. 21844895_2 cotransfection of mir-27b with the luciferase reporter gene linked to the wild-type 3'-utr of ppar-gamma strongly inhibited the luciferase activity, while cotransfection with anti-mir-27b rescued this effect . 21844895_3 we further measured the ppar-gamma expression level in smad4 mutant heart tissues, which showed increased mir-27b levels, and observed that ppar-gamma was significantly decreased in smad4 mutants . 21844895_4 consistently, ppar-gamma levels were significantly reduced in mir-27b transgenic hearts . 21844895_5 figure 6 ppar-gamma is a target of mir-27b in cardiomyocytes. 21844895_6 all these observations suggest that mir-27b acts as a negative regulator of ppar-gamma at post-transcriptional levels, and ppar-gamma mediates the cardiac hypertrophic effect of mir-27b. 26305546_1 indeed, bioinformatic searches indicate that hdac4 are predicated to be putative mir-29a targets. 26305546_2 moreover, mir-29a overexpression significantly downregulated hdac4 immunoreactivity in mir-29atg mice with cholestasis compared with the wt littermates , indicating that mir-29a might have an impact on hdac4 expression in early cholestasis. 26305546_3 hscs of mir-29atg mice could significantly reduce the upregulation and nuclear translation of hdac4 in response to tlca stimulation in hscs . 25304362_1 the results showed that mir-134 expression levels increased in primary cultured neuronal cells and mouse brain from 12h to 7 day reoxygenation/reperfusion after 1h ogd or 1h mcao treatment. 25304362_2 mir-134 overexpression promoted neuronal cell death and apoptosis by decreasing hspa12b protein levels. 26227241_1 figure 4: regulation of slc11a1 and lilr-like by mir-214. 26227241_2 figure 5: regulation of vav2 by mir-331-3p. 26227241_3 these results may indicate that similar responses are happening in the host during salmonella infection, that is, the down-regulation of mir-214 may allow for increased expression of slc11a1 and lilr-like during salmonella infection, and up-regulation of mir-331-3p expression may inhibit expression of vav2. 22232426_1 luciferase assays indicated that mir-34a and mir-449a were less effective in regulating a variant than the wildtype hnf4a 3'-utr. 22232426_2 hnf4a protein expression was down-regulated by hsa-mir-449a, hsa-mir-34a, and the positive control hnf4a sirna . 22232426_3 compared with the negative control mirna , hsa-mir-34a and hsa-mir-449a reduced the pis-hnf4a luciferase activity by 25 and 28%. 26565624_1 more importantly, hoxb1 was shown experimentally to be a direct target of mir-3175 in this study. 26565624_2 in this study, we suggest that hoxb1 functions as a tumor suppressor gene in glioma and that the expression of hoxb1 is regulated by mir-3175. 26565624_4 in this study, hoxb1 was shown experimentally to be a novel target of mir-3175. 26111662_1 further, overexpression of hsa-mir-218 mimics suppression in protein levels of ptpa , suggesting that mir-218 directly targeted ptpra. 26111662_2 the application of anti-mir-218 restored and mir-218 mimics suppressed the levels of ptpa resulting from era or erb overexpression , suggesting that era and erb differentially regulated ptpa through mir-218. in our study, mir-218 specifically targeted the 3'-utr of ptpa, the gene for ptpa, and regulated the tyrosine phosphorylation of gsk-3b and pp2a. 21532345_3 interestingly, two genes that were significantly downregulated were the lncrna neat-1 and a protein coding gene pspc1. 26079880_1 this indicates that mir-139 may suppress the expression of top2a through the binding sequence on its 3'utr region. 26079880_2 to further confirm that top2a is negatively regulated by mir-139, we used a lentiviral delivery system to overexpress mir-139 in tumor cells. 26079880_3 these results suggest for the first time that top2a is a directlynovel targetof mir-139 in luminal type breast cancer cells. 25725784_1 mice microglia cell lines were transfected with mir-204 mimics and inhibitors or treated with resveratrol, and the effects on cell growth, proliferation, and apoptosis of cells were assessed. 25725784_2 lps induced inflammation and activation of mice microglia. 25725784_3 through overexpression of sirt1, resveratrol, and inhibitor of mir-204 inhibited inflammation process, proliferation of mice microglia cells and promoted its apoptosis. 25725784_4 we identified if resveratrol and mir-204 could repress inflammation process and proliferation of mice microglia cell through promoting the expression of sirt1. 25928008_1 mir-148a targets hotair in breast cancer cells 25851994_1 our results reveal that mir-107 is an upstream regulator for siah1 down-regulation in human breast cancer cells and mir-107 provides a potential effective target for the treatment of tnbc. 25851994_2 our current results demonstrated that mir-107 directly down-regulated siah1 expression in human breast cancer cells. 25851994_3 our result also showed that mir-107 down-regulates siah1 expression by directly binding to its predicted sites in the 3'-utr of siah1 in mcf-7 cells . 20542134_1 the results showed that mir-146a mimics obviously decreased the mrna levels of irak1 and traf6 . 20542134_2 furthermore, overexpression of mir-146a resulted in the down-regulation of the protein levels of irak1 and traf6, while mir-146a inhibitors had no obvious effect on the targetproteins . 20542134_3 taken together, above data suggest that irak1 and traf6 are potential target of mir- 146a in gastric epithelial ges-1 cells. 22386953_3 our study identified for the first time that ar is posttranscriptionally regulated by mir-124a in thyroid cancer tissues. in other words, those cases that had an inconsistency between ar mrna with ar protein had a positive correlation with mir-124a, suggesting a possible role of mir-124a in regulating the posttranscriptional processing of ar. 22386953_4 testosterone was not able to restore the inhibitory effect of mir-124a on ar luciferase activity, while it reversed the inhibitory effect of flutamide, suggesting that mir-124a is more efficient in inhibiting ar than flutamide. 20935678_1 taken together, these results suggest that tp53 is an authentic target of mir-25 and mir-30d in 293t cells. 20935678_2 we introduced these p53 constructs and mirnas into human lung adenocarcinoma p53-null h1299 cells and found that both mir-25 and mir-30d down-regulated the expression of the ectopic p53 gene with a wt 3'-utr . 20935678_3 these results suggest that mir-25 and mir-30d regulate cellular senescence through down-regulating p53 expression and subsequently the expression of p21 and that such regulation depends on mirna binding sites of tp53 3'-utr. 20935678_4 taken together, these data suggest that dysregulation of mir-25 and mir-30d is pathologically important to p53 function in h929 cells. 25470111_2 ctnnd1 was proved to be a direct target gene for mir-145. 25470111_3 besides suppressing cytoplasmic ctnnd1 expression, mir-145 could recover the membranous localization of ctnnd1 and e-cadherin. 26163260_2 and targetscan were used and identified a conserved mir-503-binding site in the 3'-utr of prmt1 mrna. 26163260_4 these data indicate that prmt1 is one of the direct targets of mir-503 in hcc. 26163260_5 mir-503 mimics markedly increased the expression of mir-503, and mir-503 inhibitors markedly increased the expression of mir-503 expression. 26163260_6 these results demonstrated that prmt1 is a direct target of mir-503 in hcc cells. 26189788_1 mir-let-7f targets cyclin d1 while mir-138 targets cyclin d3. 26189788_2 fig. 5. post-transcriptional repression of cyc d1 and cyc d3 by mir-let-7f and mir-138. 23568502_1 inhibited mir-155 expression by transfection with mir-155 inhibitors reduced proliferation and promoted apoptosis of mcf-7 cells. 23568502_2 moreover, tp53inp1 is one of the targets of mir-155. 22353043_1 and over-expression of mir-21 in u251 cells abolished the enhancement of pdcd4 protein by ua. 22915757_1 here, we report that the metastasis-associated microrna mir-10b directly binds the 3' untranslated region of micb and downregulates its expression. 22915757_2 as can be seen in fig.2b, a moderate, yet significant decrease in luciferase activity was observed in the presence of mir-10b, whereas the mutations in the 3'utr of micb abolished this effect, indicating that mir-10b indeed directly target micb at the predicted binding site. 22915757_3 therefore, we concluded that mir-10b specifically controls micb expression. 22915757_4 thus, we concluded that targeting of micb by mir-10b leads to a specific reduction of micb expression and consequently to reduced killing by nk cells. 26250158_1 taken together, these results suggest that pld1 is a potential target gene of mir-638 in gc. the protein levels of pld1 were determined by western blotting in mkn-45 and sgc-7901 cells transfected with mir-638 mimic, mir-638 inhibitor or the corresponding nc. 26250158_2 beta-actin served as an internal control. in line with these results, the endogenous pld1 protein level was also decreased in mir-638-overexpression gc cells and could be restored in mir-683-depleted gc cells . 14744852_1 taken together, these data indicate that, during prolonged hypoxia, hif-alpha proteins negatively regulate hif-1alpha expression through an increase in ahif and destabilization of hif-1alpha mrna. 14744852_3 binding of ahif to the hif-1alpha mrna 3'-utr could expose au-rich elements present in the hif-1alpha mrna 3'-utr and thus possibly increase the degradation speed of hif-1alpha mrna . 14744852_5 the maximal induction of the ahif transcript by hypoxia occurred before any decrease in hif-1alpha mrna levels. 23355465_1 taken together, the results showed that mkk4 is a new target of mir-92a and that endogenous mkk4 can be directly regulated by mir-92a in macrophages during pathogen-associated molecular pattern stimulation. 23355465_2 these results showed that the expression of tnf-alpha and il-6 was significantly enhanced by mir-92a inhibitors and that this effect could be blocked by mkk4 knockdown . 25505154_1 quantitative nuclear proteomics identifies that mir-137-mediated ezh2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells. 20473940_1 mir-137 could significantly suppress cdc42 3' utr luciferase-reporter activity, and this effect was not detectable when the putative 3' utr targetsite was mutated. 20473940_2 as shown in figure 4, compared with the negative control, transient expression of mir-137 led to a significant decrease in cdc42 protein and mrna expressions , similar to that caused by transfection of si-cdc42 in both cell lines. 20473940_3 taken together, these data suggest that the 3' utr of cdc42 is a functional targetsite for mir-137 in the colorectal cancer cells. 20473940_4 these data suggest that mir-137 negatively regulates invasion of the colorectal cancer cells, and this may, at least in part, be due to its targeting effect on cdc42. 26142856_3 overall, increased presence of mir-24 in the extracellular environment leads to higher expression of mir-24 within embryos and results in decreased expression of a mir-24 mrna target. 23236518_1 further, several micrornas , specifically mir-1798, mir-1699, mir-223 and mir-1744 were discovered to influence expression of ccnd1, ccne2, cdk1, and cdk3 mrnas, respectively, via their 3'-utr which suggests that post-transcriptional regulation of gene expression influences their expression in laying hens. 23236518_2 moreover, mir-1626 influenced cdkn1a expression and mir-222, mir-1787 and mir-1812 regulated cdkn1b expression via their 3'-utr regions. 26872370_1 these results demonstrate that mir-199a could suppress expression of the luciferase gene by targeting the 3'-utr of hif1a gene 25208211_1 finally we found that il-22 receptor subunit il22ra1 is a direct target of mir-197. 25208211_2 all proving that mir-197 seed sequence at the il22ra1 3'utr is essential for the regulation of il22ra1 by mir-197. 25208211_3 these results, taken together, indicate that il22ra1 and not il-10rb is a direct biochemical target of mir-197. 16616063_2 therefore, mir-15 and mir-16 are natural antisense bcl2 interactors that could be used for therapy of bcl2-overexpressing tumors. 26604796_1 fgfr3 was directly regulated by mir-100 in glioblastoma. 26604796_2 sing a dual-luciferase reporter assay in hek293t cells, we found that wild-type fgfr3 but not mutant fgfr3 was differentially regulated by exogenously introduced mir-100, thus confirming that fgfr3 was directly regulated by mir-100. 26604796_3 another important finding in our work is that fgfr3 is the downstream target of mir-100 in regulating human glioblastoma. 21352471_1 we showed that let-7 directly target socs-1 and caspase-3, whereas mir-181 directly target rassf1a, timp3 as well as nemo-like kinase . 21352471_2 taken together, these findings indicate that socs1 and casp3 are the biologically relevant target of let-7a and let-7b. 21352471_3 fig 9 targeting of socs1 and casp3 3'-utr by let-7, as well as rassf1a, timp3 and nlk by mir-181a. 21352471_4 studies were performed to evaluate and experimentally validate rassf1a, timp-3 and nlk as the bona fide target of translational regulation by mir-181a. 21352471_5 in summary, these data confirm that rassf1a, timp-3 and nlk are the biologically relevant target of mir-181a. 26617698_1 luciferase assays revealed that mir-96 is directly targeted to both binding sites of foxo1 3'-untranslated region and suppressed the foxo1 expression, and subsequently inhibited the expression of bim protein in ptc cells. 26617698_2 moreover, the expression of foxo1 had an inverse correlation with expression of mir-96 in ptc specimens by rt-qpcr and western blot analysis. 26631939_1 analysis of risc-loaded micrornas using a high-throughput platform, as well as functional assays, suggested the p2x7r is a target of microrna-22. 26631939_2 microrna-22 targets the p2x7r in the contralateral hippocampus. 26631939_3 the major finding in the present study was that expression of the p2x7r is regulated post-transcriptionally by mir-22 within the contralateral hippocampus after status epilepticus and this restrains the emergent epilepsy phenotype. 20388705_2 these data establish a direct correlation between a2bar mrna and the mir27b and mir128a mirnas. 20388705_3 these results demonstrate that mir27b and mir128a influence a2bar mrna levels. 20388705_4 these data support the results of the pre-mirna experiments and further demonstrate that mir27b and mir128a regulate a2bar mrna levels. 20388705_5 these data demonstrate that there is an inverse correlation between mir27b and a2bar mrna, supporting evidence for a post-transcriptional mechanism of a2bar regulation by mirna. 25511742_1 furthermore, reg纬was identified as a direct downstream target of mir-7-5p, and there was aninverse correlation between the expression of reggamma and mir-7-5p. 25511742_2 theoverexpression of mir-7-5p inhibited cell proliferation and induced apoptosis by mainly targeting reggamma in vitro and in vivo. 21532615_1 by luciferase assay, we demonstrated fgf-2 and fgfr1 as new direct targets of mir-15 and mir-16 . 21532615_2 mir-15 and mir-16 reconstitution in cancer-associated fibroblasts confirmed fgf-2 and fgfr1 protein reduction, particularly of all the three fgf-2 isoforms . 21532615_3 fgf-2 treatment partially rescued the effect of mir-15/16 cm on du145 cancer cell proliferation . 21532615_4 among mir-15 and mir-16 published targets, ccnd1, wnt3a and bcl-2 genes promote prostate cell proliferation, invasion and survival. 21532615_5 the analysis of wnt3a, ccnd1 and bcl-2 expression by western blotting in tw and mir-15/16 transduced fibroblasts confirmed that the products of these genes are mir-15 and mir-16 targets also in the stromal compartment, underlying the multiple synergic activity of the mirnas on cancer progression . 23893957_3 notably, luciferase activity was significantly lower in cells cotransfected with a luciferase vector containing the crf-r1 3'-utr and a mir-449a vector. 23893957_6 dexamethasone increases mir-449a expression in the anterior pituitary and decreases crf-r1 mrna and crf-r1 protein expressions in the anterior pituitary of rats. 20847741_1 in this study, we show that kshv mir-k3 can regulate viral latency by targeting nuclear factor i/b . 20847741_2 both viral lytic replication and gene expression were inhibited by overexpressing mir-k3 or depleting nfib. 21092188_1 mir-145 downregulated c-myc and the c-myc targetgenes eif4e and cdk4. 21092188_2 these results indicated that downregulation of cdk4 by mir-145 induced a g1 cell-cycle arrest in nsclc cells. 21840484_1 ezh2-regulated micrornas inhibit expression of prc1 proteins bmi1 and ring2. of these, mir-181a, b decreased ring2 protein levels, mir-203 decreased bmi1 protein levels while mir-200b, c decreased both bmi1 and ring2 . 21840484_2 similar to protein levels, real time qpcr showed mir-181a, b and mir-200b, c decreased ring2 transcript levels and mir-200b, c and mir-203 decreased bmi1 transcript levels in bt-549 cells . 21840484_3 the ring2 3'-utr reporters were down-regulated by mir-181a, mir-181b, mir-200b and mir-200c while the bmi1 3'-utr reporters were down-regulated by mir-200b, mir-200c and mir-203 . 21840484_4 taken together, these data suggest that ezh2-mediated epigenetic repression of mir-181a, mir-181b, mir-200b, mir-200c and mir-203 results in an upregulation of prc1 proteins, bmi1 and ring2, and histone code ubiquityl-h2a in advanced prostate cancer. 22513850_1 let-7b is a candidate mir modulating our system because hgma2 is known to be a let-7 target gene . 22513850_2 thus, we suggest that let-7b is part of the molecular circuitry modulating hmga2 and imp2, which in turn modulates lamb2 protein levels. 26234674_2 these findings suggest that mir-214-3p acts as a tumor suppressor and that its downregulation contributes to chemoresistance in esophageal cancer cells by targeting both survivin and cug-bp1. 26234674_3 the stability curves in figure 3d demonstrate enhanced stability of both survivin and cug-bp1 mrna following silencing of mir-214-3p in heso cells. 26234674_4 mir-214-3p negatively regulates survivin and cug-bp1 expression in human esophageal cell lines. 26234674_5 together with our findings, these data regarding targets of mir-214-3p and cug-bp1 in cancer cells raise the intriguing possibility that mir-214-3p and/or cug-bp1 could serve as important regulators of multiple anti-apoptotic effectors in esophageal cancer cells. 25234467_1 the effects of mir-217 overexpression on the proliferation, apoptosis, migration and invasion of spc-a-1 and a549 cells were investigated. 25234467_5 the overexpression of mir-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting kras. 25234467_6 the up-regulation of mir-217 enhanced the sensitivity of spc-a-1 and a549 cells to cisplatin. 25234467_7 in conclusion, mir-217 suppresses tumour development in lung cancer by targeting kras and enhances cell sensitivity to cisplatin. 26224081_1 the results verified a putative binding site between mir-375 and ube3a. 26224081_2 we demonstrated that mir-375 can modulate radiosensitivity of hr-hpv cervical cancer cells by directly downregulating ube3a expression and thereby promoting p53 regulated cell apoptosis. 26224081_3 these results suggest that mir-375 can directly target ube3a and regulate its expression in both hela and siha cells. in both siha and hela cells, we verified the putative binding site between mir-375 and ube3a. 24996183_1 microrna-203 accelerates apoptosis in lps-stimulated alveolar epithelial cells by targeting pik3ca. 24996183_2 mir-203 overexpression also inhibited the protein expression of phosphoinositide 3-kinase catalytic subunit alpha , a direct target of mir-203 identified by bioinformatics, thereby suppressing the pi3k/akt pathway. 24996183_3 underexpression of mir-152 plays a vital role in hepatocarcinogenesis and lack of mir-152 is related to the progression of hcc through deregulation of cell proliferation, motility and apoptosis. 24996183_4 mir-152 may act as a tumor suppressor mirna by also targeting tnfrsf6b and is therefore a potential candidate biomarker for hcc diagnosis, prognosis and molecular therapy. 20890893_2 expression of exemplary in silico identified targets was analyzed in liver samples from ccl4-treated and oil treated balb/c mice , which confirmed upregulation of the potential target genes col1a1, col1a2, col4a5, and col5a3 on ccl4 treatment. 20890893_3 we next transfected mir-29b at different concentrations into immortalized murine hsc. 20890893_6 4c, overexpression of mir-29b resulted in a dose-dependent and significant decrease in expression of col1a1, col4a5, and col5a3, whereas down-regulation of col1a2 failed statistical signifi- cance. 16461460_1 furthermore, mir-20a is down-regulated in breast cancer and, in fact, tgfbr2 protein is expressed in the epithelium of breast cancer . in addition, recently it has been shown that restoration of tgf--beta signaling by introduction of exogenous tgfbr2 in lung cells lacking this protein reduces tumorigenicity in human lung cancers . 16461460_2 interestingly,mir-20a, which we proved to interact with tgfbr2 in vitro, is overexpressed in the lung cancer samples that we analyzed. 26252416_1 robo1 mrna is a direct target of mir- 29a. in addition, the inhibitory effects of mir- 29a upregulation on the viability and proliferation of the mscs were restored by the overexpression of robo1, indicating that mir- 29a inhibited msc viability and proliferation, at least partially, by directly targeting robo1. 26433127_2 these results indicate that mir-200b downregulates ikbkb expression by directly binding to its 3'-utr. 23900351_1 luciferase assays indicated that mir-15a can bind with its putative target site in the 3'-untranslated region of ccne1, suggesting that ccne1 is a direct target of mir-15a. 23900351_2 qpcr and western blot analysis indicated that the overexpression of mir-15a results in the downregulation of ccne1 at the mrna and protein levels 26278569_1 furthermore, luciferase reporter assay and functional analyses indicated that mir-761 directly targeted ing4 and timp2. 26278569_2 luciferase reporter assays and functional analyses further confirmed the role of mir-761 in regulation of nsclc cell metastasis, which is mediated by ing4 and timp2. 26278569_3 together, mir-761 downregulates ing4 and timp2 expression through direct binding to their 3'-utr, and the expressions of mir-761 and ing4 or timp2 mrna reveal inverse correlation in nsclc tissues. 26278569_4 these results suggested that mir-761 plays a role in proliferation and metastasis of nsclc by targeting ing4 and timp2. 22050707_1 mir-20b targets hif1alpha and also modulates vegfalpha expression as reported earlier. 22050707_2 figure 3. regulation of mir-20b and the effect of antagomir-20b on its target vegf and hif-1a expression. 20583868_1 these data suggested that microrna-20a negatively regulated stat3 protein expression at the posttranscriptional level. 20583868_2 taken together, these data suggest that both microrna binding sites on the stat3 3'-utr are functional and that stat3 is one of the direct targets of microrna-20a. 20583868_3 fig. 4. microrna-20a regulates the stat3 expression by binding the 3'-utr of stat3 mrna. 22227207_1 as shown in fig.4a, levels of putative mir-21 targets , including bmpr2, wwp1, satb1, and yod1, were decreased in the lungs of hypoxia-exposed mice, compared with air-exposed control mice. 22227207_2 transfection of mir-21 mimics into pasmcs also leads to a trend of reduced expression of bmpr2, satb1, and yod1 . 22227207_3 as it has been shown previously that reduced expression of bmpr2 contributes to chronic hypoxia-induced ph in mice , our data indicate that mir-21 targets may play a negative role in chronic hypoxia-induced pulmonary vascular remodeling. 18083101_1 increased let-7 paralleled reduced h-ras and hmga2, known let-7 targets. 20393566_2 hotair may also induce prc2 localization to other intergenic regions not present on our tiling arrays. 20393566_3 chip followed by quantitative pcr confirmed that hotair substantially increased prc2 occupancy and h3k27me3 of all targetgenes examined . 21720209_2 the expression pattern detected on the microarray was confirmed for bmp2 but not for fgf9 . in order to find out whether bmp2 is directly or indirectly regulated by mir-140 we used the standard luciferase assay. 21720209_5 these results, together with the mrna array results, confirm bmp2 as a direct target of mir- 140 both in human and chicken primary chondrocytes. 26081516_1 interestingly, all of the used databases predicted icam-1 as target for mir-222. 26081516_2 to further confirm icam-1 as target for mir-222 in emp, mir-222 inhibitor was used to generate empmir-222-down-regulated and corresponding empmock-transfected. treatment of endothelial target cells with the modified emp showed that emp contain functional mir-222 that regulate icam-1 expression in target ecs . 26081516_3 down-regulation of mir-222 in emp abrogated emp-induced inhibition of icam-1 expression after tnf-alpha stimulation. 26081516_4 treatment of apoe?/? mice fed high cholesterol diet with emp mir-222-down-regulated abrogated the emp-promoted inhibition of vascular icam-1 expression . 25183046_1 the binding of mir-93 on rbl2 3'-utr was determined by double luciferase system. 25183046_2 furthermore, we found that mir-93 directly targeted rbl2 by binding to its 3'-utr in renal cancer cells. 25183046_3 together, these results demonstrated that mir-93 could regulate the expression of rbl2 in renal cancer cells by directly binding to its 3'-utr. 26755652_1 moreover, we demonstrated that gli3 was a direct target of mir-133b and the expression of cyclin b1 and cyclin d1 was enhanced by mir-133b mimics but decreased by its inhibitors. 26755652_2 taken together, these data imply that gli3 is a direct target of mir-133b in human sertoli cells. 21638050_1 initially, the ability of mir-28 to regulate the 3' untranslated region of nrf2 mrna was evaluated via luciferase reporter assay. 21638050_2 collectively, these data indicate an inverse correlation between nrf2 expression and mir-28 levels in mammary epithelial cells. 21638050_3 we examined nrf2 expression with qrt-pcr and western blotting in mcf-7 cells and found pre-mir-28 transfection resulted in a 35% decrease in nrf2 mrna levels and a more than 90% decrease in nrf2 protein levels . 21638050_4 these results confirm that mir-28 negatively regulates nrf2 expression by targeting the 3- utr of nrf2 mrna. 21638050_5 collectively, these data demonstrate that nrf2 is subject to regulation by mir-28 through alterations of mrna and protein stability. 21638050_6 these results demonstrate that mir-28 mediated changes in nrf2 protein stability were not due to the regulation of keap1 expression level or altered keap1/nrf2 interaction. 25487955_3 moreover, over-expression of mir-449a inhibited the expression of podoplanin by down-regulating maz which could positively control the promoter activities via binding to the promoter of pdpn, demonstrated by luciferase assays and chromatin immunoprecipitation assays. 25487955_4 further, the pi3k/akt pathway was blocked when maz was down-regulated by mir-449a. 17542919_1 the first 51 nucleotides of the 5'-utr of shia mrna can clearly interact with the rbs and the first codon of the orf. the srna ryhb increases shia mrna stability. 17542919_2 ryhb directly pairs at the 5'-untranslated region of the shia mrna to disrupt an intrinsic inhibitory structure that sequesters the ribosome-binding site and the first translation codon. 26187928_1 the 3'-utrs of tnfaip1 and smad4 mrnas contained sequences complementary to the mir-224 seed sequence. 26187928_2 to verify whether tnfaip1 and smad4 are direct targets of mir-224, we cotransfected each of the 3'-utrs and mir-224 mimics in 293t cells. 26187928_4 overexpression of mir-224 markedly reduced mrna and protein expressions of tnfaip1 and smad4, respectively, in h1299, h1573, and h460 cells . 26187928_5 conversely, knockdown of mir-224 increased expression of tnfaip1 and smad4 mrna and protein levels, respectively, in a549 cells. 22915806_1 kshv mir-k10 variants inhibit tgf-beta signaling by targeting tgf-beta type ii receptor . 22915806_3 these results indicate that mir-k10 variants manipulate the tgf-beta pathway to confer cells with resistance to the growth-inhibitory effect of tgf-beta. 25728840_2 we also found that sp1 transcriptionally up-regulates hsa-mir-320a expression. 26708607_1 moreover, rapamycin, an autophagy promoter was able to partly reverse the effect of mir-30a and luciferase reporter assay identified that mir-30a directly binds to the 3'-utr of beclin-1 gene, which further confirmed that mir-30a reduced chemoresistance via suppressing beclin-1-mediated autophagy. 23113351_1 mirna-29 members induced apoptosis through p53 gene activation, the effect of mirna-29a on osteoblastic cells was independent on p53 expression level. 23113351_2 moreover, bcl-2 and mcl-1 were earlier demonstrated to be the direct targets of mirna-29 in many types of cancer tissues and cancers. in addition, enhanced expression of mirna-29a increased the expression of two tumor suppressor genes, e2f1 and e2f3. 22984081_1 we formally tested the ability of the viral mirna to decrease the expression of the nlrp3 3'-utr luciferase construct and observed that only ebv mir-bart15 targeted this construct.transfection 22984081_2 of ebv mir-bart15 into pma-treated thp-1 cells reduced endogenous nlrp3 protein levels. 26820102_1 in addition, we found that mir-655 was negatively correlated with prrx1 in cell lines and clinical samples. 26820102_2 overexpression of mir-655 significantly suppressed prrx1, as demonstrated by prrx1 3'-untranslated region luciferase report assay. 26820102_3 figure 6. oncogene prrx1 was specifically targeted by mir-655. 25634129_2 the present study aimed to investigate whether mir-218 regulated the expression of adipor2 using immunoblotting, reverse transcription quantitative polymerase chain reaction and luciferase assays. 25634129_3 the protein level and the mrna level of adipor2 were reduced when mir- 218 was expressed in hepg2 cells. 25634129_4 additionally, overexpression of mir- 218 repressed the activity of a luciferase reporter containing the 3'utr of adipor2. 25634129_5 these results suggested that mir-218 directly binds to the 3'utr of adipor2 mrna and reduces adipor2 expression. 21882343_1 furthermore, our in vivo and in vitro studies showed that mir-21 regulates pdcd4 in sle t lymphocytes. 21882343_2 pdcd4 is directly targeted by mir-21 and regulates pathways involved in apoptosis, cell cycle and differentiation . 21882343_3 we found that mir-21 expression in lupus b and t cells is up-regulated and that in vivo silencing of mir-21 using a tiny seed-targeting lna reversed splenomegaly, one of the cardinal manifestations of autoimmunity in b6.sle123 mice, and de-repressed pdcd4 expression in vivo and in vitro. 26681446_1 we conclude that mir-9, mir-96, mir-133, and mir-146a interact directly with their binding sites in the gdnf 3'-utr; moreover, mir-9, mir-96, and mir-146a regulate the expression of gdnf in vitro. 26423933_1 and we observed that nrn1 with the function of synapse plasticity was a potential target of mir-574-5p. 26423933_2 mir-574-5p can specifically reduce the expression of nrn1 protein 24606471_1 further analysis revealed that over-expression of mir-130a increased cell apoptosis and inhibited proliferation of nsclc cells treated with gefitinib, whereas lowering the expression of mir-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant nsclc cell lines, suggesting that mir-130a overcomes gefitinib resistance. 24606471_2 we also demonstrated that mir-130a binds to the 3'-utr of met and significantly suppresses its expression 26722432_2 taken together, these results indicated that mir-592 regulates endogenous dek expression through mrna translational repression. 26268657_1 the transcription factor c-myb is expressed preferentially by immature nk cells, is a direct target of mir-15/16, and is increased in 15a/16-1 floxed knockout nk cells. 26268657_3 further, the myb 3' utr was biochemically confirmed asa target of mir-15/16,and myb mrna and protein were differentially expressed between mir-15/16-deficient and sufficient immature nk cells in vivo. 26268657_4 thus, murine myb is a direct target of mir-15/16 family mirnas, consistent with the increased mrna and protein expression in 15a/16-1fkonk cells. 26268657_5 myb was confirmed as a direct target of mir-15/16 in vitro using both gain- and loss-of-function approaches. 17919492_4 down-regulation of mir-122 and up-regulation of ho-1 may be new strategies for anti-hcv intervention and cytoprotection. 25890085_1 ezh2-regulated mir-30a targeted kpnb1 in mpnst cells. 25890085_2 this result suggested that mir-30a directly suppresses kpnb1 by targeting the kpnb1 mrna 3'-utr region. 25436011_1 mir-27a directly targets the kras gene by interaction with the 3'-utr. 25436011_2 these data indicated that mir-27a directly targets kras in escc by binding to the 3'-utr of the kras gene. 26487685_1 this result shows that dlk1 may be targeted by mir-329. 26487685_2 because dlk1 mrna level was not altered in the ko mice, mir-329 appears to regulate dlk1 expression in a translational inhibition rather than an mrna stabilization manner . 26487685_3 fig. 5. mir-329 targets the dlk1 gene by interacting with the dlk1 3'-utr. 23936094_1 we demonstrate that the transcriptional factor gli1 was a target of mir-202-3p and plays an essential role as a mediator of the biological effects of mir-202-3p in gastric cancer. 23936094_2 these results support the premise that downregulation of mir-202-3p increases the level of gli1 gene in gastric cancer. 23936094_3 this result strongly indicates that 3'-utr of gli1 carries the direct binding sites of mir-202-3p. 22630347_1 the results indicate that reck is a direct mir-21 target . 22630347_2 these data indicated that mir-21 had a significant impact ontumor growth and invasion via regulation of reck. 22630347_3 further, we have demonstrated in vitro and in vivo, using gbmcells and ln229 glioma xenografts in nude mice, that the entirepathway regulates glioma cell prolifer-ation and invasion by directly controlling the mir-21 target, reck . 26717922_1 these findings suggested that mir-223-3p targets fam5c and downregulates fam5c 23999873_2 up-regulation of mir-429 inhibits invasion and promotes apoptosis in ec cells by targeting bcl-2 and sp1. 23999873_3 our findings suggest that bcl-2 and sp1 may serve as major targets of mir-429. 21552422_1 p27, a key inhibitor of cell cycle, was verified as the target of mir-148a, indicating mir-148a might downregulate p27 expression to promote gastric cell proliferation. 21552422_2 moreover, p27, a key inhibitor of cell cycle, was identified as the direct target of mir-148a, suggesting that mir-148a might exert its function through the downregulation of p27. 21552422_3 furthermore, the inverse correlation was observed between mir-148a and p27 in tumor samples , suggesting that mir-148a could negatively regulate p27 expression in human gastric cancer. 22894925_1 in this study, it was shown that rsv infection of a human alveolar epithelial cell line induced five mirnas and repressed two mirnas , and showed that rsv g protein triggered let-7f expression. 26084306_1 in silico analyses and studies in cancer demonstrated that microrna mir-223 targets parp-1. 25631713_2 to further clarify whether mmp-2/9 in cells overexpressing mir-130a is upregulated by decreasing cav-1, we treated cells with cavtratin, a cav-1 scaffolding domain peptide. 25631713_3 figure 5d indicates that cavtratin could decrease mir-130a-induced overexpression of mmp-2 and mmp-9 in bmecs. 19133256_1 this is also supported by the analysis of cox-2 protein/mrna ratio , demonstrating that mir-101 directly and specifically interacts with cox-2 mrna and promotes cox-2 protein silencing mostly through a translational repression mechanism. 19133256_2 these data support the association between cox-2 overexpression and colorectal cancer malignancy and suggest an important role for mir-101 in cox-2 regulation in tumoral tissues and metastases. 20102618_1 the mrna 3'utr of candidate mir-9 targetgene nf-κb1 carries a putative mir-9 binding site .4a. as a result, pri-mir-9 had no effect on the intensity of egfp fluorescence in this 3'utr mutant vector , highlighting the importance of this mir-9 binding site. 20102618_3 these data suggested that mir-9 negatively regulate the expression of nf-κb1 through mrna cleavage mechanism. 26164195_1 recent studies have documented that nrf2 was repressed by mir-144 in k562 cells and cerebromicrovascular endothelial cells . 26164195_2 to validate whether mir-144 directly recognized the 3'-utr of nrf2, we generated serial constructs harboring the 3'-utr segment of nrf2 and its mutant fused downstream to the luciferase coding sequence. 26164195_3 protein levels of nrf2 was further reduced when transfected with mir-144 mimic and enhanced when transfected with mir-144 inhibitor . 26164195_4 when exposed to ng,transfection with mir-144 mimic or inhibitor had no significant effect on nrf2 protein expression. 21998710_1 we showed that mir-29a could repress p42.3 expression at both the mrna and protein levels via directly binding to its 3'utr. in addition, there was no significant decline of the fluorescent intensity in the group that was co-transfected with mutpcdna3/egfp/p42.3 21998710_2 , further confirming that mir-29a induced the downregulation of p42.3 gene expression via the specific binding of the putative site of the p42.3- 3'-utr. 21998710_3 this suggested that mir-29a could regulate the expression of the p42.3 gene in mkn-45 cells. 21998710_4 this indicated that mir-29a could inhibit cell proliferation via repressing the expression of p42.3. 22314666_2 mir-141 could target 3'-untranslated region of shp mrna resulting in translational suppression and rna degradation. 22314666_3 taken together, these data suggest that shp is a targetfor mir-141 and is downregulated in pca cells with the involvement of upregulation of mir-141. in addition, mir-141 may suppress shp expression through translational suppression and rna degradation. 22314666_4 fig. 3. mir-141 target shp 3'-utr resulting in translational suppression. 22314666_5 interestingly, treatment of cells with anti-mir-141 also decreased dht induced psa luciferase activity , suggesting that shp and mir-141 mediate dht-induced ar transcriptional activity in lncap cells. 22101765_1 finally, we found that the 3' untranslated region of mapk14 was directly targeted by mir-141 or mir-200a, and we identified the genuine binding site of these mirnas in humans and mice . 22101765_2 mir-141 and mir-200a inhibit p38alpha. 22101765_3 indeed, expression of mitogen-activated protein kinase 14 was significantly downregulated by mir-141 or mir-200a overexpression, as evaluated by microarrays and confirmed by quantitative rt-pcr . 22101765_4 the expression of mapk14 was unchanged by overexpression of mir-200c or mir-200b , suggesting that only mir-141 and mir-200a are involved in the regulation of the mapk pathway. 22101765_6 these data show that mir-141 and mir-200a are key direct regulators of p38alpha. 23578572_2 thus, mir-24 which functions as a tumor suppressor gene through down-regulating lpaat-beta, may be a promising gene therapeutic target against osteosarcoma proliferation. 23578572_3 taken together, these in vivo results strongly suggest that mir-24 may play an important role in inhibiting osteosarcoma growth through suppression of lpaat-beta. 22402365_1 nutrition restriction induced an increase in the level of the mir-140-3p target, nad+-dependent sirt1. 22402365_2 furthermore, this study demonstrates that there is a direct link between mir-140-3p, a chondrocytes-specific mirna, and sirt1 in the egp. 26376347_1 all together, these results suggest that atf2 is a direct target of mir-26a and can be regulated by mir-26a in microglia during pathogen-associated molecular pattern stimulation. 26376347_2 collectively, these results suggest that mir-26a regulates the production of il-6 by targeting of atf2. in addition, we have identified that mir-26a can modulate the production of il-6 by directly targeting atf2 post-transcriptionally in microglial cells. 26503628_1 in western blotting and luciferase assay, nlk was identified as a direct and functional target of mir-92b. 26503628_2 collectively, our results indicated that nlk is a direct target of mir-92b. 26503628_3 moreover, nlk as a direct target of mir-92b was involved in the mir-92b-induced cell proliferation. 17827156_1 mir145 down-regulates a reporter gene with sequences from the 3-utr of irs-1. 17827156_2 mir145 also down-regulates the igf-ir , although to a lesser extent than irs-1. 17827156_3 irs-2 expression is not decreased , as expected from the data base, indicating that irs-2 is not targeted by mir145. in this communication, we have focused on mir145 and its targeting of irs-1. 17827156_4 the results of repeated experiments are summarized in fig. 5. as expected, sirna markedly decreases irs-1 levels, but these remain constant in cells transfected with mir145 synthetic oligos. in fact, there was a small increase of irs-1 mrna in cells transfected with the mir oligo. 17827156_6 these experiments show that mir145 down-regulates the irs-1 protein, but not the mrna. 26079799_1 additionally, the 3- -untranslated region of cd44 mrna was the direct target of microrna-199a-3p . in the current study, we evaluated the role of cd44 in osteosarcoma progression and also identified that mir-199a-3p could modulate the drug sensitivity of osteosarcoma through targeting cd44. 26079799_2 these results suggested that mir-199a-3p repressed cd44 expression in both a dose-dependent and time-dependent manner. 26079799_3 we demonstrated that cd44 is a direct target of mir-199a-3p in osteosarcoma. 26617712_1 we also identified -beta-catenin as a target gene of mir-214 and demonstrated its association with treg cell differentiation. 26617712_2 our results showed that mir-214 directly down-regulates the expression of -beta-catenin by targeting the 3'-utr and further suppresses the generation of treg cells. in our study, we found that mir-214 inhibited the luciferase activity of a reporter containing the wild-type -beta-catenin 3'-utr but not that of a mutated 3'-utr , indicating that mir-214 targets -beta-catenin. the novel finding of this study is that mir-214 regulates functional -beta-catenin to influence dcs and thus balance immunity and tolerance. 26809508_1 spry2 has been shown to be a direct target of microrna-21 in other cellular systems. 26809508_2 we overexpressed mir-21 in mec-1 cells to study whether it can regulate spry2 in cll-cells. 26809508_3 notably, we observed a decrease in spry2 expression in mec-1 cells expressing high levels of mir-21 compared to those with an empty-vector control. in summary, our results here demonstrate that spry2 is deregulated by mir-21 in cll-cells. 26809508_4 the results here also, provide a mechanism by which mir-21 promotes cll progression via down-regulation of spry2. 26165754_1 mir-20a-5p which potentially targets atg16l1 by prediction was selected for further investigation. 26165754_3 these results confirmed the inhibitory binding of mir-20a-5p to the 3'-utr of atg16l1 mrna. 26165754_4 these results suggest that mir-20a-5p could negatively regulate autophagy through suppressing atg16l1 by binding to its 3'-utr in hk-2 cells under hypoxic conditions. 17135249_1 this anti-apoptotic role of mir-20a may explain some of the oncogenic capacities of the mir-17-92 cluster. 23593282_1 vegfc protein levels were also decreased in cells and culture medium upon transfection with an mir-27b mimic, while vegfc levels they increased upon transfection of an anti-mir-27b mimic . in vivo, vegfc protein levels were lower in mir-27b xenografts compared to in the nc group . 23593282_3 although there are a set of predicted mir-27b targets, vegfc as a functional downstream target of mir-27b can be fully confirmed in our experiments. 25330011_2 and mir-375 over-expression directly inhibited ecadherin expression and facilitated paclitaxel-resistance. 25330011_3 thus, our findings indicate that mir-375 over-expression promotes paclitaxel-induced emt partly by directly targeting ecadherin in cervical cancer cells. 25330011_4 here, we observed that ecadherin is a direct target of mir-375 in cervical cancer cells; moreover, re-expression of ecadherin partly reversed the emt phenotype and paclitaxel -resistance induced by mir-375 in cervical cancer cells. 25750939_1 mirna target prediction software was used, and vhl was found to be one of the target genes of mir-331-3p. 25750939_2 all of these results show that hbv up-regulated mir-331-3p expression in hcc cell lines and mir-331-3p could inhibit vhl expression by directly targeting its 3'-utr. 25750939_3 here, we detected the expressions of mir-331-3p in different hcc cell lines and confirmed vhl was the target gene of mir-331-3p. 25750939_4 therefore, we concluded that vhl expression could be inhibited by mir-331-3p in hcc cell lines. 25750939_5 these data suggested that mir- 331-3p inhibited vhl expression by directly targeting its 3'-utr. 22992343_1 mir-146a expression is up-regulated in a majority of gastric cancers where it targets card10 and cops8, inhibiting gpcr-mediated activation of nf-kappab, thus reducing expression of nf-kappab-regulated tumor-promoting cytokines and growth factors. 22992343_2 by targeting components of several nf-kappab-activating pathways, mir-146a is a key component in the regulation of nf-kappab activity. 22992343_3 in summary, we confirmed earlier observations showing that mir-146a directly targets irak1 and we furthermore identified two new targets, card10 and cops8, which codes for proteins suggested to be involved in nf-kappab activation. 18949056_2 they demonstrate that levels of the mirna mir15a are decreased in livers of patients with autosomal recessive and autosomal dominant polycystic kidney disease and congenital hepatic fibrosis as well as in the pkc rat model of arpkd. 26542803_1 all three programs identified the chromatin remodeling complex factor smarcd1 as a mir-7 target . 26542803_4 the result demonstrated that mir-7 overexpression reduced smarcd1 expression in all three cell lines. 26542803_5 we next examined whether mir-7 targeted the 3'-utr of smarcd1 to inhibit its expression. 26542803_6 the results showed that mir-7 expression downregulated the luciferase activity of the reporter plasmid containing the 3'-utr of smarcd1 but did not affect the pgl3-control vector . 26542803_7 these results suggested that mir-7 downregulated smarcd1 by targeting its 3'-utr. 25468475_2 moreover, mir-125b regulated erbb2 mrna and protein expression and regulated angiogenesis association with regulating the expression of vegf in heat-denatured huvecs. 25468475_4 2e and f, an inverse correlation was observed between vegf protein levels and mir-125b expression , suggesting that the expression of mir 125b may regulates vegf during the recovery of heat denatured dermis and heat-denatured huvecs. 25468475_5 collectively, these results suggest that erbb2 may be a mediator between mir-125b and vegf during the recovery of heat denatured dermis and heat-denatured huvecs. 26282993_1 indicating that nurr1 is a direct target of mir-132. 26282993_2 knockdown of mir-132 using mir-132 inhibitors led to increased nurr1 protein expression in mgcs . 22496917_2 introduction of anti-mir-148a increased pten protein and mrna expression, suggesting that pten was targeted by mir-148a. 22771761_1 we also examined the protein level of a known mir-184 target, akt2 . 22766504_2 mir-145 target a putative binding site in the 3'utr of pak4. in this study, we investigated the levels of mir-145 in human colon cancer cells using qrt-pcr and found markedly decreased levels compared to normal epithelial cells. 22766504_3 we identified pak4 as a novel target of mir-145 using informatics screening. 22766504_4 additionally, we demonstrated that mir-145 target a putative binding site in the 3'-utr of pak4 and that its abundance is inversely associated with mir-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. 22766504_5 taken together, these findings demonstrate that mir-145 downregulates p-erk expression by targeting pak4 and leads to inhibition of tumor growth. 22081998_1 based on these observations, bdnf represents a novel target through which mir-206 controls the initiation and maintenance of the differentiated state of muscle cells. 22081998_2 mir-206 sites are present in the bdnf 3'-utr. 22081998_3 together these experiments demonstrate that mir-206 specifically represses bdnf through target sites present in the long 3'-utr transcript. 18082412_1 increased levels of nuclear rest in hd leads to both a direct repression of rest target genes such as bdnf and to an indirect activation of gene expression by increased repression of mirnaexpression the latter is exemplified by loss of mir-132, in turn leading to higher levels of p250gap mrna. 26471303_1 we also observed that mir-34a bound directly to the 3- -untranslated region of fkbp1b. 26471303_2 these results suggest that mir-34a regulates adipogenesis by targeting fkbp1b expression. 26471303_3 these results suggest that mir-34a directly binds to and negatively regulates fkbp1b. in summary, mir-34a inhibits adipogenesis by direct targeting fkbp1b which is a negative regulator of adipogenesis. 26692944_1 moreover, igf2bp1 was a direct target of mir-506 in glioblastoma cells. 26692944_2 knockdown of igf2bp1 recapitulated the anti-proliferative and anti-invasive effects of mir-506, whereas igf2bp1 overexpression antagonized the tumor-suppressive function of mir-506. 26617808_1 our study suggested that mir-338-3p is significantly decreased in gastric cancer, and inhibits cell proliferation, migration and invasion partially via the downregulation of adam17. 26617808_2 furthermore, we identified adam17 as a direct target of mir-338-3p, and adam17 overexpression partially attenuated the tumor suppressive effect of mir-338-3p in gastric cancer cells. 26617808_3 these results indicated that adam17 was a direct target of mir-338-3p in gastric cancer cells. in the present study, we identified that adam17 was a direct target of mir-338-3p in gastric cancer cells, and supplement of adam17 remarkably attenuated the tumor suppressive effects of mir-338-3p on gastric cancer cells. 21983159_1 these data demonstrate that mir-181 levels change in response to stroke and inversely correlate with levels of grp78. 21983159_4 thus grp78 is a major target of mir-181a in determining cell survival or death from stress. 21983159_5 fig. 1 hspa5 is the target of mir-181. 23272142_1 lpar1, etar and rhoa are new target of mir-200c. 23272142_2 the interaction among the 3'-utrs of etar, lpar1 and rhoa with mir-200c was analyzed using the psicheck2 luciferase assay system. 23272142_3 mir-200c mimic significantly reduced luciferase expression in cells co-transfected with the 3'-utr of etar, lpar1 and rhoa compared to mimic control the decrease in luciferase activity was prevented when the 3'-utr complementary sequences were used . 23272142_4 down-regulation of etar, lpar1 and rhoa proteins by mir-200c was confirmed by western blot in htm cells . 23272142_5 here, we showed that mir-200c is a direct postranscriptional inhibitor of genes relevant to the physiologic regulation of tm cell contraction including the validated target zinc finger e-box binding homeobox 1 and 2 , and formin homology 2 domain containing 1 , as well as three novel target: lysophosphatidic acid receptor 1 , endothelin a receptor , and rhoa kinase . 26863629_1 figure 1: mir-217 expression level is inversely correlated with cage. 26863629_2 taken together, these results suggest that mir-217 targets cage. 26863629_3 taken together, these results indicate that mir-217 negatively regulates the expression of cage. 26863629_4 our results show that mir-217-cage feedback loop serves as a target for overcoming resistance to various anti-cancer drugs, including egfr and her2 inhibitors. 20486779_1 luciferase reporter assays demonstrated that mir-138 directly targeted the 3' untranslated region of eid-1, implying that the negative role of mir-138 in the adipocyte differentiation of had-mscs is at least partially mediated via repressing eid-1. 20486779_2 these data indicated that the translation of eid-1 protein might be regulated by mir-138. 20486779_3 taken together, these results reveal that mir-138 can regulate eid-1 protein expression through a partially complementary binding site in the 3'-utr of eid-1, leading to decreased adipogenesis of had-mscs. 26898246_1 eif2alpha is confirmed as the congenerous target of mir-30b-5p and mir-30c-5p, essential to the anti-apoptotic function of these mirs. in conclusion, we unravels a new mirs-based mechanism that helps maintain intracellular proteostasis and promote cell survival during er stress through upregulation of mir-30b-5p and mir-30c-5p which target eif2alpha and thereby inhibit the p-eif2alpha/atf4/chop pro-apoptotic pathway, identifying mir-30b-5p and mir-30c-5p as potentially new targets for anti-cancer therapies. 26898246_2 our further investigation demonstrates that mir-30b-5p and mir-30c-5p, which are upregulated after eif2alpha phosphorylation has increased, target eif2alpha , lead to suppression of the p-eif2alpha -atf4-chop pro-apoptotic pathway, and thereby promote cell proliferation and confer resistance to apoptosis in the cancer cells both under basal culture condition and during proteasome inhibition, unraveling a new mirs-based mechanism for suppressing general protein synthesis and improving cell survival in the upr. 26898246_3 these results confirm that mir-30b-5p and mir-30c-5p can specifically target eif2a in both hepg2 and mda-mb-453 cells. 24771295_1 the down-regulated mirna-30a could attenuate 1 h ogd/24 h reoxygenation-induced ischemic injury in n2a cells and cultured cortical neurons through enhancing beclin 1-mediated autophagy, as mirna-30a recognized the 3'-untranslated region of beclin 1 mrna to negatively regulate beclin 1-protein level via promoting beclin 1 messenger rna degradation, and beclin 1 sirna abolished anti-mir-30a-induced neuroprotection in 1 h ogd/24 h reoxygenation treated n2a cells. 23166348_1 in the absence of mir-133a, ip3rii protein levels were increased while ip3rii mrna expression was diminished . 23166348_2 together, these data confirm that mir-133a regulates ip3rii post-transcriptionally. together, these results imply that lack of mir-133a-mediated repression during hypertrophy augments ip3rii protein expression. 23166348_3 these data indicate that increasing mir-133a down-regulates ip3rii. 26334393_1 as shown in figure 2a-2b, the expression of mir-200b was substantially decreased in 6/7 escc cell lines as compared to an immortalized esophageal cell line , and a low expression of mir-200b was associated with a high expression of zeb1/2 mrna in this panel of escc cell lines .we 21252292_1 nf-yb is a direct targetfor mir-485-3p. it is noteworthy that the decreased expression of mir-485-3p in cem/vm-1-5 cells is inversely related to the overexpression of nf-yb protein . 21252292_3 taken together, mir-485-3p-mediated down-regulation of nf-yb in cem/vm-1-5 cells was accompanied by increased sensitivity of cem/vm-1-5 cells to top2 inhibitors. 22012839_1 pdgfralpha was the target of microrna-140 in mpmc. 22012839_2 this result indicates mir-140 directly binds 3' utr of pdgfra. 22012839_3 third, to further explore the effect of mir-140 on the pdgfra protein level, mpmcs were transfected with mir-140 mimics or inhibitors, and western blot was carried out. 22012839_4 compared with scrambled mirna, mir-140 mimics decreased pdgfra expression, whereas mir-140 inhibitors slightly increased pdgfra expression . 22012839_5 these results indicated mir-140 can inhibit pdgfra expression by directly targeting 3' utr of pdgfra. 20667897_1 pkm2 is a direct target of the tumor-suppressive mir-326. 20667897_2 pkm2 is a direct and functional target of mir-326 suggesting that mir-326 could regulate the glioma metabolism through its regulation. 20667897_3 mutations in 3 bases each in the -渟eed" complementary sites for mir-326 completely rescued the repression of pkm2 3'-utr-luciferase activity . 20667897_4 these data indicated that pkm2 is a direct and functional target of mir-326. 20667897_5 these data suggest mir-326 as a possible endogenous regulator of pkm2 expression. 21383697_1 among the candidates, the 3'-untranslated regions of mtor and fgfr3 contained regions that matched the seed sequences of mir-99a . 21383697_2 a luciferase reporter assay in c-src-transformed cells showed that mir-99a specifically targeted the mir-99a binding sequences in mtor and fgfr3 mrnas . 21383697_3 these results indicate that mir-99a can directly target mtor and fgfr3 mrna to regulate their expression. 21383697_4 these findings show that mir-99a can target endogenous mtor/fgfr3, and suggest that downregulation of mir-99a by c-src activation is tightly associated with the upregulation of mtor/fgfr3 in c-src-transformed cells. 25543482_2 moreover, knockdown of mir-21 increased the expressions of pdcd4 and pten at the protein level but not at the mrna level. 26440052_1 by overexpressing or inhibiting mir-137 in cancer cells, we experimentally confirmed that mir-137 directly recognized the 3'-utr of the rasgrf1 transcript and regulated rasgrf1 expression. 26440052_2 these results revealed that mir-137 directly regulates rasgrf1 by binding to the 3'-utr region of rasgrf1. 26440052_3 at this concentration, it is obvious that mir-137 can efficiently suppress rasgrf1 expression in astrocytoma cells. 26440052_4 the ectopic expression of rasgrf1 significantly reversed the suppression of the proliferation and apoptosis induced by mir-137 in vitro in u251 cells, indicating that mir-137 suppressed rasgrf1 expression by binding directly to the 3'-utr of rasgrf1 in astrocytomas. 21778430_1 using global gene profiling and argonaute-2 immunoprecipitation approaches, we showed that mir-195 regulates the expression of a number of cell cycle genes, including checkpoint kinase 1 , which we identified as a highly conserved direct target of mir-195. 21778430_3 a plasmid consisting of the chek1 3'-utr linked to a constitutively active luciferase reporter was transfected into cos cells along with increasing amounts of mir-195 mimic. 21778430_4 the chek1 3'-utr luciferase reporter displayed a dose-dependent repression in activity by mir-195 . 21778430_5 mutation of the mir-195 targetsite abolished repression by mir-195, which demonstrates that this effect was dependent on binding of mir-195 to its targetsite within the 3'-utr of chek1 . 26500110_1 smad7 and zeb1 were potential targets of mir-21 and mir-200b, respectively. 26766590_1 consistent with its mrna expression protein,the protein level of kdm1b was found to be decreased under hypoxia or increased when mir-215 was suppressed in those cells. 26766590_2 the luciferase expression was repressed by mir-215 in a dose-dependent manner in hek293t cells, whereas expression of the luciferase with mutated 30 utr was not altered significantly . in sum, these data support the notion that kdm1bserves as a direct target of mir-215. 26766590_3 together, these data indicate that mir-215 functions to positively control the biological properties of gics under hypoxia mainly through suppressing its target kdm1b. 19780716_1 a targetsequence for mirna mir-346 was found in the 5'utr of rip140 mrna; this mirna is also expressed endogenously in mousebrain and p19 cells. 19780716_2 real-time rt-pcr of rip140 showed that rip140 mrna levels were not affected in p19 cells transfected with either a mir-346 mimic or a mir-346 inhibitor , indicating that mir-346 did not affect transcription or mrna stability of rip140. 19780716_3 these results supported that mir-346 up-regulated rip140 expression at the translational level. 19780716_4 however, mir-346 inhibitor was no longer effective in further enhancing at-ra-induced reporter activity in rip140-knockdown cells, thus confirming that regulation of protein expression by the mir-346 occurs specifically via its interaction with rip140. 21292542_1 furthermore, overexpression of let-7a decreased the expression of its targets nanog, oct4, klf4, and bmi1 . 26138755_1 of the predicted targets of mir-9a, we find that loss of mir-9a enhances the level of snpfr1. 26138755_2 we show via an in vitro binding assay that mir-9a binds to snpfr1 mrna in insect cells and to the mammalian orthologue npy2r in rat insulinoma cells. 26138755_3 this confirms that mir-9a binds to the 3'-utrs of snpfr1 and npy2r. 26138755_4 these results support the hypothesis that the snpfr1 and npy2r mrnas are legitimate targets of mir-9a/mir-9. 26138755_5 these results confirm that mir-9a in ipcs regulates insulin signalling and body growth via its target snpfr1 . 26183850_1 suppressor of cytokine signaling 6 was identified as a direct target of mir-142-3p, and mir-142-3p down-regulated the expression of socs6 by directly binding to its 3'- utr . 26183850_2 knockdown of socs6 abrogated the effects of mir-142-3p down-regulation. 26183850_3 these results indicate that mir-142-3p binds directly to the socs6 3'-utr to repress its gene expression. 26183850_4 collectively, these data indicate that mir-142-3p inhibits cell growth by suppressing its target gene socs6. 26250586_1 luciferase assay using the eif4e 3 ' -utr reporter carrying a putative mir-34c-3p target sequence revealed eif4e to be a specific target of mir-34c-3p. 26250586_2 overexpression of mir-34c-3p in nscls cell lines led to significant reduction in mrna and protein levels of eif4e, whereas inhibition of mir-34c-3p resulted in significant increase in eif4e protein levels, confirming eif4e to be a direct target of mir-34c-3p in nscls. 26250586_3 here, we show that mir-34c-3p directly targets eif4e expression and represses nsclc cell proliferation, migration and invasion. 24484937_2 importantly, over-expression of mir181b in metastatic breast cancer cells inhibits metastasis formation in vivo in immunodeficient mice. 24484937_3 finally, we demonstrated that curcumin up-regulates mir181b and down-regulates cxcl1 and -2 in cells isolated from several primary human breast cancers. 21044961_1 mir-210 target fgfrl1 3'-utr directly. 21044961_2 these results suggest that fgfrl1 is a direct and robust targetgene of mir-210 in escc. 21044961_3 these results suggested that these five sites in the fgfrl1 3'-utr are targetsites of mir-210. 21044961_4 the treatment by 2- -o-methylated antisense rna of mir-210 significantly enhanced the expression levels of fgfrl1 mrna and protein . 21044961_5 these results may indicate that mir-210 endogenously regulates the expression levels of fgfrl1 and cancer cell proliferation. 25433493_1 consistent with the reporter assay, we observed an evident decrease of fscn1 protein in presence of mir-133b mimics compared to scramble control in both of hgc-27 and mgc-803 cells. 25433493_2 meanwhile, we also noticed that the expression level of fscn1 in hgc-27 and mgc-803 cells was higher than that in ges cells which was consistent with low expression of mir-133b in gc cells . 25433493_3 these results indicated that fscn1 might play important roles in gc as an oncogene and mir-133b regulated gc cell proliferation, migration and invasion through targeting fscn1. 26451302_1 we found that expression of a luciferase reporter containing 3' utr of stat3 was inhibited by cotransfection with mir-197 mimics, whereas reporter plasmid without 30 utr of stat3 showed no change in luciferase activity . 26451302_2 these results suggested that il- 6 stimulation could downregulate expression of mir-197, and downregulation of mir-197 in turn upregulated protein level of stat3 in hcc cells. 26451302_3 figure 2. mir-197 is downregulated by il-6 and targets stat3 in hcc cells. 26545583_1 mir-363 targets the myo1b 3- utr and reduces myo1b expression. of these, myo1b was tested in our studies since its 3- utr contains two potential mir-363 binding sites. 22796494_2 2c and e, the results indicate that the overexpression of mir-145 decreased both the mrna and protein levels of ccnd2 in mgcs. 22796494_3 furthermore, the mir-145 inhibitor enhanced the mrna and protein expressions of ccnd2 . 21792910_1 luciferase reporter assay revealed the direct interaction of mir-195 with the cyclin e1 3'utr. 21792910_2 these results showed that mir-195 down-regulates endogenous cyclin e1 expression and upregulates p21 expression, resulting in the attenuation of cell cycle progression and cell proliferation. 21792910_3 these results suggested a direct interaction between mir-195 and cyclin e1 3' utr in lx-2 cells.fig. 5. interaction ofmir-195 withthe 3' utr of cyclin e1mrna. 25714014_1 over-expression of mir-106b-5p resulted in the decreased mrna and protein levels of setd2 in ccrcc cells. in an setd2 3'-utr luciferase reporter system, mir-106b-5p downregulated the luciferase activity,and the effects were abolished by mutating the predicted mir-106b-5p binding site. 25714014_2 moreover, attenuation of mir-106b-5p induced cell cycle arrest at g0/g1 phase, suppressed cell proliferation, enhanced processing of caspase-3, and promoted cell apoptosis in ccrcc cells, whereas these effects were reversed upon knockdown of setd2. 20600201_1 these mirnas were mir-22, mir-690, mir- 122, let-7a, mir-30d and let-7d summarized in table 1, which also includes their functions ascribed to these mirnas to date. 20600201_3 after the t treatment we found a downregulation of 5 target genes for the mir-22, 1 target gene for the mir-690, 2 target genes for the liver-specific mir-122, 6 target genes for the let-7a/let-7d, and 3 target genes for the mir-30d, as summarized in table 2. there was only one exception: the mir-22 targeted mrna of cyp17a1 . 26337469_1 the results showed mir-212-3p decreased luciferase expression by 37.2%, while the other mirnas did not significantly decrease luciferase expression ,5b, suggesting that rfxap is a target mrna of mir-212-3p. 21553024_1 to understand the mechanism of this process, the expressions of cell-cycle related proteins ccnd1 and cdk6 were determined by western blot analysis. 21553024_2 the results showed that ccnd1 and cdk6 were drown-regulated in hepa1-6 cells transfected with mir-34a mimic, compared with the controls . 21553024_3 mir-34a may arrest hepa1-6 cells in g1 phase by mechanisms that are at least partially dependent on ccnd1 and cdk6. 25963391_1 mir-18a increased the radiosensitivity of cancer cells by targeting the 3'-utr of the atm gene, thereby reducing dsb repair. 25963391_2 mir-18a suppresses atm expression by targeting 3'-utr of atm. the results showed that the level of atm protein was significantly down-regulated following mir-18a overexpression but upregulated when mir-18a was suppressed. 26747772_1 taken together, these results indicate that mir-483-3p directly regulates smad4 expression through binding to its 3'utr. 25395673_2 in addition, the use of mirna mimics and luciferase reporter assays revealed that mirna-26b functions as a proapoptotic factor in porcine follicular gcs by targeting the 3'-untranslated region of the smad4 gene. 20141427_1 in this study, we found that the antisense inhibition of mir-21 in k562 cells suppressed cell migration, promoted cell apoptosis, and inhibited cell growth, and up-regulated the expression of the tumor suppressor gene pdcd4. 21460854_2 these data indicate that mir-155 directly regulates tcf4 expression through 3'-utr interaction. 21460854_3 these data suggest that expression of satb1 is negatively regulated by mir-155 through interaction with its 3'-utr. 21460854_4 figure 7 expression of satb1 is suppressed by stable-expression of mir-155. 21460854_5 mir-155 directly suppresses the expression of tcf4 and satb1 through an interaction with 3'-utr. 21460854_6 we have identified sites located in tcf4 and sabt1 3'-utrs that play a role in the mir155 mediated suppression of tcf4 and satb1 expression. 25370363_1 targetscan was used to search for potential targets of mir-144, and akt3 was identified as a potential target . 25370363_2 mir-144 overexpression significantly inhibited the luciferase activity of the akt3 wt 3'-utr, but not the akt3 mut 3'-utr . in addition, overexpression of mir-144 significantly suppressed the mrna and protein expression levels of akt3. 25370363_3 showed that overexpression of akt3 markedly reversed the suppressive effects of mir-144 on hcc cells. 25147827_1 48 hours after transfection, the expression levels of oct4, nanog, and sox2 in mir-302 group were 1.834, 3.442, and 2.101 times higher than the mock group, respectively . 25147827_2 since brachyury and pax6 were rarely detected in the third-passaged adscs , we only compared the expression level of afp mrna between the mir-302 and mock groups. 25147827_3 afp mrna expression was downregulated in the mir-302 transfected adscs by a mean factor of 0.521 . 22433309_1 the mechanism may be that let-7c represses the expressions of cyclin d1 at both protein and mrna levels. 22396742_2 our results suggest that mir-194 is a key mediator during chondrogenic differentiation via elimination of the effect of transcription factor sox5. the sox5 3'-utr contains one putative mir-194 binding site which is bound with imperfect complementation. 22396742_3 we demonstrated the predicted targetproteins for mir-194 using bioinformatic approaches, we found that one of the targetproteins was sox-5. 22396742_4 these results suggest that mir-194 potentially regulates sox5 expression by binding the mres within the sox5 3'-utr, and prompted us to investigate whether mir-194 affects chondrogenesis via targeting of sox5. 26338045_1 the results indicated that co-transfection with mir-195 in pc-3 and lncap cells significantly decreased luciferase activity when the construct contained the 3'-utr of bcox1 . 26338045_3 taken together, our results indicated that mir-195 can negatively regulate bcox1 expression by directly binding to its 3'-utr. 26755726_1 taken together, our data demonstrate that kdm4a is a direct target for regulation by hsa-mir-23a/b and hsa-mir-137 in rpe cells. 22876303_1 moreover, we show the possibilities that mir-145 modulates p72 expression through its 3' untranslated region and that c-myc downregulation is involved in both p68 suppression and mir-145 induction. 22876303_2 our results suggested the downregulation of p72 by mir-145 through binding to its 3'-utr might be at least one of the molecular basis for the decrease of its expression in the transgenic small intestine tumors. 22876303_3 we demonstrate that the combination of mir-143 and mir-145 inhibits the expression of c-myc in human colon cancer cells, whereas mir-145 retards that of p72. 22876303_4 these results implied that the downregulation of p72 observed in the transgenic small intestine tumors could be at least in part a direct effect of mir-145. 22876303_5 thus, mir-145 might directly bindthe mrna of p72 and restrain the expression of p72. 25609710_1 this indicates that mir-145 binds directly to the 3804- 3810 region in igf1r 3'-utr. 25609710_2 following previous reports that igf1r is a target gene for mir-145 , we have shown that overexpression of mir-145 reduces the level of igf1r protein in endometrial epithelial cells, and identified a target site in the 3'-utr. 25609710_3 quantitative pcr, western blotting and 3'-utr luciferase reporter assays confirmed that igf1r is a direct target of mir-145 in the endometrium. 20470934_1 reporter assays indicated that sirt1 was a direct target of mir-34a. 20470934_2 sirt1 was a direct target of mir-34a, and expressions of sirt1 were downregulated at the posttranscriptional level. 20470934_3 the results showed that overexpression of mir-34a in u251 cells did not change sirt1 mrna expression significantly but decreased protein levels . 20470934_4 it was validated that mir-34a recognized the 3'-utr of sirt1 transcripts and sirt1 was a direct target of mir-34a.these 20470934_5 observations indicated that mir-34a downregulated the expressions of sirt1 at the posttranscriptional level. 23938381_1 fifteen putative targets of hcmv-mir-ul36 were identified using hybrid pcr, one being the hcmv ul138 gene that has previously been identified as a novel latency-associated determinant of hcmv infection.down-regulation of ul138 expression by hcmv-mir-ul36 was validated using luciferase reporter assays and western blot analysis in hek293 cells. 23341351_1 additionally, overexpression of mir-326 led to downregulation of smo, resulted in decreased cell proliferation and elevated rate of apoptosis in cml cd34 cells 20506192_1 we further show that mir-137 target the mind bomb one protein through the conserved targetsite located in the 3' untranslated region of mib1 messenger rna. to further validate the interaction between mir-137 and its targetmib1 3'-utr, we mutated the seed sequence of mir-137 located within the mib1-3'-utr reporter . 20506192_2 taken together, these data suggest that mir-137 regulates the protein expression of mib1 through the 3'-utr of mib1. 26673737_1 moreover, 3'-utr reporter assays showed that hdac-4 is a direct target of mir-222. in summary, we herein report that mir-222 is one of the mirnas responsible for cartilage degradation in human oa chondrocytes, where it targets hdac-4 and thereby alters mmp-13 activity. 23811688_1 lentivirus-mediated overexpression of lin28 in adult hscs elevates their self-renewal activity in transplanted irradiated hosts, as does overexpression of hmga2, a well-established let-7 target that is upregulated in fetal hscs. 23811688_3 together, these findings show that increasing lin28 expression in adult hscs results in an inhibition of let-7 levels and an accompanying increase in hmga2 and igf2bp2 in their primitive progeny, thus mimicking the same pattern of expression of these genes seen in their fetal counterparts. 26676464_1 next, we identified the pik3r1 as a direct target of mir-21 and showed that it was negatively regulated by mir-21. 26676464_2 although a significant reduction in luciferase activity was observed for the wt construct, high luciferase activity was maintained in all of the mutants , thereby supporting the direct interaction between mir-21 and these two targeted regions within the pik3r1 3'-utr. 26676464_3 together, these data support the hypothesis that mir-21 by targeting pik3r1 promotes breast cancer cell growth, invasion and migration. 26676464_4 in the present study, we present evidence that pik3r1 is a direct mir-21 target. 26844700_1 we have shown that ahnak target site is responsive to mir-222 in luciferase reporter assays and that ahnak protein is modulated following mir-222 overexpression and inhibition in muscle cells. 26844700_2 ahnak and rbm24 are novel targets of mir-222 in skeletal muscle cells. 26844700_3 by using rna-induced silencing complex pulldown followed by rna sequencing, combined with in silico microrna target prediction, we have identified two new targets of microrna-222 involved in the regulation of myogenic differentiation, ahnak and rbm24. 26844700_4 these results confirm that mir-222 directly inhibits ahnak and rbm24 target transcripts. 25633044_1 hsa-mir-145 overexpression inhibited the mrna and protein expression of sex-determining region y box 9 in hs 1.tes cells. 26642205_1 further investigation revealed that mir-375 directly targeted the 3'-utr of itpkb mrna and over-expression of mir-375 led to significantly decreased itpkb protein level and promoted cell growth. 26642205_2 in addition, we demonstrate that mir-375 promotes cell growth in sclc cell line and inhibits itpkb expression at the posttranscriptional level by directly targeting the 3'-utr of itpkb mrna. 26642205_3 taken together, the results revealed that mir-375 targeted the 3'-utr of the itpkb mrna primarily through the target site 2 . 26642205_4 the data indicated that mir-375 inhibited the expression of itpkb at the posttranscriptional level by directly targeting the 3'-utr of itpkb mrna. 26642205_5 the luciferase assay revealed that itpkb is the direct target gene of mir-375. 11056047_1 furthermore, the nesp55 region transcripts remain strictly imprinted in tissues that lack gnas-as. 18587408_1 the bace1-antisense transcript regulates bace1 mrna and subsequently bace1 protein expression in vitro and in vivo.expression of bace1-as increases bace1 mrna stability. 18587408_2 this observation suggests that bace1 and bace1-as expression may be regulated concordantly, as was recently shown for other sense-antisense pairs. 18587408_3 moreover, overexpression of bace1-as led to a fourfold increase in bace1 mrna . 18587408_4 when measured by western blotting, the overexpression of bace1-as resulted in increased bace1 protein abundance . 26655271_2 luciferase reporter assay confirmed that let-7g and let-7i combined directly with 3'-utr of abcc10, in consequence, inhibiting abcc10 expression and enhancing cellular sensitivity to drugs. 26655271_3 our results suggested that abcc10 is a genuine target for mir-let-7g/i and we deduced that overexpression of mir-let-7g/i might inhibit cell proliferation and enhance apoptosis of esophagus cancer cells via down-regulating the protein expression of abcc10. 26655271_4 additionally, the present study demonstrates that mir-let-7g/i regulate ddp resistance by targeting abcc10 in esophageal carcinoma cell lines. 21042732_1 bioinformatics and luciferase reporter assays showed that mir-221/222 co-modulated the p53 upregulated modulator of apoptosis expression by directly targeting the binding site within the 3'utr. 21042732_2 together, these findings suggest that puma is a direct target of mir-221/222 that functions as an endogenous apoptosis regulator in these epithelial cancers. 20673989_2 moreover, significantly lower luciferase activity was detected in the cells transfected by the wild-type ctla-4 construct relative to the constructs containing the mutated mir- 155 seed region, indicating that the ctla-4 transcript is a direct target of mir-155 . 20673989_3 intracellular ctla-4 protein levels were measured by means of flow cytometry after transfection with a mir-155 precursor to investigate whether the presence of mir-155 in activated th cells has an effect on ctla-4 protein levels. 24375644_2 furthermore, p-rex2a was identified as a direct target of mir-338-3p, and silencing p-rex2a resulted in the same biologic effects of mir-338-3p expression in gastric cancer cells. 26782545_4 our data showed that mir-96 directly targeted grb2 in cardiomyocytes. 20736365_1 members of the mir-196 family could suppress breast cancer cell migration and metastasis by inhibiting hoxc8 expression. 20736365_2 these results show that members of the mir-196 family inhibit hoxc8 expression through the mechanism of translational repression. 20736365_3 these results support the functional link between mir-196 and hoxc8. 20736365_4 these results thus show that the ratio of mir-196s to hoxc8 mrna, rather than the levels of mir-196s or hoxc8 mrna, reflect the migration status of a particular cell line. 20736365_5 these results suggest that the ratio of mir-196s to hoxc8 mrna may be specifically correlated with the metastasis status of breast tumors. 22496782_1 further, several micrornas, specifically mir-499 and mir-1709 were discovered to influence ptn expression via its 3'-utr which suggests that post-transcriptional regulation influences ptn expression in chickens. 22496782_3 these results indicate that mir-499 and mir-1709 bind directly to the 3'-utr of the ptn transcript and post-transcriptionally regulate ptn gene transcription. 22958478_2 the mir-142-pcdna3.1 and mir-448-pcdna3.1 expression plasmids were first transfected into 293et cells and the expressions of mature mirnas were verified by quantitative rt-pcr . 22958478_3 over-expression of mir-142 but not mir-448 significantly repressed the activity of the bmal1/bmal1 3'-utr-luciferase reporter . 22958478_4 we also found that over-expression of mir-142 could significantly reduce the luciferase reporter rna levels , suggesting that mir-142 was able to accelerate targetmrna degradation. 23024754_1 reporter assays showed that mir-210 inhibited rod1 by the direct binding to this sequence, demonstrating that rod1 is a bona fide seedless target of mir-210. 23024754_2 as expected, both rod1 mrna and protein were down-modulated upon hypoxia in a mir-210 dependent manner. 23024754_3 rod1 targeting by mir-210 was biologically significant: the rescue of rod1 inhibition significantly increased hypoxia-induced cell death. 23024754_4 fig.1b shows that rod1 was as enriched as efna3 and rad52, two well established mir-210 target . 23024754_6 these data demonstrated that rod1 is directly targeted by mir-210. 23024754_7 these data suggest that the anti-apoptotic activity of mir-210 is also mediated by other target besides rod1. 20299512_1 specifically, janus kinase 1 was shown to be a direct target of mir-17. 20299512_2 since jak1 was efficiently down-regulated on mrna as well as on protein level by mir-17 and the closely related mir-20a and we additionally demonstrated that inhibition of mir-17 increased jak1 expression , we further tested the function of jak1 in endothelial cells. 20299512_3 moreover, silencing of jak1 partially reduced the proangiogenic effect mediated by mir-17 inhibitors , indicating that jak1 is one of the mir-17 downstream target. 20299512_4 overexpression of mir-17 reduced luciferase activity but exhibited no effect on a mutated construct , showing that mir-17 directly target the jak1 3'-utr. 26883907_1 taken together, these results suggest that mir-326 inhibitor enhances sensitivity to egfr inhibitor by targeting hdac3. 26415649_1 smad7 and pten, the repressors of smad3-dependent and pi3k-dependent tgf--beta1-signalling respectively, are known targets of mir-21. 26415649_2 ectopic expression of mir-21 in ptcs reduced smad7 protein under basal conditions but also prevented the tgf--beta1-induced increase in smad7 protein . 26415649_3 pten protein was decreased by mir-21. 21546206_1 this study demonstrates the inverse relationship between mir-21 and pdcd4, thus suggesting that mir-21 post-transcriptionally modulates pdcd4 via mrna degradation. 21546206_3 prior to this, despite the perfect complementarity between mir-21 and its targetsite at the 3' -utr of the pdcd4 gene, there had been no convincing data to support the hypothesis that mir-21 downregulates pdcd4 by mrna degradation. 21546206_4 the present study conducted on 49 tumour and 61 normal tissues, clearly demonstrated a strong inverse correlation between mir-21 and pdcd4-mrna expression, thus providing evidence that mir-21 may post-transcriptionally downregulate pdcd4 through the mechanism of mrna degradation. 26271009_1 subsequently, our in vitro study showed that mir-9 directly targets mrnas of lifr-beta, il6st , and jak1 to down-regulate these critical upstream components of the jak-stat pathway, achieving inhibition of stat phosphorylation and consequently, suppression of astrogliogenesis. 26271009_2 this study demonstrated a novel molecular mechanism through which mir-9 mediated the action of ngn1 by suppressing the expression of three major components of jak-stat singling, lifr-beta, il6st, and jak1, which attenuated stat1/3 phosphorylation to inhibit the astrogliogenic differentiation genes or programs. 22569286_1 mir-200c target the expression of zebs, vegfa, flt1, ikkb, klf9, and fbln5 and alters cellular proliferation. 22569286_2 function of mir-200c repressed zebs expression through direct interaction with their respective 3'-utr as determined by luciferase reporter assay. 22569286_3 gain of function of mir-200c repressed vegfa, ikk-beta, and klf9 expression through direct interaction with their respective 3'-utrs , but not with fbln5 3'-utr as determined by luciferase reporter assay. 25323629_1 in addition, metadherin was shown to be a direct target of mir-22 and the expression of mtdh was inversely correlated with mir-22 expression in gastric cancer. 25323629_2 furthermore, it was shown that metadherin was a target gene for mir-22 and regulated the invasion and metastasis of gastric cancer cells. in conclusion, these results indicated that mir-22 downregulated mtdh expression by directly targeting its 3'utr. 22618231_1 mir-21 targeting of jag1 in mda-mb-231 breast cancer cells is dependent on mir-21 dosage . 22618231_2 we demonstrate that jag1 is targeted and its expression levels suppressed by mir-21 in mcf-7 cells, but not in mda-mb-231 cells. 22618231_3 our results indicate that mir-21 can targetthe conserved binding site in the jag1 3'-utr and lead to reduced expression levels in mcf-7 breast cancer cells. in addition, increasing the levels of mir-21 caused a significant decrease in the luciferase activity of pmir/jag1-utr in mda-mb-231 cells , suggesting that increased mir-21 levels induce mir-21:jag1 targeting and that the low endogenous levels of mir-21 in mda-mb-231 cells allow higher jag1 expression levels. 26545119_1 to test the effects of mir-17-92 dependent targeting on smad2 mrna turnover, real-time pcr was performed. 26545119_2 steady-state smad2 mrna levels were not significantly changed in kshv infected tive cells, compared to mock infected cells. 26545119_5 this indicates that the mir-17-92 cluster led to down-regulation of smad2 by mainly inhibiting translation. 26545119_6 in summary, vflip and vcyclin contribute to inhibition of tgf--beta signaling by transcriptionally activating the mir-17-92 cluster, which results in decreased translation of smad2 mrna. 26545119_7 smad2 expression and the response to tgf--beta were restored by antagomir against the mir-17, 18a, and 20. this indicates that the mir-17-92 cluster led to down-regulation of smad2 by mainly inhibiting translation. 22580331_1 in addition, we identified pknox1 as a genuine mir-223 target gene and an essential regulator for macrophage polarization. 22580331_2 for the first time, this study demonstrates that mir-223 acts to inhibit pknox1, suppressing proinflammatory activation of macrophages; thus, it is a crucial regulator of macrophage polarization and protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance. 22580331_3 pknox1 is a bona fide mir-223 target gene that partially mediates its function during macrophage polarization. 22580331_4 consistent with in vitro observations, pknox1 protein levels in the adipose tissues collected from hfd-fed mice were inversely correlated with mir-223 expression levels . 22580331_5 pknox1 is a microrna-223 target. 22580331_6 these results demonstrated that pknox1 is a bona fide target of mir-223 and plays a role in regulating macrophage polarization. 25577249_1 furthermore, we found that cdk6 is a direct target of mir-377 and showed that mir-377 impaired mg-63 cell proliferation through the regulation of cdk6 expression. 25577249_3 these results suggest that mir-377 could affect mg-63 cell proliferation via regulation of its target cdk6. 26807179_1 bioinformatics analyses showed that mir-214 bound to 3'-utr of -beta-catenin mrna in ec cells to inhibit its translation. 26807179_2 together, these data demonstrate that mir-214 targets 3'-utr of -beta-catenin mrna to inhibit its translation in ec cells, and loss of mir-214 in ec may result in increases in -beta-catenin, and subsequently enhanced wnt signaling in ec cells. 26807179_3 together, these data suggest that mir-214 suppresses -beta-catenin protein, but not -beta-catenin gene transcription in ec cells. 25313246_3 we show that cdon expression is regulated by the mir181 mirna family, whose expression is directly associated with neuroblastoma aggressiveness. 21205209_1 we further verified that mir-203 directly targeted 3'-untranslated region of the bcl-w gene, and decreased its expression in vitro and in vivo. 21205209_2 moreover, we observed that ectopic expression of mir-203 decreased the bcl-w protein content in a time-dependent manner in t24 cells . 21205209_3 these observations confirm that mir-203 inhibits endogenous bcl-w in bladder cancer cells. 21205209_4 importantly, fig. 4 shows that bcl-w expression was increased in bladder cancer tissues that showed significantly decreased mir-203 expression. 21205209_5 these data confirm that mir-203, at least in part, inhibited bladder cancer progression by repressing bcl-w. 26787707_1 with the help of bioinformatics analysis, inhibitor of apoptosis-stimulating protein of p53 was identified to be a direct target of mir-140, and luciferase reporter experiment confirmed this discovery. 26052934_1 our results show that mir-16 is able to bind the target site in the range of 8699- 8719 nt from the stop codon in mor-1 mrna 3 ' -utr and suppress the expression of oprm1 gene. 26052934_2 these results suggest a sequence-specific interaction between mir-16 and its binding site in mor-1 mrna 3 ' -utr. 26052934_3 mir-16 inhabits mor-1 mrna 3 ' -utr activity by binding to its target sequence. 26498524_1 moreover, western blot analysis further demonstrated that mir-564 overexpression significantly inhibited the protein levels of zic3 in both a549 and h1299 cells . 26498524_2 zic3 is a direct and functional target of mir-564 in lung cancer cells. 26498524_3 the expression level of mir-564 was negatively correlated with zic3 protein in lung cancer tissues 25769949_1 mir-21 modulates radiosensitivity of hr-hpv cervical cancer cell though directly targeting lats1. 25769949_2 these results suggest that mir-21 can directly target lats1 and regulate its expression. 21182263_1 mir-34a directly target yy1 through a mir-34a-binding site within the 3'utr of yy1. to test the hypothesis that mir-34a directly target yy1, a luciferase reporter using partial yy1 3'utr with mir-34a binding site intact was constructed. 21182263_2 we also constructed a luciferase reporter vector containing the same part of yy1 3'utr but with mir-34a binding site removed . 21182263_3 the resulting reporter constructs were transfected into sk-n-as cells, a nb cell line that does not express mir-34a 5, along with mir-34a or a mimic control microrna. 21182263_4 taken together, these results demonstrated that mir-34a directly target the yy1 gene through binding to yy1 3'utr. 26723394_2 these results confirmed that mir-26b-3p indeed affects esr1 expression. 26723394_3 the results validated that mir-26b-3p regulates the expression of esr1 via directly binding to the cds region of esr1 mrna. 26553452_1 indicating the fact that mir-218 targets cdcp1. 21548940_2 transfection of c4-2b and rwpe-1 cells with let-7d mimic down-regulated the expression of endogenous pbx3 . 21548940_3 the effect of let-7d was blocked by mutating the putative binding site of let-7d in the 3'utr sequence of pbx3 . 21548940_4 the presented results show that androgen regulates pbx3 expression via let-7d in the prostate cancer cell lines tested. 26847706_1 which suggested that cxcl12 is directly targeted by mir-137. 26847706_2 these results indicated that cxcl12 is a direct target of mir-137 in ptc cells. 20798686_2 chemotherapy-induced mir-448 suppression directly target and promotes satb1 expression. 20798686_3 alignment of potential mir-448-binding sites in the 3'-utr of the satb1 mrna of different species. 20798686_4 importantly, antisense inhibition of mir-448 resulted in a moderate but significant increase in the level of endogenous satb1 in mcf7 cells , and this effect was abolished by cotransfection with pre-mir-448 and/or a sirna directed against satb1 . 19638978_1 dnmt3a is the direct targetmir-143. 19638978_2 our data indicated that an enforced mir-143 expression led to a dramatic reduction of dnmt3a expression at both the mrna and protein levels , suggesting a potential regulation of dnmt3a by mir-143. 19638978_3 the relative luciferase activity of the wt construct of dnmt3a 3'-utr in both the colon cancer cells was significantly reduced in the presence of mir-143 , whereas such a suppressive effect of mir-143 on luciferase activity was not observed in both cells with the mut construct of dnmt3a 3'-utr , highlighting a direct and specific interaction of mir-143 on dnmt3a 3'-utr. 21455217_1 in addition, myb can inhibit mir-148a by directly acting on the transcription factor binding site in mir-148a gene and mir-148a can posttranscriptionally silence bcl-2. 21455217_2 the levels of bcl-2 protein were clearly reduced in mir-148a-overexpressing rko and lovo cells compared with control cells . 21455217_3 hence, these data indicate that mir-148a is controlled by the transcription factor myb, and activates the cytochrome c-揷aspase 9-揷aspase 3-揚arp intrinsic apoptosis pathway by silencing bcl-2 posttranscriptionally in colorectal cancer cells. 21455217_4 however, by immunochemistry and immunoblotting techniques, we found similar results corresponding to those observed in vitro, which showed that bcl-2 was expressed less in mir-148a ectopic-expressed xenograft tumours than in controls . 26498873_1 jak2 is a target gene of mir- 101. 22988087_1 in the current study, we report that translational repression of the many and manz genes by sgrs requires a second binding site located in the manx-many intergenic region. 26722252_1 demonstrate the effect of ctd on mir-106b-93 target genes p21 and pten, western blot analysis was performed following 48 h ctd treatment. 26722252_2 p21 and pten have been shown to be mir-106b and mir-93 post-transcriptional targets . 26722252_3 mcf-7 cells exhibited a significant reduction in e2f1, mcm7, mir-106b and mir-93 expression following ctd treatment .4. following confirmation of mir-106b inhibition , p21 and pten protein expression were observed to be increased in mcf-7 cells treated with ctd . 26722252_4 these results suggested that ctd inhibits mir-106b and mir-93 expression, and functions in breast cancer, as indicated by a reduction of its targets, p21 and pten, which are important tumor suppressors in breast cancer. 26432332_1 moreover, phosphatase and tensin homolog , a unique tumor suppressor gene, was confirmed as a direct target of mir-92a, and pten messenger rna expression was decreased in nsclc tissues and was inversely correlated with mir-92a. 26432332_2 taken together, these findings suggested that mir-92a could promote growth, metastasis, and chemoresistance in nsclc cells at least partially by targeting pten. 26432332_3 these results indicate that pten is a mir-92a target in nsclc. in addition, we also found that mir-92a can enhance proliferation, migration, invasion, and chemoresistance of nsclc via targeting the 3'-utr of pten. 23143395_1 we determined whether mir-29c regulates the pten protein by transiently inducing or inhibiting mir-29c in mcf10a cells. 23143395_2 transient overexpression or inhibition of mir-29c resulted in noticeable changes in pten protein levels . 23143395_3 together, these data suggest that mir-29c downregulates pten protein by targeting the pten 3'-utr. 23143395_4 yap appears to directly induce mir-29c to target pten. 23143395_5 the promoters of mir-29a and mir-29b1/2 also contain binding sites for teads , suggesting that yap transcriptionally regulates mir-29 to inhibit pten. 23143395_6 consistent with our observations, an inverse correlation between pten and mir-29 has been reported in hepatocellular carcinoma29. 23143395_7 each mir-29 is sufficient to rescue the effects of yap knockdown on phosphorylation of s6k and s6 . 23143395_8 these data support that the mir-29 family is important for the regulation of pten by yap. 26360780_1 these results suggest that cxcr7 is a direct target of mir-101 in brc cells.. by contrast, downregulation of mir-101 by transfection of 4t1-luc2-nm cells with as-mir-101 increased the activity of a luciferase reporter fused to the wt cxcr7 3'-utr . 20633528_1 mir-122-induced down-regulation of ho-1 negatively affects mir-122-mediated suppression of hbv. 20633528_2 we further found that the down-regulation of heme oxygenase-1 by mir-122 plays a negative role in the mir-122-mediated inhibition of viral expression. 26396534_1 mir-205 has a predicted binding site in the 3'-utr of vegfa. 26396534_2 consistent with the reporter assays, we observed that transfection with mir-205 decreased mrna and protein expression of vegfa relative to the scramble groups . 26396534_3 these findings suggest that vegfa is a direct target gene of mir-205 in os cells. 22381690_1 therefore, tbx1 is a potential target of mir-182. 22381690_2 because tbx1 is a nuclear protein with predominant expression in the nucleus, we hypothesize that mir-182 directly represses tbx1 via seed-match target sites. 22847613_1 here, we identified a novel mechanism by which mutant p53 demonstrates gof effects to facilitate emt and cancer cell invasion by repressing mir-130b, an inhibitor of zeb1. 22847613_3 mir-130b impairs cell invasion by targeting zeb1. 22847613_4 these data together suggest that mir-130b downregulates zeb1 expression in ec cells by destabilizing the zeb1 mrna as well as translational suppression. 22847613_5 transduction of mir-130b caused marked inhibition of the wt zeb1 3'-utr, but had no effect on mutant zeb1 3'-utr . in addition, mir-130b inhibition by anti-mir-130b substantially increased luciferase activities of wt zeb1 3'-utr compared with control anti-mirna . 21836020_1 curcumin induces hypomethylation of the mir-203 promoter and subsequent upregulation of mir-203 expression. 21836020_2 this leads to downregulation of mir-203 target genes akt2 and src that culminates in decreased proliferation and increased apoptosis of bladder cancer cells. 19135980_1 ccne1 is one of direct downstream target of mir-15b. 19135980_2 we found that mir-15b could significantly downregulate ccne1 protein levels but not its mrna levels, suggesting that ccne1 is a potential functional target of mir-15b. 19135980_3 lastly, results from our dual-luciferase reporter assays suggest that ccne1 is one of the functional downstream target of mir-15b. 21618527_1 furthermore, up-regulation of mir-22 could suppress the protein level of pten and reduction of mir-22 level markedly increased the protein level of pten in cardiomyocytes by western blot analysis, suggesting that the contribution of mir-22 to cardiomyocyte hypertrophy may be partially through targeting pten. 21618527_2 using luciferase assay, we showed that overexpression of mir- 22 in 293t cells could significantly suppress the luciferase activity of a reporter fused with 30 utr of pten mrna . 21618527_3 to investigate whether the expression of pten was suppressed by mir-22 in cardiomyocytes, western blot was used to analyze pten protein level. 21618527_4 the results showed that overexpression of mir-22 in cardiomyocytes significantly down-regulated pten expression level, while inhibition of endogenous mir-22 level markedly increased pten protein level . 17344217_1 depression of key k+ channel via repression of erg by mir-133 may contribute to the slowing of myocyte repolarization, and thereby qt prolongation and the associated arrhythmias in diabetic hearts 26082201_1 we identified three mirs, mir-146a, mir-335 and mir-622, regulating the expression of both upar and cxcr4 in aml cell lines. 26177443_1 ergic3 and mir-203a expression were negatively correlated in patients- tissues, similar to that in cultured cells. 26177443_2 the mir-203a mimic treatment increased mir-203a expression 5b and decreased ergic3 expression. 26498144_1 taken together, we concluded that mir-214 was able to directly bind the 3'-utrs of e2f2, cdk3, and cdk6. 21596753_1 we have established the sirt1 transcript as subject to regulation by mir-200a, through mir-200a targeting of sirt1 3'-utr. 21596753_3 4b shows that mir-200a inhibits the luciferase activity of the wild-type sirt1 3'-utr, but mutation of the mir-200a mirna-responsive element within the sirt1 3'-utr abolishes mir-200a action, suggesting that mir-200a target one complementary sequence in the sirt1 3'-utr. in fig. 21596753_4 4d , western blot analysis shows that mir-200a is unable to alter sirt1 protein expression when cells are transfected with sirt1 construct lacking a 3'-utr, supporting that mir-200a reduces sirt1 expression by targeting the sirt1 3'-utr. 21596753_5 these findings further confirmed a functional role for sirt1 in promoting emt-like transformation of mammary epithelial cells as well as establishing a role for mir-200a in inhibiting this process. 21596753_6 in support of our in vitro findings, mir-200a down-regulation in tissue samples of breast cancer correlates with the high levels of sirt1 overexpression observed by immunohistochemistry. 22402125_1 we found a putative mir-29b target site in the snail 3'-utr . 22249264_1 luciferase reporter assays confirmed direct binding of mir-29b to the id1 3'-utr. 22249264_2 these results demonstrate that mir-29b directly inhibits the id1 3'-utr, thereby reducing id1 expression. 22249264_3 figure 2 mir-29b target the id1 3'-utr. 22249264_4 thus, the effect of mir-29b on cell migration and invasion is mainly mediated by id1. 25501203_1 we found negative relationships between mir-486 and forkhead box 1, and mir-133a and serum response factor at all developmental stages, suggesting that forkhead box 1 and serum response factor are potential targets of mir-486 and mir-133a, respectively. 25501203_3 mir-133 is mainly expressed during embryogenesis and promotes muscle cell proliferation by directly repressing the expression of srf. 25501203_5 in addition, foxo1 is a target of mir-486 , and they jointly participate in protein degradation. 25501203_6 the decreasing level of mir-486 with age suggests an increasing expression level of foxo1, which may promote muscle atrophy during the later stages of pig muscle development. 26464659_1 in addition, our results of western blot showed that inhibition of mir-25 significantly increased the protein level of fbxw7, while overexpression of mir-25 significantly reduced the protein level of fbxw7 .3d. these data suggest that fbxw7 is a direct target of mir-25. 24260215_1 furthermore, bioinformatics analysis, luciferase assays and western blot analysis identified -beta-catenin as a direct and functional target of mir-200a. 24260215_2 furthermore, we identified b-catenin as the functional downstream target of mir-200a, and activation of the wnt/b-catenin pathway is responsible, at least partially, for mir-200a-silencing-mediated biological functions in wb-f344 cells. 24260215_3 taken together, our data indicate that ctnnb1 mrna is a direct target of mir-200a, and knockdown of mir-200a could activate, at least in part, the wnt/-beta-catenin signaling pathway in wb cells. 21685371_1 luciferase assays validated a functional binding site for mir-29a in the 3' untranslated region of ski. to analyze the function of mir-29a, we transfected hela cells with 3 different luciferase constructs of ski wild-type 3'-utr and mirna precursor 29a. 21685371_3 figure 2 mir-29a binds 3'-utr of ski and is associated with low ski expression in primary aml cells. 21118966_2 as expected, all 4 tumor cell lines tested with the egr1-3'utr reporter showed 2- to 10-fold decrease in luciferase activity in comparison to the control cells , supporting our hypothesis that mir-183 can potentially regulate egr1. 21118966_3 the modified reporter/mimic combination with perfect base pairing led to significant decreases in reporter activity, confirming the existence of a direct interaction between mir-183 and the 3'utr of egr1 . 21118966_4 these results suggest that mir-183 affects both egr1 mrna transcript levels as well as egr1 protein levels via translational regulation. 26627200_1 furthermore, mir-152 expression could be inhibited by tgf--beta, and the negative post-transcriptionally regulation of mir-152 on hla-g was also demonstrated through gain- and loss-of-function studies. 26627200_2 and, results from luciferase assay showed that hla-g 3'-utr was also negatively regulated by mir-152, while no obvious regulation on mut-hla-g 3'-utr was observed at the same time . 26627200_3 in this study, we validated that hla-g expression was repressed by mir-152 while mir-152 expression was also inhibited by tgf--beta induction in gc cell lines. 21079996_1 direct targeting of mir-138 to two candidate binding sequences located in the 3'-untranslated region of gnai2 mrna was confirmed using luciferase reporter gene assays. 21079996_2 these results suggest that mir-138 regulates gnai2 gene expression, at least in part, by regulating the stability of gnai2 mrna. 21079996_4 3d, ectopic transfection of mir-138 reduced the protein level of gnai2 in um1 cells. 21079996_5 these results suggest that mir-138 regulates tscc cell growth, at least in part, by targeting gnai2. 25078617_1 ectopic expression of mir-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the mir-216b results in increased cell proliferation. 25078617_3 finally, we confirmed that down-regulation of mir-216b in breast cancer is inversely associated with p2x7r expression level. 23390134_1 these findings suggest that mir-101, mir-129-5p and mir-221 may directly affect the expression of fmr1 mrna by targeting their predicted target sites in the fmr1 3- utr. 23390134_2 detailed list of synaptic upregulated putative targets according to targetscan for mir-101, mir-129-5p and mir-221 with their enrichment scores and associated p-values are reported in supplementary material, table s2. 26721233_1 by target prediction analysis and luciferase reporter assay, we observed that mir-98 inhibits the protein expression of wnt1 by directly acting on the 3'-utr of wnt1 mrna. 22479456_1 further bioinformatic analysis identified pdgfra as a direct target of mir-34a and this interaction was experimentally validated. 22479456_2 these findings confirm mir-34a regulates pdgfra transcript through direct interactions with its 3' utr. 22479456_3 our findings indicate that proneural gliomas are specifically characterized by mir-34a downregulation with subsequent derepression of the mirna-檚 downstream target pdgfra, a process that promotes tumorigenesis both in vitro and in vivo. 17957028_1 from this, we conclude that the mir-130a consensus binding sequences in the gax 3'utr mediate the down-regulation of gax by mitogens and proangiogenic factors. 22277001_1 we further demonstrate that mir-125b targeted the 3'-untranslated region of lin28 and reduced the abundance of lin28 at both mrna and protein levels. 22277001_2 these results suggest that lin28 might be regulated by mir-125b and play an important role in mesc differentiation. 22277001_3 these data suggest that the targeting of lin28 by mir-125b is conserved in mescs. 22277001_4 the repression of lin28 during differentiation of mescs is, at least in part, regulated by mir-125b. 22277001_5 these results demonstrate that lin28 is intimately involved in the cell lineage speci- fication of mescs and accounts for the mesendodermal commitment when mir-125b is deregulated. 18413726_1 taken together, these data show that imp-1 protein expression is under control of endogenous let-7. 18413726_2 we also determined that this regulation requires the 3'-utr of imp-1 because let-7 and the lna inhibitor had opposite effects on the expression of luciferase when they were cotransfected into cells together with a fusion construct of luciferase and the imp-1 3'-utr . 18413726_4 mutation of either of these two lcs significantly inhibited luciferase repression by let-7. 18413726_5 c, imp-1 is posttranscriptionally regulated through the 3'-utr by let-7. 18413726_6 taken together, these data show that, similar to hmga2, imp-1 protein expression is under control of endogenous let-7 through targeting lcs in its 3'-utr. 18413726_7 these data suggest that imp-1 is one of the major target of let-7g that regulate growth of these cells and are consistent with let-7g causing growth reduction through reduction of imp-1 expression, which then indirectly affects expression of cell cycle regulators. 19471102_1 mir-125b expression affects the proliferation and apoptosis of human glioma cells by targeting bmf. 25576058_1 moreover, after mutating the two mir-34a target sites within the notch 3- utr in the reporter plasmid, no effect of mir-34a on luciferase signal was observed , indicating that the inhibition of luciferase activity seen in the notch + mir-34a condition is due to direct binding of mir-34a to notch in panc02 cells. 25576058_2 metformin reduced glucose and insulin levels and expression of mir-34a and its direct targets notch, slug, and snail. 26382295_1 the proven or postulated mrna targets of mirna-21 respond to lps by one of 2 distinct patterns: 1 a sharp decrease, followed by a prolonged period of down-regulation ; or 2 an immediate robust rise and subsequent return to baseline with a sustained period of down-regulation . 26382295_2 knockdown of pdcd4 protein levels was shown with pro mirna-21 in raw264.7 cells with and without lps stimulation. 26384136_1 the overexpression of mir-582-5p in sw480 and hct-116 cells both decreased the mrna level of rab27a. 26384136_2 western blotting analysis con铿乺med the corresponding reduction of rab27a protein levels in mir-582-5p transfected cells compared with the control . 26384136_3 all of these indicated that rab27a might be a target of mir-582-5p. . 26384136_4 the results from the luciferase reporter assay demonstrated that mir-582-5p decreased the luciferase intensity of wild-type rab27a-3'-utr, compared with the mir-nc cells. 26753959_1 these results indicate that mir-320 and mcl-1 may play an important role in the progression of cervical cancer. 26753959_2 one of mir-320 binding site was found in the 3'-utr of mcl-1. 26753959_3 these results indicate that mir-320 negatively regulates mcl-1 expression by binding to the 3'-utr of mcl-1. 18347095_2 therefore, the same element that we demonstrated above to present ires activity in the zeb2 rna is also relevant for nat transcription. 18347095_3 we also determined whether expression of the zeb2 nat was determinant for the conservation of the intron in the 5- -utr. 18347095_5 as shown in figure 6b, expression of this nat induced the maintenance of the intron in the 5- -utr of endogenous zeb2 mrna. 18347095_6 these results suggest the levels of the nat control zeb2 5- -utr splicing in these cell lines. 22251626_1 to confirm the fact that 3'utr of ccr7 is a direct target of let-7a, a luciferase assay for the reporter gene expressing the let-7a binding sites of ccr7 3'utr was used. 22251626_2 among the targetproteins, ccr7 showed a significant reverse correlation with let-7a expression, suggesting that ccr7 could be regulated by let-7a in breast cancer cells. 22251626_4 these experiments showed that let-7a regulates ccr7 and cell motility, dependent on ccl21 expressions. 22251626_5 the result suggests that let-7a directly regulates ccr7 protein expression through interaction with the 3'utr of ccr7. 22251626_6 collectively, the data suggest that the zebrafish embryo model can be used to monitor the migration of breast cancer cells in a living animal, and let-7a overexpression or ccr7 silencing could cause a significant reduction in breast cancer cell migration in vivo. 22120719_1 in neuroblastoma cells, mir-27b target the 3' untranslated region of ppargamma and inhibits its mrna and protein expression. in addition, ppargamma protein levels are decreased upon overexpression of mir-27b and increased upon addition of antisense against mir-27b . 22120719_2 lastly, in 10-day old tumors generated by injection of sk-n-as cells in nude mice, ppargamma mrna expression is reduced 3-fold in tumors injected intra-tumorally with mir-27b, but not with the control mirna . 22120719_3 thus, mir-27b inhibits ppargamma expression in neuroblastomas cells. 22120719_4 thus, mir-27b and ppargamma regulate the inflammatory response in neuroblastoma cells. 19826008_3 4a, bdnf, ptpn1, and p4hb were down-modulated following mir-210 overexpression and induced when mir-210 was inhibited . 19826008_4 to this aim, mir-210 seed-pairing sites and the immediately surrounding sequences contained in bdnf, cpeb2, ddah1, ncam1, ptpn1, and xist were cloned downstream of a luciferase open reading frame. 19826008_7 4d shows that mir-210 inhibited the reporter constructs containing an intact mir-210 binding site , whereas this effect was prevented by the deletion of the seed complementary nucleotides . 26252738_2 western blot and qrt-pcr analysis indicated that pik3r3 was significantly downregulated by mir-132 in hcc cells. 26252738_3 mir-132 expression inversely correlated with pik3r3 mrna expression in clinical hcc tissues. 25929465_1 our results indicate that mir-155 directly targets the 3'-utr and inhibits cd1d expression 26823729_1 also, we confirmed that mir-29b could directly regulate the expression of kif1b at the post transcriptional level. 26823729_2 as shown in figure 5a, the fluorescence activity was significantly increased by dysregulation of mir-29b , suggesting that kif1b could be directly regulated by mir-29b. 26823729_3 these results indicated that mir-29b could regulate the expression of kif1b at the post transcriptional level. 26823729_4 moreover, we found that mir-29b promotes cell proliferation, invasion, and apoptosis resistance by repression of kif1b expression. 26282218_3 meanwhile,nrf2 expression was downregulated around 2-fold at mrna level, as well as ho-1 and nqo1 at protein level thereby, it was concluded that nrf2 was negatively modulated by mir-34a, including both nrf2-3 ' utr activity and nrf2 expression. 18417479_1 mir-210 inhibits efna3 expression directly. 18417479_2 we determined that one relevant target of mir-210 in hypoxia was ephrin-a3 since mir-210 was necessary and sufficient to down-modulate its expression. 18417479_3 moreover, luciferase reporter assays showed that ephrin-a3 was a direct target of mir-210. 18417479_4 afterward, it was investigated whether mir-210 up-regulation in the absence of hypoxia regulated efna3 levels. 18417479_5 we found that efna3 protein staining was strongly diminished in mir-210-overexpressing cells in the absence of efna3 mrna regulation . 24931160_1 targeting sites of mir-146b in the klf7-3'-utr and direct interaction between mir-146b and the klf7-3'-utr. 24931160_2 overexpression of mir-146b directly inhibits klf7 mrna expression via interaction with its 3'-utr region. 26333672_5 13.0 analyzed that the expression of znf148 and klf4 were positively correlated with the expression of mir-34c. 26333672_6 however, mir-34c had a significant negative correlation with pdgfra , suggesting that pdgfra gene may be a true target gene of mir-34c. 26333672_7 furthermore, the detected protein expression of pdgfra show that it is differentially expressed at different developmental stages of testis, which is consistent with the results detected by fluorescence quantitative pcr. the following results of immunohistochemistry sections showed that the expression levels of pdgfra in 2-days and 3-month were significantly higher than in 4-months and 5-months, which is consistent with the earlier results and provided further evidence that pdgfra was a target gene of mir-34c. in addition, the expression of mir-34c was upregulated rapidly indicating that mi-34c was important for the growth of seminiferous tubules. 26221902_2 therefore, these results highlight the significance of mir-206 as a tumor suppressor in lscc growth in part by targeting cyclind2. 26641802_1 in vitro studies confirmed that lentivirus-mir-33 overexpression repressed both abca1 and abcg1 in cultured murine alveolar macrophages. 26641802_2 bal cells of sarcoidosis patients also displayed elevated mir-33 together with reduced abca1 and abcg1 mrna and protein compared to healthy controls. 26641802_4 findings suggest that alveolar macrophage mir-33 is upregulated by pro-inflammatory cytokines and may perpetuate chronic inflammatory granulomatous disease by repressing anti-inflammatory functions of abca1 and abcg1 lipid transporters. 26694763_2 our study results suggest a direct interaction between mir-185 and stim1 mrna in microvascular endothelial cells. 26694763_3 these results suggest that mir-185 specifically binds to the 3'-utr of stim1 mrna. 26694763_4 these data confirmed that endogenous stim1 expression was negatively regulated by mir-185 in microvascular endothelial cells. 20563308_1 therefore, mir-263b and mir-263a can each act directly via these sites to regulate hid mrna levels. 20563308_2 taken together these experiments provide evidence that mir-263a acts directly via the sites identified in the 3' utr to regulate hid mrna levels in vivo. 19542014_2 recently, we have found that microrna mir-145 is the most abundant mirna in normal vascular walls and in freshly isolated vsmcs; however, the role of mir-145 in vsmc phenotypic modulation and vascular diseases is currently unknown. 19542014_5 vsmc differentiation marker genes such as sm alpha-actin, calponin, and sm-mhc are upregulated by premir-145 or adenovirus expressing mir-145 but are downregulated by the mir-145 inhibitor 2'ome-mir-145. 19542014_6 we have further identified that mir-145-mediated phenotypic modulation of vsmcs is through its target gene klf5 and its downstream signaling molecule, myocardin. 19542014_7 finally, restoration of mir-145 in balloon-injured arteries via ad-mir-145 inhibits neointimal growth. 26718216_1 crct1 expression was inversely correlated with the levels of microrna-520 g in escc tissues, and crct1 was identified as a direct target gene of mir-520 g in escc cells. 26718216_2 crct1 was identified as a direct target gene of microrna-520 g in escc cells, and mir-520 g suppression showed a similar tumor inhibitory effect as crct1. 26718216_3 these results indicated that crct1 is directly regulated by mir-520 g in escc cells. 26718216_4 a significant negative correlation between mir-520 g and crct1 expression was observed in escc tissues;furthermore,a luciferase reporter assay confirmed that crct1 is directly regulated by mir-520 g 22701667_1 using a luciferase reporter assay, we verified the numbl 3'-utr as a direct mir-34a target together these results implicate numbl as a physiologically relevant target of mir-34a in npc, allowing for enhanced notch signaling and inhibition of neuronal differentiation. 22701667_2 collectively our results show that mir34a operates as a regulator within the notch pathway in npc, where it directly target numbl transcripts. 26238857_1 fig. 3 pten and p21 are targets of mir-106b. 26238857_2 the results further confirmed that pten and p21 are direct targets of mir-106b. 26238857_3 our findings indicated that p21 was also a direct target of mir-106b. 26238857_4 the results showed that the expression of mir-106b inversely correlated with pten in colorectal cancer and normal colonic tissues, which further supported the finding that pten is a direct target of mir-106b in vivo. 26231797_2 rnf31 mrna expression were dramatically inhibited in mir-503 transfectants as compared with control cells . 21360794_1 the specificity and significance of pluc-sox2 repression demonstrates that the mir-182 binding site is functionally accessible and suggest that sox2 is a bona fide hair cell mir-183 family member target gene. 21360794_2 figure 6. coexpression and validation of sox2 as a target of mir-182. 25504627_1 these results suggest that hsa-mir-21-3p inhibits human hdac8 expression by directly binding its 3- utr. 25504627_2 western blots showed that mir-21-3p mimic transfection significantly reduced hdac8 level, and mir-21-3p inhibitor increased hdac8 level in primary cardiomyocytes and h9c2 cells . 25504627_3 moreover, in tac mice, hdac8 protein level was reduced in raav9-mir-21-3p-treated group and raav9-anti-mir-21-3p treatment reversed this effect . 21912701_1 3'utr of dio1 is a direct targetfor mir-224 and mir-383. 21912701_2 these data show that endogenous dio1 mrna expression in caki-2 cells is modulated by mir-224. 21912701_3 taken together, these data show that the 3'-utr of dio1 contains specific binding sites for micrornas mir-224 and mir-383. 21912701_4 figure 4 the dio1 3'-utr is the direct targetfor mir-224 and mir-383. in summary, we demonstrated that dio1 3'-utr is targeted by two micrornas: mir-224 and mir-383. 21912701_5 mir-224 mediates loss of dio1 in renal cancer, what results in decreased intratumoral t3 concentration. 25230140_2 mir-135a inhibition markedly restored bcl-2 expression and protected a549 cells from lps-induced apoptosis. 26077989_1 finally we provide experimental evidences showing that mir-17 directly targets the 3- utr of trim8 and post-transcriptionally represses the expression of trim8. 26077989_2 finally we showed that mir-17 directly targets the 3'-utr of trim8 and post-transcriptionally represses the expression of trim8. 26077989_3 collectively, these results indicated that the 3'-utr of trim8 is targeted by mir-17. 26077989_4 overall these evidences demonstrate that mir-17 regulates trim8 expression at both transcriptional and post-transcriptional level by directly binding the 3'-utr region of trim8. 21354414_1 these results suggest that smad3 but not smad4 or smad5 is a major target gene of mir-23b in brl-3a cells. 21354414_2 to assess whether the regulation of smad3 is direct, we fused the 3'-utr region of smad3 to a luciferase reporter to validate the effects of mir-23b mimics on wild type and mutant plasmids . 21354414_4 these results suggest that up-regulation of mir-23b partially inhibited tgf--beta1-induced apoptosis in brl-3a cells by inhibiting the expression of smad3. 26676187_1 experiments were carried out to determine whether mir-210 can regulate the expression of yes1 protein in hcc. in the hcc samples, tumors with higher expression of mir-210 showed consistently lower expressions of yes1 compared to the corresponding paired non-tumor samples . 26676187_2 the decrease of yes1 protein expression was reversed by pre-treatment with mir-210 inhibitor 5e indicating that yes1 is indeed a target of mir-210. 26829385_1 therefore, mir-20a and mir-20b regulated rb1cc1/fip200 expression by targeting the above described mirna-binding sequences in the 3- utr region of rb1cc1/fip200 mrna. 26829385_2 these results demonstrated that rb1cc1/fip200 was the target of mir20a and mir20b for autophagy inhibition. 26829385_4 6. rb1cc1/fip200 expression was negatively correlated to mir-20a and mir-20b expression in breast cancer cells mcf7 and mda-mb-231 and in clinical breast cancer tissue. 22876840_1 our analysis showed that mir-196a suppressed the expression of hoxa5 both at the mrna and protein levels, and luciferase assays confirmed that mir-196a directly bound to the 3'untranslated region of hoxa5. 22876840_2 our findings indicate that mir-196a is significantly up-regulated in nsclc tissues, and regulates nsclc cell proliferation, migration and invasion, partially via the down-regulation of hoxa5. 22876840_3 microrna-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting hoxa5. 26768613_1 we concluded that mir-381 inhibited eoc cell proliferation, migration, and invasion, at least in part, via suppressing yy1 expression. 26768613_2 we also identified transcription factor yy1 as a target of mir-381. 26768613_3 collectively, these resultsindicated that mir-381 inhibited the expression of yy1 by targeting its 3- - utr region. 26768613_4 our functional study on yy1 further supported its role as a target for mir-381, as knockdown of yy1 almost perfectly mimicked the phenotype on cell proliferation, cell migration, and cell invasion induced by the overexpression of mir-381. 23028803_1 p21 and bim, which were identified as targetgenes of mir-106b-93-25 cluster, increased in tsa treated tumor cells and were responsible for cell cycle arrest and apoptosis. 23028803_2 thus our studies strongly indicated tsa inhibited emc cell growth and induced cell apoptosis and cell cycle arrest at least partially through the down-regulation of the mir-106b-93-25 cluster and up-regulation of it's targetgenes p21 and bim via myc. the mir-106b-93-25 cluster downregulates the expression of p21 and bim. 23028803_3 thus, p21 was directly regulated by mir-106b through the 3'-utr, while bim was directly regulated by mir-25. 23028803_4 we also measured the mrna and protein levels of p21 and bim after mir-106b and mir-25 overexpression. 23028803_5 the p21 mrna level was reduced by the mir-106b duplex, and the same change was detected at the protein level . 25026294_2 the proto-oncogene c-myc was identified as a direct target of mir-451, and re-expression of mir-451 inhibited survivin and rad-51 expression by reducing the amount of c-myc protein binding to their promoters. 25585946_1 mir-126 inhibits cell proliferation and induces cell apoptosis of hepatocellular carcinoma cells partially by targeting sox2. 25585946_3 through restoring the expression of sox2 in mir-126-transfected hepg2 cells, we found that overexpression of sox2 could partially abrogate the mir-126-mediated suppression of cell growth. 25585946_4 thus, our data identified mir-126 as a tumor suppressor in hcc through, at least partially by targeting sox2. 23183523_4 3a overexpression of mir-133a resulted in a significant decrease of col1a1, col5a3 and other target collagens, while col7a1, which is not a predicted target for mir-133a, was not regulated . of note, this effect of mir-133a on the expression of col1a1 and col5a3, the collagens with the most abundant regulation upon mir-133a transfection in primary cells, could be confirmed in mir-133a transfected immortalized human hsc and the murine grx cell line . 23183523_5 in these cells, overexpression of mir-133a resulted in a dose-dependent and significant decrease in expression of col1a1 and col5a3, while transfected scrambled mirna had no effect on the expression of these genes. 23932924_1 microrna-106a induces multidrug resistance in gastric cancer by targeting runx3.mir-106a 19252524_4 introduction of mir-449a into pc-3 prostate cancer cells resulted in cell-cycle arrest, apoptosis and a senescent-like phenotype. 19252524_6 using a luciferase 3'-utr reporter system, we established that hdac-1 , a gene that is frequently overexpressed in many types of cancer, is a direct target of mir-449a. 19252524_7 further, our data indicate that mir-449a regulates cell growth and viability in part by repressing the expression of hdac-1 in prostate cancer cells. 26277787_1 src kinase signaling inhibitor 1 was identified as a direct target of mir-211. 26277787_2 additionally, we identified src kinase signaling inhibitor 1 as a direct target of mir-211. 26277787_3 additionally, we identified srcin1 as a direct target of mir-211. 19949084_1 specifically, e-selectin and icam-1 are target of tnf-induced mirnas mir-31 and mir-17-3p, respectively. 19949084_2 mir-31 regulates tnf-induced sele expression by targeting the sele 3'-utr. 19949084_4 analyze the effect of mir-31 on sele protein expression, huvecs were transfected with mir-31 mimic for 12 h; after a 24-h recovery period, they were stimulated with tnf for 3 or 6 h, the peaks of sele mrna and protein expression, respectively . 19949084_5 by immunoblotting, m-mir-31 reduced tnf-induced sele levels by ≈35% at 3 h . 19949084_6 furthermore, sele levels increased by 25% and 20% at 3 and 6 h, respectively, when cells were transfected with an antisense mir-31 inhibitor prior to tnf stimulation . 19531230_1 the target of mir-433 and mir-9 were tumor-associated proteins grb2 and rab34 respectively. 19531230_2 mir-9 and mir-433 down regulated luciferase activity of rab34 and grb2. 19531230_3 a, mir-9 regulated luciferase activity by integrating the binding site in the 3'-utr of rab34. 19531230_4 b, mir-433 regulated luciferase activity by integrating the binding site in the 3'-utr of grb2. 19531230_5 mir-9 and mir-433 down regulated rab34 and grb2 expression in sgc7901 cell line. 26831618_1 taken together, these results indicated that reciprocal expression of zeb1 and mir-205/200c contributed to the phenotypic change. 21474672_1 figure 2 endogenous mir-142-3p directly targets il-6 3- utrs in dcs. 21474672_2 because only constructs a and b were as functional as the wt reporter, these data collectively indicate that only the site specific for mir-142-3p is critical for the regulation of il-6 3'-utr by the endogenous mirs. 21474672_3 these data demonstrate that mir-142-3p directly targets and regulates il-6 3'-utr in dcs. 25479763_1 the pcdna3.1 -mir-223 vector efficiently suppressed the expression of hsp90b1, while silencing mir-223 increased expression of hsp90b1. 23526568_1 these data indicated that bcl2l2 is directly and negatively regulated by mir-195 in ht29 and lovo cells. 23526568_2 these data highlighted that mir-195 interacts with the bcl2l2 mrna and represses its expression especially through the first binding site. 23526568_3 these results suggest that mir-195 play an important role in regulating doxorubicin chemosensitivity directly through adjustment of anti-apoptosis activity by targeting bcl2l2 in colon cancer cells. 23526568_4 our study demonstrated that suppression of mir-195 leads to elevation of its direct targetgene bcl2l2 expression therefore makes the human colon cancer cells more resistant to doxorubicin. 23526568_5 bcl2l2 is a direct target of mir-195, which specifically interacts with the first potential binding site of bcl2l2 mrna 3'-utr. 23526568_6 mir-195 has a modulator effect on bcl2l2 expression and pro-apoptosis activity, which play important roles in regulating doxorubicin chemosensitivity in colon cancer cells. 26786313_1 these results indicate that ethanol-induced reductions in the expression of mir-494 may increase the mrna levels of cited2, cbp, and p300 in the amygdala and regulate anxiolytic-like effects. 21159815_1 these assays point to sugarbabe as a functionally important mir-14 target in the ipcs. 21159815_2 this indicates that endogenous levels of mir-14 are sufficient to negatively regulate gene expression via the sugarbabe 3'-utr in the ipcs in vivo. 21159815_4 because s2 cells endogenously express mir-14, we asked whether depleting mir-14 would lead to elevated expression of the luciferase reporters. 21159815_5 these results suggest that mir-14 can act directly via the predicted target site to regulate sugarbabe levels. 23028672_1 finally, we utilized both luciferase reporter assay and western blot analysis to identify bnip3 as a direct target of mir-145. 21062975_1 mir-302-mediated antiproliferation functions through cosuppression of cdk2, cyclin d1/d2, and bmi-1. 21062975_3 we found that mir-302 over a certain threshold concentration is able to inactivate both complexes through simultaneous suppression of cdk2 and cyclin d1/d2 activities. 21062975_5 different cellular conditions may affect the way of mirna-mrna interaction to change the preference of mirna-mediated gene targeting. 21062975_6 however, there is currently no report related to either the dose-dependent effect of mir-302 or the stringency of mir-302-targetinteraction. our study provides important insights on these issues and, for the first time, revealed that mir-302 functions differently between humans and mice. 20029046_2 our data showed that retinoic acid induction in nb4 cells led to up-regulation of mir-223 and down-regulation of e2f1 protein . 20029046_3 we also tested the ability of mir-223 in down-regulating e2f1 protein levels. 20029046_4 overexpression of mir-223 resulted in a 70% decrease in e2f1 protein levels . 20029046_5 altogether, these results suggest that e2f1 is a potential target of mir-223. 20029046_6 the finding from mir-223 null animals together with our finding that mir-223 target e2f1 and inhibits myeloid cell-cycle progression suggest that down-regulation of e2f1 by mir-223 could be a critical step in granulocytic differentiation. 26845040_1 in addition, apn depressed the elevated expression of connective tissue growth factor , a direct target of mir-133a, through the ampk pathway. 26371161_2 exogenous mir-141 inhibits icam-1 expression on huvecs following tnf stimulation. 18573883_2 since the putative hsa-mir-519c site has been validated for abcg2 3'-utr in s1 cells, we repeated the 3'race assay, using s1 cells transfected with the specific hsa-mir-519c inhibitor. 18573883_3 we used the specific hsa-mir-519c inhibitor to increase the level of abcg2 3'-utr in s1 cells and subsequently confirmed the long sequence in s1 cells and its absence in s1mi80 cells with a nested pcr 1 and nested pcr 2 . 18573883_4 interestingly, the perfect pairing of hsa-mir-519c with the hsa-mir-519c complementary sequence led to the most substantial degradation of abcg2 mrna. 20299448_1 we demonstrate a direct role for mir-23a/b in the dramatic postnatal down-regulation of cugbp and etr-3-like factor proteins that regulate nearly half of developmentally regulated splicing transitions in the heart. 20299448_2 there are three conserved mir-23a/b seed matches in the 3'-utr of cugbp1 and two in cugbp2 . 20299448_3 these data indicate that postnatal up-regulation of mir-23a/b suppresses cugbp1 and cugbp2 protein expression in adult hearts via direct binding to their respective 3'-utrs, resulting in a physiological shift in the alternative splicing of a subset of splicing events. 20299448_4 these results demonstrate a direct functional interaction between mir-23b and each of these regions within the 3'-utr of cugbp1 and cugbp2. 26823753_1 serum and glucocorticoid regulated protein kinase 3 was predicted as the target gene for mir-155, and mir-155 expression was negatively correlated to sgk3 expression. 26823753_2 consequently, mir-155 was overexpressed in cells to verify sgk3 expression, and results showed that mir-155 could negatively regulate sgk3 expression endogenous , which indicating that sgk3 was the direct target for mir-155. in conclusion, the data presented in this study suggested that mir-155 down-regulation played pivotal roles in inhibiting neuropathic pain through targeting sgk3 gene. 25879024_1 besides, the expression level of mir-21 and its potential target sox-2 were also detected 3 days after osteogenic induction; the results showed that sox-2 decreased as the increase of mir-21 abundance, indicating that there was a negative correlation between mir-21 and sox-2 . 21219636_1 these results suggest that mir-21 directly target ankrd46 in bc cells. 21219636_2 ankrd46 3' utr showed a reduction to 54.8% of total luciferase reporter activity, in presence of mir-21, but eif4a2 3' utr did not display significant reduction of luciferase levels, compared with the mir-control . 21219636_3 these results suggest that mir-21 directly target ankrd46 in bc cells. in addition, ankrd46 is newly identified as a direct target of mir-21 in bc. 25620738_1 to confirm these findings, hbx and mirna-30a were coexpressed in hepg2 cells, and the results showed significant inhibition of autophagosome formation and beclin-1 and c-myc expression, 25868860_2 these data verify that sox17 induces mir-371-5p expression and consequently suppresses its direct target sox2. 26299922_1 thus, these results confirmed that notch1 was a direct target of mir-139-5p in breast cancer cells. 26299922_2 these data suggest that downexpression of mir-139-5p increases the chemosensitivity to docetaxel to induce apoptosis via notch1 targeting in breast cancer cells. 26299922_3 taken together, these results also demonstrate that notch1 is a direct and functional mediator of mir-139-5p. 26299922_4 these data further confirmed that mir-139-5p targets notch1. 23873935_1 puma is a target of mir-149. in follow-up functional analysis, our results showed that the mir-149 suppressed apoptosis through targeting the pro-apoptotic protein puma. 23873935_2 these data indicate that mir-149 directly regulates puma expression, and the snp rs71428439 is able to influence the effect of pre-mir-149 on the expression levels of puma. 26044523_1 mir-24-3p directly targets and inhibits p27kip1 protein expression. 26044523_2 mir- 24-3p directly targets the 3'utr of p27kip1 and suppresses its expression. 20620960_1 conversely, the inhibition of endogenous mir-200 in hct116 cells with anti-mir lna200 led to an increase in fap-1 and a decrease in e-cadherin expression , strongly suggesting that mir-200c directly target fap-1. 20620960_2 interestingly, fap-1 mrna levels did not change with the introduction of mir-200c or with the inhibition of mir-200 as determined by semi-quantitative rt-pcr . 20620960_3 therefore, fap-1 is a target of mir-200c, and regulation of fap-1 is due to translational repression and not mrna degradation. 20620960_4 this indicated that the mir-200c effect on cd95 directed apoptosis is mediated by repression of fap-1. 23754622_1 to determine whether these sites can be targeted by mir-124, we cloned luciferase reporter constructs encompassing either 1,410 bps of the mouse usp14 3'-utr or 257 bps of mouse usp24 3'-utr that contain the mir-124 binding sites . 23754622_2 fig. 4 mir-124 suppresses expression of reporter constructs containing 3- utr sequences from mouse usp14 and mouse usp24. in contrast to rat neurons, hek cells lack endogenous mir-124 expression , and as mentioned, the human usp14 sequence has two additional mir-124 binding sites; this most likely add to the more pronounced suppression of usp14 by mir-124 observed in the human cell line. 22867989_3 pre-mir-126 strongly reduced the expression of p85-beta bearing its 3'-utr compared to pre-mir-scramble, but did not modify the expression of p85-beta lacking its own 3'-utr . 22867989_4 these results were also confirmed in ec transfected with the lna-anti-mir-126, which showed a higher amount of p85-beta protein compared to ec transfected with control lna . 21971048_1 we recently demonstrated that the 3'-untranslated region of erbb-2 mrna contains two specific targetsites for binding of the microrna mir-331-3p and that mir-331-3p represses erbb-2 expression and signaling in pca cells. 21971048_2 our previous work indicated that mir-331-3p regulates erbb-2 expression in pca cells via its interaction with two specific targetsites in the erbb-2 3'-utr , one of which is immediately distal to the erbb-2-ure . 21971048_3 we investigated whether hur could antagonize the ability of mir-331-3p to down-regulate erbb-2 expression in pca cells. 21971048_4 thus, hur binding to the wild-type erbb-2 ure does not prevent mir-331-3p binding to its adjacent seed , although the spacing between the two sites may be critical for the regulatory outcome . 21971048_5 this result indicates that loss of hur binding to the erbb-2 3'-utr ure increases the repressive action of mir-331-3p upon erbb-2 mrna. 21347332_1 interestingly, the 3'-utr of the rhob mrna was found to contain one predicted binding site for mir-21 conserved between several species , which suggest that rhob might be a direct target of mir-21. 21347332_2 moreover, rhob was reported very recently to be targeted by mir-21 in hepatocellular carcinoma cell lines. 21347332_3 in huvecs, overexpression of mir-21 significantly decreased the level of rhob mrna expression . 21347332_4 by contrast, inhibition of mir-21 expression increased rhob mrna. 21347332_5 taken together, these results indicate that mir-21 regulates the expression level of active rhob in endothelial cells. 21347332_6 altogether these data confirmed the mir-21-dependent regulation of rhob and its implication in the migrating properties of huvecs. 26175947_3 these data suggested that mir-497 bound directly to specific site in the 3'-utr of ikk-beta mrna. 26175947_4 next, it was determined whether endogenous expression of ikk-beta could be downregulated by mir-497. 26175947_5 to address this issue, western blot analysis was used to evaluate the expression of ikk-beta at the protein level after transfection with mir-497 mimics and nc inpc3-ar cells. 26175947_6 the results showed that the overexpression of mir-497 significantly decreased the expression levels of ikk-beta protein . 26175947_7 collectively, these luciferase and western blot results showed that mir-497 acted as negative regulators of expression of ikk-beta. 22068596_1 in addition, we show that the histone lysine-specific demethylase 1 , a transcriptional co-repressor of nuclear receptor tlx, is a downstream target of mir-137. 22068596_2 these results indicate that mir-137 represses lsd1 expression through the predicted targetsite in the lsd1 3'-utr. 22068596_3 the expression of lsd1 is reduced dramatically in mir-137-rfp-electropoarted cells, compared to control rna and rfp-electroporated cells , providing in vivo evidence that mir-137 target lsd1 expression. 22068596_4 these results strongly suggest that mir-137 regulates neural stem cell proliferation and differentiation in embryonic brains through targeting lsd1 expression by base-pairing to its 3'-utr. 26823769_1 in this study, we have confirmed that, as the myocardial hypertrophy gene, mtor was a target gene of mir-96, who would promote the occurrence of myocardial hypertrophy. 26823769_2 next, we implemented fluorescent report carrier assay for deep analysis and finally confirmed that mir-96 was directly binding to 3'-utr of mtor . 26823769_3 overall, we can conclude that mtor is the direct target gene of mir-96. 26823769_4 by using bioinformatics method and the fluorescent report carrier assay, we finally identified that mtor was the target gene of mir-96. 25530976_1 among them, mir-182 related to the insulin resistance by modulating foxo1 and pi3k/akt cascade and had the greatest copy number in the whole blood.mir-182 23518389_1 these results suggest that mir-31 was able to binddirectly to creg and regulate its expression.these 23518389_2 results suggest that creg is a functional targetgene of mir-31, and is involved in mir-31-mediated vsmc phenotypic modulation. in the present study, computational analysis suggested that mir-31 bound the creg mrna 3'-utr. 23518389_3 the negative correlation between creg expression and mir-31 expression in vsmcs stimulated by either pdgf or serum starvation indicated that mir-31 could potentially regulate the creg gene in vsmcs. 23518389_4 we confirmed that creg protein levels were regulated by the mir-31 mimic and inhibitor in cultured vsmcs. 23544605_2 microrna expression changes in cvb3-infected mice were analyzed by real-time pcr and mir-21 was found to be the mirna whose expression was significantly reduced. 26840372_2 correlation analysis in crc tissues revealed negative correlation between mir-497 and vegf-a expression . 26840372_3 our results indicate that mir-497 targets and full-length wild-type vegf-a 3'-utrs reduced relative luciferase activity only when mir-497 was present . 26840372_4 these results demonstrate that vegf-a mrna is a specific target of mir-497 in hct116 crc cells. 26840372_5 figure 3. vegf-a is a direct and functional target of mir-497. 23348698_1 further studies demonstrated that mir-206 could suppress gc cells proliferation at least partially through targeting the cyclind2 . 23348698_3 although ccnd2 expression has been reported to be the repressed by mir-206 in rhabdomyosarcoma, our luciferase reporter assays demonstrated that ccnd2 was target gene of mir-206 in gc. 23348698_4 these data supported the hypothesis that ccnd2 is direct target of mir-206. 24644030_1 mir-494-3p could bind to the seed sequences in the 3'-utr of the cxcr4 gene. 26656176_1 fig. 3. ezh2 is a direct target gene of mir-340. 26656176_2 these data suggest that the up-regulation of ezh2 and the down-regulation of mir-340 are clearly involved in lscc progression. 26656176_3 taken together, these data strongly reveal that mir-340 directly targets ezh2 expression in hep-2 cells. 26656176_4 accordingly, these results support the hypothesis that mir-340 may act as a tumor suppressor through elevating tumor suppressor gene p27 expression and suppressing pi3k/akt signaling activation by targeting ezh2 expression, resulting in an inhibition of lscc progression. 25222737_1 down-regulation of the tir1 and afb2 receptors by mir393 26776158_2 additionally, we found that mir-29b targets the 5-hydroxymethylcytosine dioxygenase, tet1 for downregulation and has downstream effects on tet1-mediated epigenetic modifications. 26776158_3 taken together, these results indicate that mir-29b targets tet1 for downregulation through an interaction with the tet1 3'-utr. 26776158_4 we provide mechanistic evidence that mir-29b directly downregulates tet1 expression . 26293467_3 in this study, we demonstrate that mir-15b/16 promotes vsmc contractile phenotype, at least in part, by targeting yap, and therefore, restoring expression of mir-15/16 would be a potential therapeutic approach for treatment of proliferative vascular taken together, these data indicate that mir-15b/16 promotes sm contractile phenotype through directly targeting yap. 26386726_1 interestingly, over-expression of mir-31 mimic in a2780 cells leads to a significant decrease in kcnma1 mrna levels . 26386726_2 this was also reflected in a decrease in kcnma1 protein levels , suggesting that mir-31 is able to inhibit the expression of the kcnma1 gene. 20460403_1 rhob is directly targeted by mir-21. 20460403_2 western blot analysis of rhob expression revealed that knockdown of mir-21 led to an increase of 10%, 80%, and 20% in rhob protein expression in huh-7, hepg2, and mda-mb-231 cells, respectively . 20460403_4 this increase was comparable with mrna rhob level induced by mir-21 inhibitor treatment . 15466020_1 the gady gene was shown to overlap the 3 end of the gadx gene, and this overlap region was found to be necessary for the gady-dependent accumulation of gadx mrna. 15466020_2 we suggest that during stationary phase, gady forms base pairs with the 3 -untranslated region of the gadx mrna and confers increased stability, allowing for gadx mrna accumulation and the increased expression of downstream acid resistance genes. 25305490_1 overexpression of let-7i injurkat cells significantly suppressed igf1r expression, which mimicked the actionof igf1r sirna. 18056431_1 when overexpressed, mir-34 leads to apoptosis or cellular senescence, whereas reduction of mir-34 function attenuates p53-mediated cell death. 26151470_2 the mir-153 target site in the 3'-utr of bmpr2 is highly conserved among vertebrates. 26151470_4 mir-153 suppresses osteogenic differentiation by targeting bmpr2. 26314494_1 herein, we first observed ar/mir-190a/yb-1 forms an auto-regulatory negative feedback loop in prostate cancer: mir-190a expression was down-regulated by ar activation; yb-1 functions are as an ar activator; mir-190a inhibited ar expression and transactivation through direct binding to 3'-utr of yb-1 gene. 26314494_3 4b,c, overexpression of mir-190a inhibited yb-1 wild-type, but not mutant luciferase reporter activities in lncap and 22rv1 cells, indicating that mir-190a specifically targets yb-1 through direct 3'-utr binding. 20372781_1 furthermore, our findings suggest that pdcd4 mrna is negatively regulated by mir-21 in gastric cancer and may serve as a targetfor effective therapies. 20372781_3 4a and b,we found an inverse correlation between pdcd4 mrna and mir-21 in gastric cancer cell lines . 26102366_1 then, the same assay was performed for another reporter plasmid containing mutated akt2 3'-utr in mir-137 binding sites. 26102366_2 as expected, the inhibition of luciferase activity by mir-137 was partly removed with binding site 1 or binding cite 2 mutant and almost abolished in the akt2_mut double mutant, suggesting that the conserved region was fully responsible for mir-137 function. 26102366_4 we analysed the protein levels of akt2 in 12 gc patientsin whom mir-137 was down-regulated. 24472409_1 using western blot analysis, mir-21 knockdown enhanced the expression of tumor suppressor pdcd4, and attenuated apoptosis inhibitor c-iap2. 18413822_2 furthermore, our findings suggest that hmga2 is negatively regulated by the let-7 mirna family in human gastric cancer. 24178239_1 our results demonstrated that nf-κb positively regulated mir-30b expression in ang ii-induced cardiomyocytes apoptosis, and bcl-2 was a direct target for mir-30b. 18941118_1 therefore, low expression of mir-34a in cll is associated with p53 inactivation but also chemotherapy-refractory disease, impaired dna damage response, and apoptosis resistance irrespective of 17p deletion/tp53 mutation. 22308110_1 nedd9 and cdk19 were identified as novel mir-18a target and were shown to be pro-proliferative genes, with rna interference of theirtranscripts decreasing proliferation in crc cells. 22308110_2 the 3' utr of nedd9 contains four potential binding sites for mir-18a, while the 3' utr of cdk19 contains three . 22308110_3 this supports the finding that nedd9 and cdk19 transcripts are direct target of mir-18a-mediated repression. 21146586_4 as shown , when a 251bp region of socs3 3'utr containing one mir-483-5p responsive element was cloned into a luciferase report vector. 21146586_5 these results suggest that mir-483-5p may carry out its functions by regulating the expression of the socs3 and tnf-α genes. 23671689_1 we show in this paper that ryhb is a direct regulator of the msrb gene that encodes the msrb enzyme. 23671689_2 ryhb down-regulates msrb transcripts along with hfq and rnasee proteins since mutations in the ryhb, fur, hfq, or rnasee-encoded genes resulted in iron-insensitive expression of msrb. 23671689_3 our results show that ryhb binds to two sequences within the short 59utr of msrb mrna as identified by reverse transcriptase and rnase and lead protection assays. 23671689_4 toeprinting analysis shows that ryhb pairing to msrb mrna prevents efficient ribosome binding and thereby inhibits translation initiation. 22811466_3 similar aip mrna and protein knockdown levels were obtained in sh-sy5y cells stably overexpressing mir-107 . 25160587_1 further studies revealed that mir-372 modulated the expression of phlpp2 by directly targeting its 3 0 -untranslated region and that mir-372 expression was inversely correlated with phlpp2 expression in glioma samples. 25160587_3 taken together, these results strongly suggest that phlpp2 is a direct target of mir-372. 25160587_4 these data demonstrated that mir-372 regulates cell proliferation and invasion by targeting phlpp2. 25700976_2 the expression of mir-185 had a negative correlation with tumor size, fuhrman grade, and tnm staging. 25700976_3 luciferase assay showed that vegfa was a direct target gene of mir-185. 25700976_4 the overexpression of mir-185 significantly inhibited cell proliferation and induced cell apoptosis by down-regulating vegfa expression in vhl-inactivated ccrcc cells. 23754433_1 in this report, we now show that three mirnas, let-7, mir-125, and mir-9, are key regulators of the early to late developmental transition in retinal progenitors: members of these three mirna families increase over the relevant developmental period in normal retinal progenitors; inhibiting the function of these mirnas produces changes in retinal development similar to dicer cko; overexpression of members of these three mirna families in dicer-cko retinas can rescue the phenotype, allowing their progression to late progenitors; overexpression of these mirnas can accelerate normal retinal development; microarray and computational analyses of dicer-cko retinal cells identified two potential targets of the late-progenitor mirnas: protogenin and lin28b; and overexpression of either lin28 or prtg can maintain the early progenitor state. 23754433_4 together, our data demonstrate that prtg is a target of let-7, mir-9, and mir-125. 24316060_1 in vitro, elevation of mir-146a by mir-146a mimics in drg neurons increased neuronal survival under high-glucose conditions. 24316060_2 downregulation and elevation of mir-146a in drg neurons, respectively, were inversely related to irak1 and traf6 levels. 24316060_3 treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented mir-146a expression and decreased levels of irak1 and traf6 in the drg neurons. in vitro, blockage of mir 146a in drg neurons abolished the effect of sildenafil on drg neuron protection and downregulation of irak1 and traf6 proteins under hyperglycemia. 22965997_1 klf4/5 is one of the targets of microrna-145 and is a known repressor of myocardin expression and a negative regulator of vsmc differentiation. 22965997_2 we evaluated the effects of microrna-145 lentiviral delivery on klf4 and myocardin expression and report that this form of microrna-145 treatment resulted in a reduction in klf4 levels with a concomitant increase in myocardin expression . 22965997_3 likewise, microrna-145 overexpression in hasmc elicited a decrease in klf4 expression and a parallel increase in myocardin expression . 22965997_4 the observation of a decline in klf4 levels and an elevation in myocardin expression is consistent with an effect of microrna-145 to promote a contractile phenotype of vsmc. 20133617_1 using unbiased genome-wide approaches in dlbcl, we discovered that the oncogenic microrna-155 directly target the bone morphogenetic protein -responsive transcriptional factor smad5. in addition, inhibiting mir-155 expression in relevant dlbcl cell lines elevated smad5 levels . 20133617_4 supporting the relevance of smad5 targeting by mir-155, dlbcls with stable smad5 knockdown became resistant to the cytostatic effects of bmp2/4 and tgf--beta1 and showed a defective induction of p21 . 26404322_1 the induction of mir-29b was accompanied with suppression of its downstream target dnmt3b in a dose-dependent manner. 26404322_2 as expected, similar and compatible results were observed in these two kinds of hcc cells transfected with mir-29b mimic , indicating that fucoidan increased mir-29b expression to negatively regulate dnmt3b in hcc cells. 26404322_3 furthermore, our results demonstrate that mir-29b directly represses dnmt3b expression by binding to its 3'-utr region, indicating the repression of dnmt3b by fucoidan in hcc cells is through mir-29b induction. 21924268_1 mir-1 directly target fn1 and downregulates its expression. 21924268_2 mir-1 can negatively regulate fn1 targeting its 3'utr and suppresses the growth and invasion of hep2 human laryngeal carcinoma cells. 21924268_4 we thus conclude that fn1 is a direct targetgene of mir-1. 21924268_5 these data show that fn1 is regulated by mir-1 at the mrna and protein levels. 21924268_6 in this study, we found that mir-1 can negatively regulate fn1 by targeting its 3- utr and suppresses the growth and invasion of hep2 human laryngeal carcinoma cells. 22079324_1 sirt1 expression in neurons was negatively regulated by mir-199a. 22079324_2 taken together, these results demonstrated that sirt1 is negatively regulated by mir-199a in neurons. 22079324_3 the level of sirt1 protein, a putative target of mir-199a and a known mediator of neuroprotective effect in brain ischemic tolerance, decreased significantly in hippocampal neurons by overexpression of mir-199a, while it increased with knockdown of mir-199a. 23299462_1 mir-107 directly target notch2 in glioblastoma cells. 23299462_2 as shown in fig.3b, c, the relative luciferase activities of the lenti-gfp-mir-107 groups transfected with notch2-3' utr-wt constructs were significantly decreased, compared to those transfected with notch2-3'utr-mut constructs, for both u87 and a172 cell lines, implying that notch2 is a direct target of mir-107. 23299462_3 these data suggest that notch2 was involved in glioma invasion and mir-107 may exerts its anti-invasive activity through notch2 signaling pathways. 21067862_1 sirt1, which was already demonstrated to be a targetgene of mir-34a , was overexpressed in the dld-1/5fu cells, as was shown in fig. 21067862_2 1a. the expression of sirt1 was clearly down-regulated after the transfection with mir-34a in both cell lines , whereas the mrna level of sirt1 was almost unchanged at 72 h in both cell lines . 21067862_3 not only sirt1 but also e2f3, which leads to cell growth and was also shown to be a targetgene of mir-34a , was significantly down-regulated in dld-1/5fu cells , as was shown in the parental dld-1 cells . 23001407_1 in addition, mir-17-5p inhibitor upregulated bim protein expression in a dose-dependent manner without changing the bim mrna level, and it increased the activity of a luciferase reporter construct containing the bim-3' untranslated region. 26070602_1 we observed robust repression in the luciferase activity of reporters carrying the 3- utr from csf1, gsk3a, akt2 and pras40 signifying that mir-184 expression can act via the 3- utr to destabilise the mrna of these targets . 26070602_2 these results suggest that mir-184 regulates the protein synthesis process by modulating expression of genes in addition to akt2, pras40 and gsk3a. 22018270_1 apc gene was identified as the direct and functional target of mir-27. 22018270_2 therefore, mir-27 may modulate wnt signaling by interacting with apc. the western blot analysis of ags cells treated with mir-27 demonstrated that mir-27 overexpression significantly decreased apc expression . 22018270_4 these data suggest that mir-27 promotes emt by activating the wnt/b-catenin pathway, and apc is the direct target of mir-27 in the wnt/b-catenin pathway. 22547075_1 induction of mir-21 may enable cancer cells to elude dna damage-induced apoptosis and enhance the metastatic potential of breast cancer cells through repressing expression of pten and pdcd4. 21872591_1 mir-21 is a putative regulator targeting rhob 3' utr. 21872591_2 sequence analysis indicate that mir-21 may complement nt 2309-2315 sequences of the rhob 3'-utr that is highly conserved across different species . 21872591_3 these data suggest that mir-21 expression is inversely correlated with rhob expression in human colorectal cancer cells, and it is possible that mir-21 negatively regulates rhob post-transcriptionally. taken together, these results indicate that mir-21 directly target rhob expression in colorectal cancer cells. 21872591_4 these results indicate that mir-21 can promote proliferation and inhibit apoptosis, effects that are associated with rhob downregulation. 26208701_1 mir-135a can target to thbs1 /thbs1 3'utr and contributes to the repression of thbs1/ thbs1. 26208701_2 our recent study demonstrated that prostaglandin 2 could repress thbs1 3'utr reporter activity through a mir-135a binding motif. 22470100_1 cyp1a1 is a target of mir-892a-mediated post-transcriptional repression. 22470100_2 luciferase assays revealed a sequence in the 3'-untranslated region of cyp1a1 that displayed a perfect match with mir-892a, and revealed that this sequence was a specific mir-892a targetsite. 22470100_3 these results suggest that mir-892a negatively regulates cyp1a1 function by inhibiting cell growth suppression in the presence of bap. 22470100_4 these results indicate that mir-892a is an effective post-transcriptional regulator of cyp1a1 mrna. 22470100_5 inversely, this downregulation was rescued by co-transfection with antago-mir-892a, indicating that mir-892a negatively regulates cyp1a1 expression post-transcriptionally by directly recognizing mre892a in the 3'-utr of cyp1a1. 20067763_2 to determine if up-regulation of mir-150 affects the expression of the endogenous target genes, we transfected sgc7901 cells with mir-150, a negative control or a vector control. 20067763_3 western blotting demonstrated that transfection of mir-150 in sgc7901 cells down-regulated egr2 expression while the negative control or vector only had little effect on endogenous expression of egr2 protein . 25915722_2 furthermore, mir-17-5p activated hscs through direct targeting of smad7. 25915722_3 these findings collectively suggest that smad7 is a direct target of mir-17-5p. 25915722_4 here, smad7 was predicted as a target of mir-17-5p, which was confirmed with the dual luciferase reporter experiment. 18408758_2 they describe for the first time the identification of the microrna hsa-mir-199a as a regulator of ikk-beta expression. 17381319_2 interaction of mir-122 with the 3'-noncoding region of the cellularmrna encoding the cationic amino acid transporter cat-1 resulted in the down-regulation of cat-1 protein abundance. 26201309_1 we have identified previously the mirnas let7b, mir16, mir181a, mir200b-3p, mir200b-5p, mir223 and mir483-5p that are predicted to target ro/ssa and la/ssb mrnas. 26201309_2 the msg levels of let7b, mir16, mir181a, mir223 and mir483-5p were correlated positively with ro52/trim21-mrna. 26201309_3 mir181a and mir200b-3p were correlated negatively with ro52/trim21 and ro60/trove2 mrnas in sgecs, respectively, whereas let7b, mir200b-5p and mir223 associated with la/ssb-mrna. 26201309_4 in pbmcs, let7b, mir16, mir181a and mir483-5p were correlated with ro52/trim21, whereas let7b, mir16 and mir181a were also associated with la/ssb-mrna expression. 22983447_3 in addition, overexpression of mir33b or mln2238 exposure negatively regulated oncogene pim-1 and blocked pim-1 wild-type, but not pim-1 mutant, luciferase activity. 22761789_1 here we show that dre-mir-2188 targets the 3'-untranslated region of nrp2a mrna and is implicated in proper intersegmental vessel development in vivo. 22761789_2 an in vivo gfp sensor assay based on a fusion between the gfp coding region and the nrp2a 3'utr confirms that mir-2188 binds to the 39utr of nrp2a and inhibits protein translation. 22761789_3 we demonstrate that mir-2188 targets nrp2a and affects intersegmental vessel development in zebrafish embryos. 22761789_4 the data show that mir-2188 regulates nrp2a, a vegf co-receptor, which is required for proper development of major isvs in zebrafish . 23000971_1 fig. 2. the ectopic expression of mir-350 can effectively inhibit the expression of endogenous p38 and jnk genes at the translational level. 23000971_4 these data strongly support the suggestion that p38 and jnk are direct targets of mir-350 . 25659925_1 downregulation ofmir-10b directly derepressed the expression of bcl2l11 as revealed by luciferase reporter assay. 19890474_1 lastly, analysing ship1 protein levels in b-cells isolated from wt and mir-155 transgenic mice, we found that ship1 is greatly reduced in mir-155 b-cells as compared to their wt counterparts , further supporting the notion that mir-155 post-transcriptionally regulates ship1 expression. 21793975_1 furthermore, the results of luciferase reporterassays suggested that mir-512-2 target the mycc gene. 21793975_2 after blocking the endogenous expression of mir-512-5p via a pgc-fu lentiviral vector, mir-512-5p expression was not detectable in hela or a549 cells, indicating that the knockdown was successful. 21793975_3 knockdown of mir-512-5p significantly upregulated the expression of mycc at both the mrna and protein levels in hela cells and in a549 cells . 21793975_4 figure 5. mir-512-2 overexpression reduces mycc protein in medulloblastoma cells. 21793975_5 deletion of the mir-512-2 gene was observed in one third of medulloblastomas, and was associated with overexpression of mycc. in vitro study further demonstrated that mir-512-2 target mycc expression in tumor cells. 25794773_1 luciferase assay was adopted to identify mtdh as a new direct target of mir-153. 25794773_2 overexpression of mir-153 significantly suppressed mtdh, as demonstrated by in vitro mtdh 3'-untranslated region luciferase report assay. 25794773_3 mtdh is a direct downstream target of mir-153 and is involved in the mir-153-induced suppression of the migration and invasion of breast cancer cells. 25794773_4 oncogene mtdh was specifically targeted by mir-153. 23991091_1 using mirna target prediction algorithms and the microarray transcriptomic profile of mir-155 2/2 livers, we identified and validated that nr1h3 as a direct mir-155 target gene that is potentially responsible for the liver phenotype of mir-155 2/2 mice. 23991091_2 lxra : a lipid pathway transcriptional regulator is a direct target of mir-155 in liver. in contrast, transfection with a mir-155 mimic in cd11b + cells from mir-155 2/2 livers resulted in downregulation of lxra. 26870180_2 mir-183 was found to be complementary to the 3'-utr of socs-6 . 26870180_4 all results indicated that socs-6 may be a target gene of mir-183-5p. 22521588_1 we found that mir-32 directly regulates the expression of slc45a3 by binding to the complementary sequence on the 3' utr of cldn11 and slc45a3. 22521588_2 these results attest that slc45a3 is a myelin-enriched protein regulated by mir-32. 22521588_3 furthermore, as both processes are crucial for oligodendrocyte development and function, this also suggests that slc45a3 may be one of the main downstream target of mir-32. 26239517_1 furthermore, low-density lipoprotein receptor-related protein 6 , a regulator of the wnt/ -beta -catenin signaling cascade, was identified as a crucial target gene of mir-126. 26239517_2 we identified low-density lipoprotein receptor-related protein 6 as a direct target of mir-126 and showed that overexpression of mir-126 in ptc cells inhibited cell proliferation, migration and invasion and suppressed tumor growth in a nude mouse model. 26239517_3 luciferase assay further revealed that tpc-1 cells transfected with mir-126 mimic repressed wild-type lrp6-3'utr reporter activity , while mir-126 mimic had no inhibition effect on the mutant lrp6-3'utr reporter activity , indicting the direct regulation of mir-126 in the 3'utr of lrp6 mrna. 26239517_4 these data indicated that mir-126 suppressed ptc cell tumorigenicity in vivo by targeting lrp6. 22684006_2 microrna-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting bmpr2. 22684006_3 taken together, these results revealed that mir-100 could regulate bmpr2 protein expression through a partially complementary binding site in the 3'-utr of bmpr2. 22684006_4 from a sidewise approach, we demonstrated that deletion of the targetcould block the effect the mir-100 inhibition, further indicating that mir-100 regulated the osteogenesis of hascs through bmpr2. 22615492_1 these data indicate that exogenous and endogenous mir206 can target pk1a through the mir206 binding site in its coding sequence. 26068649_1 phosphatase and tensin homolog was confirmed to be directly bound by mir-26b by dual-luciferase reporter assay, and was down-regulated in mir-26b over-expressing nsclc cells. 26068649_2 finally, when pten was up-regulated in nsclc cells, it reversed the effects of mir-2b over-expression on nsclc migration and cisplatin chemosensitivity. 26272918_1 luciferase assays and transfections in human foetal myoblasts showed that twist-1 is a direct target of mir-206 and that through this pathway muscle cell differentiation is promoted. 26272918_2 our results show that mir-206 is a negative regulator of twist-1 and promotes muscle cell differentiation. 26272918_3 these results support the findings of earlier experiments that twist-1 is a target for mir-206 in order to induce muscle cell differentiation. 21994419_1 overexpression of mir-148a in gastric cancer cells could reduce the mrna and protein levels of rock1, whereas mir-148a silencing significantly increased rock1 expression. 21994419_2 luciferase assays confirmed that mir-148a could directly bind to the 2 sites of 3' untranslated region of rock1. 19826040_2 unbiased microarray analysis combined with bioinformatics identified cell cycle regulator cdc25a as a mir-21 target. 19826040_3 mir-21 suppressed cdc25a expression through a defined sequence in its 3'-untranslated region. 19826040_4 we found that mir-21 is induced by serum starvation and dna damage, negatively regulates g -s transition, and participates in dna damage-induced g -m checkpoint through down-regulation of cdc25a. in contrast, mir-21 deficiency did not affect apoptosis induced by a variety of commonly used anticancer agents or cell proliferation under normal cell culture conditions. 19826040_6 our data show a role of mir-21 in modulating cell cycle progression following stress, providing a novel mechanism of cdc25a regulation and a potential explanation of mir-21 in tumorigenesis. 21469086_1 mir-21 targets directly the expression of programmed cell death 4 and overexpression of mir-21 in cells harboring the 3'utr of pdcd4 resulted in reduced transcription and pdcd4 protein expression 26603571_1 our results showed that lactb was a potential target of mir-125b-5p based on bioinformatics analyses and dual-luciferase reporter assays. 26603571_2 moreover, mir-125b-5p directly inhibited lactb protein and mrna expression by targeting lactb 3 ' utr. 26603571_4 moreover, mir-125b-5p directly inhibited lactb protein and mrna expression by targeting lactb 3 ' utr. to investigate the precise association and underlying mechanism between mir-125b-5p and lactb, the present study confirmed, using a luciferase reporter assay, that mir-125b-5p directly targeted the lactb gene through binding to a specific complementary site within its 3 ' utr. 25706919_2 dual-luciferase reporter assay recognized pdrg1 as direct downstream target gene of mir-214 21466664_1 luciferase reporter assays demonstrated that mir-155 interacted with ski 3'utr and impaired gene expression. 21466664_2 figure 2. mir-155 interacts with the 3'utr of ski mrna. 21466664_3 we concluded that in gl-mel and sk-mel-28 cell lines, ski mrna retains the 3'utr region encompassing mir-155-binding site. 21466664_4 moreover, in these cells, a 482-bp region of ski 3' utr encompassing mir-155-binding site was amplified by rt-pcr and subjected to direct sequencing. 21466664_5 no sequence variations were detected . the results illustrated in figure 4c show that the transient transfection with anti-mir-155 up-regulated ski in targetcells, while the control rna oligonucleotide was ineffective. 21466664_6 in conclusion, our study clearly demonstrates that ski is a target of mir-155 and provides evidence that mir-155 down-regulation can be involved in ski overexpression in melanoma cells. 20067797_1 we then showed that mir-29a negatively regulated collagen iv by directly targeting the 3'utrs of col4a1 and col4a2. 20067797_3 4b, compared with the mirna negative mimic, transfection of the mir-29a mimic decreased the luciferase activity of col4a1-site1, col4a1-site2 and col4a2 by 40.5%, 41.9% and 47.4%, whereas the mutant sequence restored levels to 66.4%, 64.0% and 77.8%, respectively. 20067797_4 taken together, our data demonstrate that mir-29a can directly regulate col4a1 and col4a2 through their 3'-utrs. 25798837_1 figure 5h shows that co-transfection of upa sirna with anti-mir-193b abrogated the increase in migration owing to mir-193b inhibition, suggesting that upa is a mediator of the effects of mir-193b downregulation. 25798837_2 figure 5. mir-193b inhibits metastatic colonization of ovarian cancer cells through its target, upa. 26729612_1 ectopic expression of mir-33b in hgc-27 and mgc-803 cells inhibited cell proliferation, migration and invasion, which might be due to mir-33b targeting oncogene c-myc. 26729612_2 further investigation indicated that the tumor suppressive roles of mir-33b might be through directly repressing c-myc. 26729612_3 after alignment, we truly found the binding site of mir-33b in the 3- utr of c-myc mrna . 26729612_4 these results indicated that mir-33b might inhibit tumor migration, invasion and proliferation by directly targeting oncogene c-myc in gc. 22685420_1 to confirm this, we utilized a luceriferase reporter assay to determine the effect of mir-93 on the expression of the stem cell regulatory genes akt3, sox4 and stat3 selected from the expression profiling data. 22685420_3 furthermore, knockdown of stat3 or sox4 but not akt3 decreases the proportion of aldh+sum159 cells suggesting these genes play a role in the regulation of csc self-renewal . 21925125_1 mir-139 significantly suppressed the expression of a luciferase reporter gene fused to 3- untranslated region of cxcr4 , which could be reversed by further introduction of a 2- -o-methyl antisense oligonucleotide targeted to mir-139 . 21925125_2 although antisense oligonucleotides targeting mir-139 partially restored cxcr4 expression in her2 knockdown cells , synthetic mir-139 mimics significantly inhibited the cxcr4 mrna levels regardless of her2 and cd44 expressions . 21925125_3 thus, cd44 synergizes with her2 to stabilize cxcr4 mrna via inducing an intense down-regulation of mir-139 that targets cxcr4. 22684561_1 bioinformatics and luciferase assay were performed to predict and analyze the binding sites between mirna-34a and notch1. 22684561_3 binding of mir-34a to notch1 3'utr. 22684561_4 luciferase assays showed that mir-34a significantly down-regulated the relative luciferase activities in 253j and j82 cells , suggesting that mir-34a binds notch1 3'utr. 19591824_1 we additionally show that dleu2 negatively regulates the g1 cyclins e1 and d1 through mir-15a/mir-16-1 and provide evidence that these oncoproteins are subject to mir-15a/mir-16-1-mediated repression under normal conditions. 24421392_1 mir-34a inhibition and sirt1 overexpression significantly rescued targeting of the mir-34a pathway and apoptosis by dca. 26246194_1 mir-29 is predicted to target the ahr 3- utr at a site that is highly conserved between human and mouse. in the presence of the mir-29a mimic, relative levels of luciferase activity were reduced by more than 50% . 26246194_3 these data support the model that inhibition of mir-29 in vivo leads to the loss of mir-29-mediated repression of ahr and thereby promotes the anti-lipogenic activity of ahr. 23747308_1 these data indicated that mir-150 directly targeted p53. 23747308_2 these results indicated that p53 was the functional target of mir-150 in a549 cells. 23747308_3 these results indicated that upregulation of mir-150 increased the cell proliferation that was normally suppressed by p53 in nsclc cells. 23747308_5 mir-150 specifically targeted p53 in the nsclc cell line a549. 23747308_6 by using luciferase reporter system, we verified mir-150 directly target p53 transcript at its 3'utr and inhibit its translation. 24418124_1 our results also indicated that upregulation of mir-16 promoted apoptosis by suppressing bcl2 expression. 21625387_1 we demonstrate, by means of luciferase assays, that mir-103 and mir-107 are able to directly interact with the cdk5r1 3'-utr, in correspondence of a specific targetsite. 21625387_2 taken together, these results suggest that mir-103 and mir-107 can affect cdk5r1 expression in sk-n-be cells. 21625387_3 these results confirm that mir-107 directly regulates cdk5r1 expression at translational level. 21625387_4 the co-transfection in sk-n-be of this construct with pre-mir-103 or pre-mir-107 led to a reduction of luciferase activity , in comparison to the luciferase activity measured in the same cells transfected only with pgl4.71p-utr, 26840028_1 in this study, we found that mirna mir-1827 is a novel mirna that targets mdm2 through binding to the 3'-utr of mdm2 mrna. 26840028_2 mir-1827 negatively regulates mdm2, which in turn increases p53 protein levels to increase transcriptional activity of p53 and enhance p53-mediated stress responses, including apoptosis and senescence. 26840028_3 collectively, these results demonstrate that mir-1827 is a bona fide mirna targeting mdm2. 26840028_4 these data strongly suggest that mir-1827 directly binds to mdm2 mrna in vivo. 26840028_5 these results strongly suggest that mir-1827 targets mdm2 through direct binding to the four binding sites in mdm2 3'-utr. 26824451_1 in addition, we found that the tob1 3' untranslated region is a direct target of mir-218. 26824451_2 fig. 5. tob1 3'-utr is a direct target of mir-218. 26824451_3 furthermore, tob1 protein was significantly downregulated by mir-218 mimic and upregulated by mir-218 inhibitor. 23892108_1 using 3'-utr luciferase reporter gene assay, we found that mir-92b directly affected smad3 expression in gbm cells by targeting the 3- -untranslated region. 23892108_2 taken together, these findings demonstrated that smad3 was a direct target of mir-92b in gbm cells. 23892108_3 this study confirmed for the first time that mir-92b directly regulated smad3 expression at protein levels in solid cancer by targeting on the 3- -untranslated region. 21658607_1 here we show that mir-125a targeting psd-95 mrna allows reversible inhibition of translation and regulation by gp1 mglur signaling. 21658607_2 these data on the endogenous psd-95 and luciferase reporter with psd-95 3'-utr suggest that antimir-125a relieved the translational inhibition imposed on the psd-95 3'-utr containing an intact binding site for mir-125a. 21658607_3 this suggests that a single mir125a targetsite may be largely responsible for ago2-mediated translational regulation in the context of the psd-95 3'-utr. 21658607_4 these results indicate mir-125a specifically target the 3'-utr of psd-95 mrna and is essential for mglur-mediated translation in neurons. 21658607_5 this data suggest that the excessive spine density and spine branching observed by antagonization of mir-125a is mediated by the increased synthesis of psd-95. 21658607_6 these data indicate the critical role of s499 of fmrp in mediating the inhibition and mglur mediated activation psd-95 mrna translation involving mir-125a. 26554866_1 taken together, these results indicate that the tumor-suppressor role of mir-506 is mediated by targeting stat3. 26554866_2 figure 4. mir-506 targets stat3 and inhibits its expression in glioma cells. 26554866_3 these results indicate that mir-506 suppresses glioma growth in vivo by targeting stat3. 26473472_1 we predicted that mir-378g may target shp-1 3'utr region by targetscanhuman. 26473472_2 to find out whether the 3'utr of shp-1 mrna is a target of mir-378g in npc cells, the natural sequence of shp-1 3'utr or the mutant sequence were connected into a luciferase reporter vector. 26473472_3 mir-378g mimics inhibited shp-1 expression significantly . 26473472_4 taken together, all these results strongly indicated that shp-1 was a target of mir-378g in npc cells. 22673513_1 here, we describe that mir-26, an lxr-suppressed mirna, inhibits the expression of the atp-binding cassette transporter a1 and adp-ribosylation factor-like 7 , two lxr target genes which play critical roles in cholesterol efflux. 22673513_2 here, we report that mir-26, which is suppressed after lxr activation, could target two important regulators of the lxr-dependent cholesterol pathway thus control cholesterol metabolism. in conclusion, the luciferase reporter system proved that mir-26 could target abca1 and arl7 via the mir-26 binding sites located in their 3'-utrs. 26821743_1 we found negative correlations between the expression level of let-7e and il-10 messengerrna and between the expression level of let-7e and proportion of il-10+ cells in stimulated pbmcs from healthy volunteers . 25426560_2 we conclude that mir-24-3p regulates autophagy by targeting atg4a. 25426560_3 furthermore, to our knowledge, our study is the first to confirm atg4a as a direct functional target of mir-24-3p in sclc. 25426560_4 these results demonstrated that mir-24-3p directly targeted atg4a to repressively mediate autophagy induction. 22453125_1 furthermore, luciferase reporter assay demonstrated that mir-328 directly target abcg2 and mmp16 and affects the levels of mrna and protein expression in sp cells. 22453125_2 taken together, these data indicate that mir-328 downregulation may contribute to the overexpression of abcg2 and mmp16 in sp cells. 22453125_3 our results confirmed that mir-328 directly target abcg2, which is in agreement with recent studies , supporting that mir-328 affect the number of sp cells and drug resistant in part through this pathway. 22453125_4 in addition to abcg2, we found that mmp16 is also a direct target of mir-328. 25412960_1 to further demonstrate the effect of mir-200a on the reversal of emt signatures in lcscs, we transfected mir-200a mimics or non-specific control mirna mimic into lcscs. 25412960_3 data showed that overexpression of mir-200a in lcscs resulted in the upregulation of epithelial marker e-cadherin and downregulation of mesenchymal marker zeb2, n-cadherin, and vimentin at mrna and protein level . 26846382_1 furthermore, sprouty 2 was identified as a novel target of mir- 27b in hcc hepg2 cells, and the protein expression levels of spry2 were negatively regulated by mir- 27b in hepg2 cells 20668064_1 ectopic mir-16 had a pronounced suppression against the induction of wip1 proteins, whereas antagomir-16 promoted the expression of wip1 . 20668064_2 transfection of antagomir-16 increased the luciferase activity by ~50% for the wip1 3'-utr reporter construct. 20668064_3 deletion of six nucleotides of seed sequence almost completely abolished the effects of pre-mir-16 and antagomir-16 on the luciferase transcripts with the wip1 3'-utr, suggesting that the wip1 gene is an authentic target of mir-16 in vivo . 20668064_4 these results suggest that mir-16 is an important regulator for wip1 induction in the early stage of dna damage response. 20668064_5 our results indicated that mir-16 sensitizes mcf-7 cells to the treatment of doxorubicin by inhibiting wip1. 20668064_6 restoration of wip1 in the mir-16 overexpressed cells remarkably reversed the inhibitory effect of mir-16 on blocking mammosphere formation in culture, suggesting that wip1 is a primary target of mir-16 in the regulation of mammary tumor stem cells . 15843373_4 hasnt expression reduced both has2 mrna levels and ha biosynthesis. 22235338_1 exogenous mir-211 directly binds the 3'-untranslated region of chd5 mrna, resulting in a 50% decrease in chd5 protein level in hct-116 cells. 22235338_2 our results demonstrate that chd5 is a direct target of mir-211 regulation. in addition, chd5 was confirmed as a direct target of mir-211 by a luciferase reporter assay. 22235338_3 fluorescence activity decreased over 90% after 293t cells were co-transfected with the mir-211 expression vector and 3'-utr of chd5 mrna luciferase reporter vector compared to the 3'-utr of chd5 luciferase reporter vector alone . 22235338_4 our results demonstrate that enforced expression of mir-211 in the colorectal cancer cell line hct-116 increased the malignant phenotype of the cells by directly downregulating the expression of chd5 and may be by modulating p53-related pathways. 22235338_5 our study provides a better understanding of regulatory capacity of the mir-211 in promoting colorectal tumorigenesis by targeting chd5 expression. 26181633_1 high glucose significantly increased klf4 protein expression at 6 h and overexpression of wt mir-145 significantly attenuated the klf4 protein expression induced by high glucose. 26181633_2 to investigate whether klf4 is a direct target of mir-145, we performed a luciferase assay to measure klf4 promoter activity,significantly increased klf4 promoter activity as compared with control cells. 26181633_4 when the conserved site of mir-145 in the promoter area of klf4 was mutated, the increased promoter activity induced by high glucose and ang ii was abolished. 26181633_5 luciferase assay also showed that mir-145 is able to bind klf4 and myocardin 3'-utr and induced the opposite expression. 26181633_6 overexpression of mir-145 under high glucose stimulation attenuated klf4- 3- utr luciferase activity and increased myocardin- 3- utr luciferase activity at 4 h. 26803387_1 pearson's correlation coefficient test showed a negative correlation between mir-92 and erb1 expression, based on analysis of ihc staining results .the 26803387_2 result suggested the possibility that down-regulation of erb1 in uterosacral ligaments of pop patients- correlates with upregulation of mir-92. 26803387_3 results from our correlation analysis confirmed that mir-92 expression was negatively correlated with erb1 expression in pop patients, suggesting that mir-92 could potentially target erb1 at mrna level to negatively regulate its expression. 26803387_4 erb1 has been identified as a target of mir-92 in one study. 25753120_1 transfection studies confirmed that des-mediated downregulation of mir-18b and mir-23a led to increased fasl and fas expression. 25753120_2 these data demonstrated that prenatal des exposure can cause alterations in mirs, leading to changes in the gene expression, specifically, mir-mediated increased expression in fasl and fas causing apoptosis and thymic atrophy. 22219591_1 to confirm our microarray and quantitative rt-pcr data, we also performed mirna-specific in situ hybridization analyses on ff-pe tissues and identified hmga2 as a promising biomarker of bm transformation on immunohistochemical analysis. 19582148_1 in this report, we demonstrate that fog-2 expression is controlled at the translational level by microrna-130a. 19582148_2 these observations strongly suggest that mir-130a is acting through the a site of the fog-2 3'-utr to mediate translational repression. 19582148_3 taken together with the loss of function experiments described above, these results demonstrate that mir-130a target the fog-2 3- utr to inhibit mrna translation. 19582148_4 these results support the hypothesis that translation of fog-2 mrna is regulated by mir-130a in cardiomyocytes in vivo. 26801178_1 the luciferase assay showed that in vitro, the mir-310s could target the rab23, dhr96, and ttk transcripts via their 3'utrs . 26801178_2 these data demonstrate that the mir-310s act to fine tune the expression of the nutrition-dependent genes rab23, dhr96, and ttk; furthermore, the mir-310s regulate ttk only upon dietary restriction. 23095762_1 targeting of the 3'-untranslated region of pcaf mrna by mir-17-5p caused translational suppression and rna degradation, and, consequently, modulation of ar transcriptional activity in pca cells. in this study, we investigated the expression of pcaf in pca cells, its targeting by mir-17-5p, and its potential effects on ar transcriptional activity. 23095762_2 the data demonstrate that pcaf is a targetfor mir-17-5p in pca cells. 23095762_3 downregulation of mir-17-5p causes overexpression of pcaf in human pca cells, promoting ar transcriptional activity and pca cell growth. 23095762_4 significant complementarity between pcaf 3'-utr and mir-17-5p has been identified in previous studies . 23095762_5 to correlate expression of mir-17-5p to pcaf upregulation in pca cells, we generated a luciferase construct that contains the potential binding sequence of pcaf 3'-utr to mir-17-5p . 25587068_1 uponinductionin vitro, mir-687 repressed the expression of phosphatase and tensin homolog and facilitated cell cycle progression and apoptosis. 25587068_2 similarly, in a renal tubular cell line , mir-687 expression increased during hypoxia and anti-mir-687 transfection suppressed hypoxia-induced decrease in pten expression , further supporting a role of mir-687 in pten repression under hypoxic conditions. 25587068_3 our current work has further identified that mir-687 can directly target pten for downregulation under conditions of hypoxia and ischemia in kidney cells and tissues. 20962090_1 mdv1-mir-m3 suppressed cisplatin-induced apoptosis by directly downregulating expression at the protein but not the mrna level of smad2, a critical component in the transforming growth factor beta signal pathway. 21984808_1 by transfecting keratinocytes with a mir-21 mimic, we identified the existence of two groups of the bmp target genes, which are differentially regulated by mir-21. 21984808_2 mir-21 differentially regulates expression of the bmp target genes and modulates effects of bmp-4 on cell proliferation and migration.the 24578127_1 overexpression of mir-29a attenuated the promotion of hdac4 signaling, nephrin ubiquitination, and urinary nephrin excretion associated with diabetes and restored nephrin acetylation. 21827835_1 these results indicate that let-7e may protect pc12 cells against apoptosis following a/r injury by negatively regulating the expression of casp3. 26808577_1 in addition, mir-206 inhibited ccrcc cell proliferation through inducing cell cycle arrest by directly targeting cell cycle related gene cdk4, cdk9 and ccnd1. 26808577_2 hence, the above findings confirmed that cdk4, cdk9 and ccnd1 were indeed novel direct targets of mir-206 in ccrcc cells. in summary, cdk4, cdk9 and ccnd1 are upregulated in ccrcc tumors and their negative regulation by mir-206 is clinically relevant in the context of ccrcc. 16969504_1 mir-143 and mir-145 expression levels were extremely reduced in the colon cancer cells. 26311740_1 mir-21 regulates pten expression and akt activation in hcc cells. 26311740_2 these results indicate that mir-21 overexpression in sorafenib-resistant hcc cells is accompanied by the elevated targeting function of mir-21. 26311740_3 among the mir-21 targets, pten is a well characterized tumor-suppressing phosphatase that inhibits akt activation. 18922928_2 mechanism may be due to altered regulation of the kras oncogene and possibly cellular let-7 levels as well. 19509287_1 in silico analysis predicted that mir-105 had complementarity for tlr-2 mrna, and the luciferase reporter assay verified this. 19509287_2 this analysis revealed a generalized, strong inverse correlation between tlr2 protein and mir-105 gene expression . 19509287_3 this confirmed that mir-105 up-regulation suppressed tlr-2 protein expression on the cell surface. 19509287_4 we may conclude that modulation of tlr-2 expression by mir-105 occurs through binding to the 3'-utr of tlr-2 mrna, thus inhibiting tlr-2 translation 23554959_1 luciferase reporter assays demonstrated that mir-574-3p decreased the relative luciferase activities of rac1, egfr and ep300 except for other four genes. 23554959_2 mutation of the putative mir-574-3p binding sites in these 3'-utrs decreased the response to mir-574-3p indicating that mir-574-3p binds directly to the 3'-utrs of rac1, egfr and ep300. 25889022_1 through depleting mir-125b in t cells using a mir-125b inhibitor, the decrease of foxp3 expression induced by glps was abolished , suggesting that the inhibition of tregs by glps might act through increasing mir-125b expression. 25889022_4 as shown in figure 4f, glps treatment significantly down-regulated notch1 expression, which was restored by the mir-125b inhibitor. 25889022_5 these data indicate that glps could decrease foxp3 levels by mir-125b down-regulation of notch1 expression. 23878390_1 inhibition of mir-329 in huvecs or hmecs resulted in increased expression of cd146 at both the protein and mrna levels , suggesting that endogenous mir-329 indeed participates in the regulation of endothelial cd146. 23878390_2 together, these data suggest that mir-329 targets cd146 mrna directly, namely through binding to the 3'-utr sites 1 and 4. these experiments further support the direct negative effect of endogenous mir-329 on the cd146 3- utr via binding sites 1 and 4. fig 4 mir-329 inhibits angiogenic signaling by targeting cd146. 23878390_3 taking these results together, we could show that when overexpressed above physiological levels, mir-329 can suppress the expression of effector genes that promote angiogenesis, predominantly through targeting of cd146. 23878390_4 these findings indicated that mir-329 inhibited endothelial cell function mainly through targeting of cd146. 23872151_2 our analysis revealed that rock1was a potential target of mir-340 based on putative target sequences at position 1317-1323 of the rock1 3' utr. 23872151_3 taken together, these findings indicated that rock1 is a functionally important target of mir-340 that is in-volved in the proliferation, migration and invasion of os cells. 21980462_1 mir-18a suppresses atm expression by targeting 3'-utr of atm. 21980462_3 however, point mutations in the tentative mir-18a-binding seed region in the atm 3'-utr abrogated the suppressive effect of atm expression mediated by mir-18a . 21980462_4 thus our results demonstrate that atm is a bona fide target of mir-18a. 21980462_5 collectively, these results further supported the notion that atm is the target of mir-18a. 21980462_6 these results suggest that atm repression is essential for the role of mir-18a in hrr and cell radiation sensitivity. 21980462_7 taken together, our results suggest that upregulation of mir18a in nbecs is sufficient to impair atm activation and hrr events upon ir treatment. 21980462_8 these results further supported the hypothesis that mir-18a impaired dna repair through the downregulation of atm. 18950466_3 as expected, the mutations of the complementary bases abolished the interaction between mir155 and ets-1 3'-utr. 22414602_1 three internet-based algorithms identified mir-96 to potentially bind with the alk 3'-untranslated region. 22414602_2 transfection of the cell lines with mir-96 decreased levels of the different forms of alk protein, without significant effects on alk mrna, indicating that decreases in mir-96 could represent a mechanism underlying the aberrant expression of alk in cancer cells. 26823698_1 implying that mir-377 could directly bind to aeg-1 3'-utr; in other words, aeg-1 is a target gene of mir-377. 23349832_1 the mechanisms underlying the effects of mir-22 included a reduction in caspase activation, consistent with mir-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 and tumor protein p53-inducible nuclear protein 1 . 26316588_1 the database predicted mir-185 and mir-182 as potential mirnas to target rage. 26316588_2 the results showed mir-185 inhibited the expression of the transcript containing the wild type 3'-utr of rage significantly compared to the negative control. 26316588_3 these data demonstrated a speci铿乧 translational inhibitory effect of mir-185 on the 3'-utr of rage through direct interaction. 26316588_4 the above data indicated expression of endogenous rage is negatively regulated, at least in part,by mir-185. 23296701_1 fgfr1 is a targetgene of mir-133b. 23296701_2 these findings suggest that mir-133b regulates fgfr1 expression at post-transcriptional level. 23296701_4 our results together indicated that fgfr1 is upregulated in gc and inversely correlated with mir-133b in the gc tissues. 23296701_5 we also demonstrated that mir-133b regulated fgfr1 expression at the posttranscriptional level, as the mrna level of fgfr1 was not affected. 17629449_1 bdnf and antibdnf transcripts form dsrna duplexes in the brain in vivo, suggesting an important role for antibdnf in regulating bdnf expression in human. 17629449_3 we named the gene and transcripts transcribed from the opposite strand of bdnf as antibdnf . 19881956_5 we report that egfr signaling leads to transcriptional repression of the mirna mir-125a through the ets family transcription factor pea3. overexpression of mir-125a induces conversion of highly invasive ovarian cancer cells from a mesenchymal to an epithelial morphology, suggesting mir-125a is a negative regulator of emt. 19881956_6 we identify at-rich interactive domain 3b as a target of mir-125a and demonstrate that arid3b is overexpressed in human ovarian cancer. 26386386_1 the high abcg2 expression in the tumor is associated with the concomitant overexpression of the mrna binding protein hur but a low expression of mir-519c because mir-519c is known to target both abcg2 and hur. 26386386_2 further investigation in crc cell lines revealed that the abcg2 overexpression was caused by an interplay between mir-519c, hur and the length of the 3' untranslated region of abcg2. 26386386_3 fig. 3. mir-519c regulates both hur and abcg2 expression in s1m1 80 cells. 26386386_4 fig. 4. both mir-519c and hur can independently regulate abcg2 expression and transport activity in s1 and s1m1 80 cells. 24565984_1 over expression of mir-138 in hnscc lines showed down regulation of rhoc, as well as a decrease in cell motility, invasion colony and stress fiber formation. 24565984_2 interestingly, mir-138 has been confirmed to regulate rhoc expression in oral squamous cell carcinoma by targeting 3'-utr of rhoc mrna . 24565984_3 this novel finding, reported for the first time in this study, demonstrates the role of mir-138 in the regulation of rhoc expression in both cell lines and primary hnscc tumors. 26801503_1 data from reporter assays showed that mir-455 directly binds to 3'-utr of zeb1 and suppresses the endogenous level of zeb1 protein expression. 26801503_2 we also identified a target of mir-455, zeb1 , and demonstrated that mir-455 down-regulated its expression in lung cancer cells. 26801503_3 our results showed that the protein level of zeb1 was declined in the mir-455 transfected cell lines compared to the negative controls , suggesting that mir-455 directly bind to zeb1. 26801503_4 furthermore, we provided evidence that overexpression of mir-455 significantly suppressed nsclc cell proliferation, migration and invasion by targeting zeb1. 25153722_2 validated ezh2, mcl-1 and fos as direct targets of mir-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microrna-101 function. 23071313_1 this analysis predicted the transcriptional regulators nfkbiz, bcl6, and smad1 as the most highly probable mir-187 target genes . 23071313_2 furthermore, additional observations indirectly supported the prediction of nfkbiz as one of the most likely mir-187 targetgenes. 23071313_3 deletion of the upstream 1,111 bp of the nfkbiz 3'-utr , containing an active mir-124 seed region , did not modify the mir-187-mediated inhibition of luciferase activity, which instead was reversed by deletion of 5 bp in the mir-187 seed region in the nfkbiz 3'-utr , demonstrating the specificity of mir-187: nfkbiz 3'-utr interaction. 23071313_4 collectively, these data clearly demonstrate that mir-187 posttranscriptionally regulates nfkbiz and tnfa gene expression by driving the physical association of igammabζ and tnf-alpha mrnas to the risc complex. 25482440_1 furthermore, target micrornas of acpp such as mir-192 and mir-215 regulated acpp gene expression at the post-transcriptional levels by binding to specific sites within its 3 ' -utr. 25482440_2 also, our results indicated that expression of acpp is regulated by specific target mirnas including mir-192 and mir-215 at the post-transcriptional level through binding directly to their target sequences in the 3 0 -utr of the acpp gene. 25482440_3 results of the present study indicated that the 3 ' -utr of rat acpp gene contains mir-192 and mir-215 binding sites, and the two mirnas attenuate intensity of gfp-acpp expression in cells by directly binding to the their specific sites at the 3 0 -utr. 24260067_1 subsequently, bcl-2 was identified as a potential mir-449a target by bioinformatics analysis. 24260067_2 it was also shown that bcl-2 was negatively regulated by mir-449a at the post-transcriptional level, via a specific target site within the 3'-untranslated region , by luciferase reporter assay. 26574780_1 in summary, our findings indicate that meg3 function as a tumor suppressor by regulating mir-21-5p, resulting in the inhibition of tumor growth in cervical cancer. 26574780_2 taken together, our date suggested that meg3 may function as tumor suppressing lncrna in cervical cancer cells at least in part by downregulating mir-21-5p. 26574780_3 in summary, we suggest that mir-21-5p could rescue both the effect on cell proliferation and apoptosis induced by meg3 in hela and caski cells. 26574780_4 this finding indicated that the meg3 may negative regulated the expression of mir-21-5p but they may not form a reciprocal repression feedback loop. 25881561_1 revealed that s1pr1 is a predicted target gene of mir-17- 92 with five out of six members of the cluster targeting it. 25881561_2 we next determined if s1pr1 was indeed targeted by mir-17- 92. the 3'-utr of s1pr1 contains four predicted binding sites with mir-19a and mir-19b targeting two sites and mir-17, mir-20a and mir-92a each targeting one site . 25881561_3 a luciferase reporter construct with full-length s1pr1 3'-utr dna fragment was cloned downstream of firefly luciferase coding sequence and transfected into hek293 cells together with either the whole mir-17- 92 cluster or individual relevant mirnas. 25881561_4 thus, our results suggest that s1pr1 is a bona fide target of mir-17- 92, with five out of six members directly targeting its 3'-utr at four different sites. 22732186_1 ionizing radiation decreased mir-302 levels, which was associated with an increase in its targetmrna levels, arid4a and ccl5. 22732186_2 results from a q-rt-pcr and dual luciferase-3'-utr reporter assays identified arid4a and ccl5 as target for mir-302. 22732186_3 mir-302 regulates arid4a and ccl5 mrna levels through targetsequence in the 3'-utrs. 22732186_4 we found that both arid4a and ccl5 are putative target of mir-302 and involved in cell proliferation. 22732186_5 arid4a contained 2 highly conserved targetsites for mir-302 and ccl5 contained 1 targetsite for mir-302 . 22732186_6 these results demonstrate in vivo interactions between mir-302 and its targetsequences in arid4a and ccl5 mrnas. 22732186_7 because radiation is well known to generate ros, these results also suggest that the interaction between mir-302 and its targetsequences in arid4a and ccl5 could be sensitive to changes in cellular ros levels. 22732186_8 these results demonstrate ros sensitivity of mir-302 regulation of arid4a and ccl5 mrna levels. 22732186_9 these results suggest mir-302 regulates transitions between quiescence and proliferation presumably by ros-sensitive regulation of arid4a and ccl5 mrna levels. 26432843_1 we determined fibroblast growth factor receptor substrate 2 mrna to be a target of mir-145, both in an in vivo model and in h9c2 cells. in conclusion, post-mi treatment with mir-145 protected the heart through the induction of cardiomyocyte autophagy by targeting fibroblast growth factor receptor substrate 2. these results demonstrated that mir-145 directly targeted frs2. 22119803_1 moreover, tgfbr2, pten, pdcd4, and tap63 were identified as target of mir-21 in hacat cells. 22119803_2 based on these data, endogenous tgfbr2 protein expression was indeed regulated by mir-21 and this kind regulation may partially explains the bypassing of cytostatic response to tgf-1 induced by mir-21. 22119803_3 compared to pre-mir control, both the levels of tgfbr2 protein and mrna were significantly down-regulated by mir-21 precursor . 22119803_5 7a, protein levels of pdcd4, pten, and tap63 were downregulated to varying degrees by pre-mir-21 but not in pre-mir control-transfected cells . 22119803_6 these data suggest that pdcd4, pten, and tap63 are target of mir-21 in hacat cells. 22119803_7 these data indicate two other mir-21 targetgenes, pten and tap63, are also involved in mir-21-mediatedresistance to tgf-1 cytostatic response except tgfbr2. 22119803_9 6. tgfbr2 is an important functional target of mir-21. 25858147_1 let7 regulates tumor initiation of oscc through targeting the 3'utr of arid3b and hmga2. in our oscc model,we also find that let7 supressed hmga2 expression through binding on it's 3'utr 26045994_1 mir-222 targets vgll4 in gc cells. 26045994_2 these results strongly suggest mir-222 negatively regulates vgll4 expression via direct binding to putative binding site in the vgll4 3'-utr region. 26700765_1 mechanistically, we found that mir-27a directly targeted sialic acid-binding ig-like lectin 1 and e3 ubiquitin ligase tripartite motif-containing protein 27 , both of which were previously verified as negative regulators of type i ifn production. 26700765_2 taken together, these results demonstrate that en- dogenous siglec1 and trim27 are direct targets of mir-27a. 26700765_3 taken together, we conclude that mir-27a upregulates vsv-triggered type i ifn production mainly through targeting negative regulators siglec1 and trim27. 26700765_4 additionally, the cds region of both siglec1 and trim27 mrna was determined to be targeted by mir-27a 22158906_1 furthermore, overexpressing mir-1245 in mcf-7, mda-mb-231, and 293ft cells could dramatically inhibit the expression of gfp which contain brca2-3'-utr, but did not change the expression of gfp-gamma-tubulin, suggesting that mir-1245 specifically affected the brca2-3'-utr . 22158906_2 collectively, our results demonstrate that brca2 is a bona fide target of mir-1245. 22158906_3 these results suggest that the gain of mir-1245 function leads to a phenotype similar to that with the loss of brca2. 22158906_4 the results of immunoprecipitation assay showing that mir-1245 had no effect on the interaction between rad51 and brca2 further support the notion that mir-1245-induced dna damage may be through specific down-regulation of brca2. 22158906_5 these results indicate that c-myc may mediate brca2 down-regulation through up-regulation of mir-1245. 22158906_6 taken together, these results suggest that mir-1245 is required for c-myc-mediated brca2 down-regulation. 22158906_7 these data further strengthen the notion that c-myc up-regulates mir-1245 expression and down-regulates brca2 protein. 26289744_1 bmdcs were co-transfected with keap1 3'-utr reporter along with inhibitors or mimics of mir-200a, for 24 h and luciferase activity assay as then performed.results 26289744_2 indicated that mir-200a inhibitor significantly increased keap 3'-utr 1 activity and mir-200 mimic markedly reduced it , compared to the group transfected with nc. in addition, protein expression of keap1 was also up-regulated by mir-200a inhibitor and down-regulated by mir-200a mimic. 23880186_1 bioinformatics showed that lrrfip1 is a target candidate of mir-132. 23880186_2 mir-132 down-regulated luciferase activity driven by a vector containing the 3'-untranslated region of lrrfip1 in a sequence-specific manner. 26910911_1 dual-luciferase experiment confi rmed mir-27b down-regulated its target gene plk2 through the 'seed regions-'. 26910911_2 our study demonstrated that hpv16 e7 could increase dgcr8 to promote the generation of mir-27b, which accelerated cell proliferation and inhibited paclitaxel-induced cell apoptosis through down-regulating plk2. 26910911_3 mir-27b was proved to be up-regulated by hpv16 e7 through dgcr8 to promote proliferation and suppresses apoptosis by targeting plk2 in cervical cancer cells. 20170724_1 mir-22 functions as a micro-oncogene that can invert the functionality of pten. 18667440_1 in this study, we demonstrated that c-myb is an evolutionary conserved target of mir-150 in human and zebrafish using reporter assays. 18667440_2 we thus measured the c-myb mrna levels in ccrf-cem by quantitative rt-pcr in the parallel transfection experiment as in figure 3a. as illustrated in figure 3b, transfection with pre-mir-150 led to a reduction of c-myb mrna to 73% of the pre-ctrl or pre-mir-198 transfections. 18667440_3 this finding suggests that mir-150 represses c-myb gene expression at both mrna and translational levels. 18667440_4 in this study, we have demonstrated that c-myb genes of both human and zebrafishare negatively regulated by mir-150. 18667440_5 both 3'-utrs of human and zebrafishc-myb genes contained targetsites of mir-150, mutations of which sequences to mismatch to the seed region of mir-150 were able to reverse the mir-150 repression. 26891291_1 taken together, these results strongly suggested that mir-9-5p, mir-675-5p, and mir-138-5p decreased gsk3-beta, atp8a2, and eif4ebp1 by directly binding to their 3'-utr. 23951316_1 our results confirmed that vegfa is a direct target of these mirnas, as both mir-29a,c and mir-203 strongly and specifically suppressed endogenous vegfa expression in vitro. 23951316_2 figure 4 mir-203 and mir-29 directly target vegfa mrna. 26634350_2 mir-125b, mir-146a, mir-150 and mir-214 as candidate mirnas responsible for observed inhibitory effect of hsf1 on huntingtin expression. 24727952_1 hcv infection decreased mir-942 expression in hlcz01 cells and mir-942 was inversely correlated with isg12a expression in both hcv-infected cells and liver biopsies. 24727952_2 mir-942 forced expression in hlcz01 cells decreased isg12a expression and subsequently suppressed apoptosis triggered by hcv infection. 26902422_1 furthermore, restoring let-7a expression significantly decreased the levels of stat3 mrna and protein of es cells . 26080461_1 the basis for using this assay is that the hybridization between mir-3145 and the viral pb1 target that linked with 3'-utr of the firefly luciferase gene will trigger silencing of firefly luciferase activity compared to a control. in this group, the a549 cells could overexpress hsa-mir-3145 to hybridize with a viral pb1 target region presented at 3'-utr of the reporter gene. 26080461_2 interestingly, the relative luciferase activity in group 6 was significantly lower than those found in group 1 and group 4 controls , indicating that hsa-mir-3145 triggered approximately a 63% reduction of the luciferase activity by targeting the viral pb1 segment within the 3'-utr of the firefly luciferase reporter gene. 21207483_2 mutated bmi1 3'utr was resistant to mir200c targeting . 21207483_3 collectively, these data indicated that mir200c is inversely correlated with, and directly target, bmi1 expression in hnscc pathogenesis. 25015418_1 the interaction between cd133 and mir-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. 25015418_2 thus, mir-142-3p directly targets cd133 to regulate its ability to confer cancer and stem cell-like features in hcc. the bona fide interaction between cd133 and mir-142-3p was validated by luciferase reporter assays. 25015418_3 functional studies in vitro and in vivo found mir-142-3p to regulate the ability of hcc cells to confer cancer and stem cell-like properties, via the direct targeting of cd133. 21960590_1 human mir-27a* specifically bound to the 3'untranslated regions of prf1 and gzmb, down-regulating expression in both restingand activated nk cells, and it functioned as a fine-tuner for homeostasis of the net amount of the effector proteins. 21960590_3 interestingly, mir-27a* was identified as a possible suppressor of both prf1 and gzmb mrna . 21960590_4 these results suggested that human mir-27a* is a negative regulator of prf1 and gzmb expressions during activation. 21960590_5 furthermore, little differences in the decay rate of reporter mrnas containing prf1 or gzmb 3- utr were observed using an actinomycin d chasing assay, either with or without mir-27a* overexpression , indicating that mir-27a* suppresses prf1 and gzmb expression by translational inhibition. 21960590_6 taken together, these data suggest mir-27a* down-regulates both prf1 and gzmb expression by specifically targeting their 3- utr sequences. 21960590_7 taken together, these results demonstrate that mir-27a* down-regulates nk-cell cytotoxicity through targeting effector prf1 and gzmb expression. 24512851_1 binding sites were confirmed between hsa-mir-125b and sirt7/malat1.upregulation of hsa-mir-125b or downregulation of sirt7 inhibited proliferation, motility and increased apoptosis. 22581522_1 in summary, these data suggest that klf6 gene is a direct target of mir-181a and mir-181a functions as anoncomir in gastric cancer by repressing the expression of tumor suppressor klf6. 22581522_2 mir-181a is overexpressed while klf6 is downregulated in gastric cancer tissues. 22581522_3 mir-181a inhibits the expression of klf6 by targeting its 3'-utr. 22581522_4 to verify that klf6 is a functional target of mir-181a, we cloned a reporter plasmid containing the wide-type 3'-utr of klf6 at the 3-position of the firefly luciferase reporter gene. 22581522_5 to confirm that mir-181a represses klf6 expression in sgc-7901 cells, we performed western blot analysis. 22581522_6 rt-pcr analysis showed that the transfection of mir-181a mimic led to a significant decrease in klf6 mrna level. 22581522_7 taken together, these data provide evidence that mir-181a inhibits the expression of klf6 by directly targeting the 3'-utr of klf6. 20841506_1 furthermore, in pmir-bim-3'-utr mutant transfected jeko-1 cells as well as sudhl-4, no changes in reporter activity were observed . in addition, anti-搈ir-181a increased the luciferase activity in pmir-bim-3'-utr but not in pmir-bim-3'-utr mutant-搕ransfected jeko-1 cells . 20841506_2 taken collectively, these data indicate that bim is a direct target of mir-181a. 20841506_3 mir-181a directly target bim and mediates cell adhesion-induced bim down-regulation. 20841506_4 these results, for the first time, demonstrate that the level of bim and cell apoptosis is tightly controlled by the interaction with surrounding fdcs via induction of mir-181a. 19551852_1 our results show the 3'utr of efna3 is regulated by mir-210 and inhibition of mir-210 reduces efna3 protein levels as well as clonogenic cell survival of mcf-7 cells. 19437538_2 these results suggest that mir-125b functionally recognized the mre125b on the human vdr mrna. 19437538_3 these results suggest that the endogenous vdr level was repressed by mir-125b. 23227829_3 luciferase reporter assay confirmed that mir-383 negatively regulated prdx3 by interaction between mir-383 and complementary sequences in the 3' utr of prdx3. 21418558_2 hence, mir-449 directly target cell cycle regulator genes consistent with a tumour suppressor function and with the cell cycle arrest observed upon mir-449 re-introduction into cancer cell lines. 26383248_1 several studies have shown that smad7 is targeted by mir-21. 26383248_2 our study is consistent in showing that mir-21-m decreases smad7 expression and that mir-21-i increases smad7 expression. 26810470_1 the expression of pten, a functional target gene of mir-21 in bmsc, was regulated by mir-21. 26810470_3 these results indicate that pten is a potential target gene of the mir-21-mediated protective effects against h2o2 in bmsc. in conclusion, our data reveal that mir-21 protects bmsc from h2o2-induced injury and apoptosis through the akt pathway by targeting pten. 17220301_1 the microrna let-7a modulates interleukin-6-dependent stat-3 survival signaling in malignant human cholangiocytes. 18413744_1 our results show that mir-221 and mir-222 both directly targetthe 3 untranslated regions of p27 and p57 mrnas to reduce reporter gene expression, as well as diminish p27 and p57 protein levels. 18413744_2 mir-221 or mir-222 oligonucleotides significantly reduced p57 3'utr-luciferase and p27 3'utr-luciferase reporter activities by 60% and 77%, respectively . 19926638_1 subsequently, the tumor suppressor retinoblastoma was confirmed to be a direct target of mir-675 as the microrna suppressed the activity of the luciferase reportercarrying the 3'-untranslated region of rb messenger rna that contains the mir-675-binding site. 19926638_3 as the target of mir-675, the level of rb protein also appears to be negatively correlated with the levels of both h19 and mir-675 in the human colon cancer cells . 26719145_1 the 3' untranslated region in vitro reporter studies confirmed igf1 and tnc as targets of mir-489. 26719145_2 while mir-489 was of epithelial origin and present in exosomes, its targets igf1 and tnc were produced by fibroblasts. 26403328_1 importantly, brca1 is a target gene of mir-483-3p by rna-seq analyses and the downregulation of mir-483-3p may be the mechanism for liver mdb formation since the brca1 signal was markedly upregulated in ah livers. 26403328_3 the downregulation of mir-483-3p, which increases brca1 expression might provide the mechanism of brca1 expression was increased in the livers from ah and the ddc re-fed mice. 22438230_1 luciferase reporter assay showed that mir-20b target ephb4 and ephrin-b2 that have been shown to be critical for early human placental development. 26837415_1 we demonstrated that eya2 is a direct target of mir-30a by using the dual-luciferase reporter assay in a549cells and showed that eya2 protein levels are inversely correlated with mir-30a expression in a549 and beas-2b cells. 26837415_2 this result indicated that mir-30a inhibited the expression of eya2 by directly targeting its 3- utr. 26837415_3 all these data demonstrated that eya2 was a direct target of mir-30a in lung adenocarcinoma cells. 21684154_1 we performed functional assays using the 3'utr of the c-myc gene as a mir-429 targetin a luciferase reporter assay system. 21684154_2 we showed that c-myc protein expression was significantlydownregulated in extracts from mir-429-transfected sgc-7901 cells when compared with mir-429 control-transfected sgc-7901 cells . 22876037_1 methylation-mediated suppression of mir-373 required mbd2 enrichment at the promoter-associated cpg island, and mir-373 negatively regulated mbd2 expression through targeting the 3'utr. 22876037_2 mir-373 behaves as a direct transcriptional targetand negative regulator of mbd2 activity through a feedback loop of cpg island methylation. 22876037_3 taken together, these findings suggest that mbd2 3'utr carries a mir-373 regulatory site, and mir-373 can negatively regulate mbd2 through binding to the mirna locus of mbd2 3'utr. 25515522_1 foxp2 is a common target for a converging and interrelated set of msc-regulated mirnas. in support of this notion, and using targeted qpcr assays, we found that the expression levels of mir-199a-3p in clinical breast cancer specimens correlated with the expression levels of mir-let-7b, mir-34a, and mir-1915 . 25515522_2 consistent with foxp2 downregulation, these cells exhibited an increase in aldh1 positivity as determined by aldefluor assays, displaying 20-, 75-, 30-, and 30-fold increases by mir-let-7b, mir-34a, mir-762, and mir-1915, respectively . 22641068_1 c-met mrna, which encodes the receptor tyrosine kinase for hepatocyte growth factor, is a target of mir-449. 22641068_2 mir-449 binds c-met mrna to reduce its levels, promoting apoptosis and reducing proliferation of liver cells. 22641068_3 three kinds of experiments were performed to validate c-met as a target gene of mir-449 and to characterize its role in hepatocarcinogenesis: treatment of hcc and immortalized liver cell lines with hdac inhibitor tsa, simultaneous knockdown of hdac1- 3 by sirnas, and transfection of mir-449 into the cell line hle. 22641068_4 importantly, using a luciferase assay, we were able to provide evidence of direct binding of mir-449 to the 3'-utr of c-met. 23416459_1 functional analysis revealed that mir-30d overexpression suppresses cell proliferation and induces apoptosis in rcc cells, suggesting that mir-30d acts as a tumor suppressor. in searching for downstream targets of mir-30d, we found that mir-30d post-transcriptionally suppresses expression of the oncoprotein metadherin by destabilizing its mrna. 20980664_1 fig. 1. a functional runx2 dna binding site regulates expression of the mir-23a- 27a~24-2 cluster and mir-23a regulates runx2. 20980664_2 taken together, the reciprocal expression pattern between runx2 and the mir cluster and mir-23 control of runx2, validated by specific binding site mutation analysis, suggest a regulatory loop between runx2 and the mir cluster to regulate the osteoblast phenotype at multiple stages. 20980664_4 reporter assays in mc3t3-e1 cells using satb2 3'-utr-luc for each mir showed that exogenous expression of individual mirs significantly repressed the luciferase activity . 20980664_5 additionally, satb2 protein was repressed several fold by both premir-23a and -27a ; however, stability of the mrna was unaffected . 20980664_7 thus, the inhibitory effect of the mir-23a~27a~24-2 cluster on osteogenesis is contributed by the activity of all three mirs mediating translational control of satb2 mrna. 22573352_1 the transcript for tmem88 gene has a mir-708 binding site in its 3' utr and was significantly reduced in tumors high of mir-708. 22573352_2 mirna-708 acts as an oncogene contributing to tumor growth and disease progression by directly downregulating tmem88, a negative regulator of the wnt signaling pathway in lung cancer. 22573352_3 tmem88 is a potential downstream target of mir-708. 22573352_4 furthermore, the mrna level of endogenous tmem88 decreased in a dose-dependent manner in cells overexpressing mir-708 . 22573352_5 using mirna and mrna gene expression profiling and integrated bioinformatics analysis, we identified the transcript tmem88 as one of the candidate target of mir-708 . 26157346_2 to generate 3' utr mutant of cdca7 mrna containing mutations of conserved mir-4331 binding site, the site-directed mutagenesis was performed using the dna sequence of wild-type 3' utr as the template. 26157346_3 the results showed that the mir-4331 mimics decreased the cdca7-wt reporter activity and the mir-4331 mimics and inhibitors had specific binding activity . 26157346_4 to determine whether mir-4331 inhibits cdca7 expression, mir-4331 mimics or mimics control was transfected into pk-15 cells, and cdca7 expression was assessed by western blot. 26157346_5 together, our data conclusively demonstrate that cdca7 is a direct target of mir-4331 in pk-15 cells. 21236257_1 these results strongly suggest that cd40l is among the target genes of mir-146a. 21236257_2 the reporter gene assay showed that, compared with that in pgl3-cd40l-3'-utr plasmid co-transfected cells, the activity in cells co-transfected with the anti-mir-146a, and premir-146a markedly increased and decreased . 21236257_3 this finding suggests that mir-146a directly target cd40l. 21236257_4 therefore, the data suggest the essential role of cd40l in mir-146a-mediated inflammatory effects on ox-ldl-induced dcs. 21236257_5 significantly, our results highlight the role of the target gene cd40l in its responses to mir- 146a interaction, providing a novel therapeutic approach to the treatment of atherosclerosis. 23967293_1 dnajb1 was associated with seed sequence mir-199a-3p whereas both dnajb1 and hspa1a were associated with seed sequence mir-34a-5p . in particular mirna seed sequences mir-199a-3p and mir-34a-5p were associated with highest-ranking fold change genes hspa1a and dnajb1. 25175916_1 target analysis showed that a potent -beta-catenin inhibitor, icat/ctnnbip1 was a direct target of mir-424-5p. 25175916_2 further study demonstrated that mir-424-5p reversed resistance to anoikis and emt of hccs by directly targeting icat and further maintaining the e-cadherin/-beta-catanin complex on the cellular membrance. 25175916_3 these data suggested that icat was a direct target of mir-424-5p. 25142507_1 to address that mir-155 simulta-neously interacts with the target sequence localized inthe 3'-utr of tcf4 and agtr1 predicted by our previ-ous computational algorithms. it was found thatmir-155 decreased the luciferase activity of tcf4 3'-utr by 78.6% and agtr1 3'-utr by 40.6% , indicating that mir-155 exerted its direct inter-ference via both tcf4 and agtr1 mrna translation. 25142507_2 west ern blot further demo nstrated thatdecrease in mir-155 could reinforce emt process andexpression of phosphorylated erk1, rsk2 and ras bytargeting tcf4 and agtr1 simultaneously to promoteactivation of quies cent primary hsc. 26572075_1 taken together, these results suggested that the expression of bim was negatively regulated by mir-181b, which may play an essential role in the dox resistance of breast cancer cells. 24736504_1 moreover, we found that mir-338 inhibited gastric cancer cell migration, invasion, proliferation and promoted apoptosis by targeting nrp1 expression. 26283227_1 we have identified mir- 181a as a hkii-targeting mirna and h 2 o 2 increased the expression of mir- 181a in mscs. 26283227_2 this indicated that mir-181a directly targeted the 3'-utr of hkii . in summary, we demonstrate that anti-mir-181a attenuates cell death of mscs exposed to h 2 o 2 through suppression of mir-181a and subsequent down-regulation of hkii. 23190898_1 the luciferase reporter assays further demonstrated that mir-26a can repress gene expression through the binding site in the 3' untranslated region of sodd . 23190898_2 we found noticeably increased levels of sodd in cells treated with the mir-26a inhibitor at 72 hours , indicating that endogenous mir-26a has a repressive effect on sodd. 23190898_3 these results demonstrated that mir-26a can repress gene expression through the mir-26a binding site in the sodd 3' utr. 23190898_4 we have identified the antiapoptotic protein sodd as a target of mir-26a, and found that specific knockdown of sodd produces cell death in some, but not all, cell lines sensitive to mir-26a. 22841487_1 under reduced hur levels, lincrna-p21 accumulated in human cervical carcinoma hela cells, increasing its association with junb and ctnnb1 mrnas and selectively lowering their translation. 22841487_2 lincrna-p21 selectively interacts with targetctnnb1 and junb mrnas. 22841487_3 it remains to be determined whether other mrnas are translationally repressed by lincrna-p21 in this manner, as well as the fractions of junb and ctnnb1 mrna pools that associate with lincrna-p21. 22841487_4 these effects were not due to changes in ctnnb1 or junb mrna levels , nor were they due to changes in -beta-catenin or junb protein stability , suggesting that lincrna-p21 likely reduced translation of ctnnb1 and junb mrnas. 26252661_1 mir-34a reduces the expression of bcl-2 and sirt1. 26252661_2 the levels of sirt1 in the mir-34a inhibitor group were significantly elevated compared with the mir-34a mimics group , however, the sirt1 levels were not significantly different from the control group. 26252661_3 the levels of bcl-2 in the mir-34a inhibitor group were marginally elevated compared with the mir-34a mimic and the control groups, however the difference was not significant. 23467423_1 col2a1 and tpm1 were confirmed to be new, direct targets of mir-29c. 23467423_2 moreover, we identified tpm1 and col2a1 as new target genes for mir-29c. 22572890_1 correspondingly, mir-126, which has a targetregion within the 3'-utr of vcam-1 mrna, was increased 2.79-fold by the we at 100 渭g gae ml . 22572890_2 previous studies have demonstrated that mir-126 inhibited the expression of vcam-1 and therefore decreasing mir-126 in endothelial cells increases tnf-a-stimulated vcam-1 expression and enhances leukocyte adherence to endothelial cells. 22572890_3 the we treatment at 50 渭g ml 1 enhanced the expression of mir-126 up to 9.6-fold in comparison with the control cells and decreased the vcam-1 protein levels, confirming the effects of the we on the mir-126-vcam-1 interactions . 26470728_2 mir-711 targets 3'-utrs of akt mrna. 26470728_3 these data demonstrate that mir-711 targets the 3'-utr of akt mrna and inhibits expression of akt. 21809359_2 mir-494 directly interacts with the 3'utr of cdk6 and results in a decrease of cdk6 at protein level. 21809359_3 b. mir-494 directly interacts with binding site in the 3'-utr of cdk6. 26036598_1 an in vitro study using dual luciferase reporter assay demonstrated that mir-185 likely targets the 3'-utr of sstr2 mrna in the rat pituitary adenoma gh3 cell line. 26036598_2 mir-185 also downregulated or upregulated the expression of sstr2 mrna and sstr2 protein, following transfection with mir-185 mimics or inhibitors, respectively. 26036598_3 mir-185 directly targeted and degraded sstr2 mrna. 22393241_1 lass2 is a direct targetfor mir-221 and mir-222. 22393241_3 further studies revealed that longevity assurance homologue 2 was a direct target of mir-221/222 in scs because mir-221/222 bound directly to the 3'-untranslated region of lass2, thus reducing both mrna and protein levels of lass2. 22393241_4 taken together, these findings show that inhibitory action of lass2 could abrogate anti-mir-221/222-induced cell proliferation and migration suppression, suggesting that lass2 is a functional mediator for mir-221/222 in scs. 21763284_1 tumor necrosis factor alpha-induced protein 3 , a key regulator in inflammation and immunity, was found to be inversely correlated with mir-29c levels and was identified as a target of mir-29c. 21763284_2 this result indicated that tnfaip3 was a direct target of mir-29c. 21763284_3 transfection with ps-mir-29c reduced tnfaip3 protein levels compared with cells transfected with ps-control and compared with untreated cells, which was consistent with the changes in the mrna expression levels . 21763284_4 fig. 1.mir-29c expression was downregulated in hbv-related hcc and tnfaip3 is a putative target of mir-29c. 22441107_1 sqstm1 , a multiple domain protein that acts as a signaling hub, was identified as a key target for these mirnas. 26823491_3 taken together, all these results revealed that mir-199b-5p antagomir blocked the effects induced by tigecycline and demonstrated that tigecycline inhibited cell proliferation by regulating mir-199b-5p-hes1-akt pathway in glioma. 26568291_1 figure 4 mir-186 targeted skp2 to suppress its expression. 26568291_2 these results provide evidence that mir-186 can directly target the 3'-utr of skp2 mrna, resulting in suppression of its translation. 25041019_2 these observations indicate that mir-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. 19276373_2 here, we show that mir-205, down-modulated in breast tumors compared with normal breast tissue, directly targets her3 receptor, and inhibits the activation of the downstream mediator akt. the reintroduction of mir-205 in skbr3 cells inhibits their clonogenic potential and increases the responsiveness to tyrosine-kinase inhibitors gefitinib and lapatinib, abrogating the her3-mediated resistance and restoring a potent proapoptotic activity. 10716699_1 the nespas transcript therefore either may be less stable or only weakly expressed but, even so, still able to regulate the silencing of the sense nesp transcript from the paternal allele.northern 10716699_4 the detection of both nesp and nespas transcripts from opposite parental alleles in heart supports a proposal that antisense controls expression of the sense transcript from the paternal allele. 15601474_1 these data suggest that nef/u3 mirnas produced in hiv-1-infected cells may suppress both nef function and hiv-1 virulence through the rnai pathway.nef-derived 15601474_2 mirnas are produced in hiv-1 persistently infected cells and nef short hairpin rna that corresponded to a predicted nef mirna can block hiv-1 nef expression in vitro and the suppression by shrna/mir-n367 would be related with low viremia in an ltnp . 22537941_1 overexpression of mir-29a/b/c also promoted apoptosis by decreasing the level of the antiapoptotic protein mcl1. 26648141_1 the results of the luciferase assay showed that the relative luciferase activities in the let-7a-overexpressing pca cells transfected with wild type 3'-utr of igf1r were substantially lower than those cells transfected with mutant 3'utr of igf1r , suggesting that igf1r was an effective target of let-7a with the "seed sequence" in the 3'utr acting as the binding site of the mirna. 26648141_2 luciferase assay showed that only the luciferase activity in lncap cells transfected with let-7a mimics and wild-type 3'utr of igf1r were significantly decreased. 23991130_3 downregulated or upregulated ing4 expression could partially rescue the effects of mir-650 inhibitor or mimics in docetaxel-resistant or parental lad cells. 23991130_4 furthermore, we found that ing4 was upregulated in docetaxel-responding lad tissues, and its expression was inversely correlated with mir-650. 23991130_5 thus, mir-650 is a novel prognostic marker in lad and its expression is a potential indicator of chemosensitivity to docetaxel-based chemotherapy regimen. 26562529_1 these data demonstrated that the mir-543 targeted the sirt1 via binding with the sirt1 3'-utr. 26562529_2 showed that the mrna level and the protein level of the sirt1 was significantly down-regulated or up-regulated by the mir-543 overexpression or inhibition in the hepg2 cells, respectively . 19276261_1 to evaluate the role of microrna-21, cell proliferation and invasion were analyzed with anti-microrna-21-transfected cells. in addition, the regulation of pdcd4 by microrna-21 was elucidated to identify the mechanisms of this regulation. 19276261_5 all seven esophageal squamous cell carcinoma cell lines also overexpressed microrna-21, and anti-microrna-21-transfected cells showed significant reduction in cellular proliferation and invasion. 19276261_6 the pdcd4 protein levels in esophageal squamous cell carcinoma cells have an inverse correlation with microrna-21 expression. 19276261_7 anti-microrna-21-transfected cells increased pdcd4 protein expression without changing the pdcd4 mrna level and increased a luciferase-reporter activity containing the pdcd4-3' untranslated region construct. 19276261_8 conclusions: microrna-21 targets pdcd4 at the posttranscriptional level and regulates cell proliferation and invasion in esophageal squamous cell carcinoma. 14622403_1 some of the positive gene signals correspond to known hfq targets such as ompa or known small rna targets such as nlpd . 12242501_1 suppression by snr10 efficiently rescues the slow-growth and temperature-sensitive phenotypes of the rrp5 mutant strain and is specific for this small nucleolar rna. 12242501_2 so the snr10 suppresses th rrp5. 23079745_1 our findings suggest the oncogenic potential of sirt7 in hepatocarcinogenesis. a regulatory loop is proposed whereby sirt7 inhibits transcriptional activation of p21 by way of repression of mir-125a-5p and mir-125b. 23079745_3 overall, these results demonstrated that both mir-125a-5p and mir-125b are direct suppressors of endogenous sirt7 and may function as tumor suppressors in hcc tumorigenesis. 22963823_1 to search for a possible involvement of mir-467b in the regulation of lpl, we scanned the 3'utr sequence of the mouse lpl transcripts using two databases: microcosm targets , and rnahybrid . 22963823_2 we found that mir-467b is predicted to bind to mouse lpl 3'utr based on the two databases . 22963823_3 based on analyses of prediction algorithms, we performed luciferase reporter assays to determine if mir-467b speci铿乧ally targets lpl post-transcriptionally by binding to its 3'utr. 22963823_4 the 3'utr of the lpl gene containing mir-467b recognition sites was cloned from raw 264.7 cells by rt-pcr and inserted downstream to a luciferase reporter.taken 22963823_5 together, these 铿乶dings demonstrate that mir-467b directly targets the lpl gene.we 22963823_6 also examined the effect of mir-467b on endogenous lpl expression in raw 264.7 cells. 22963823_9 data demonstrate that mir-467b regulates the expression of lpl by targeting the lpl 3'utr to facilitate mrna degradation or translational repression in macrophages. 19738052_3 two snps, rs1970801 and rs11097457, scoring in the top 100 from the cgems study, were in strong linkage disequilibrium with rs1434536, an snp that resides within a mir-125b target site in the 3' untranslated region of the bone morphogenic receptor type 1b gene encoding a transmembrane serine/threonine kinase. 19738052_6 furthermore, luciferase reporter assays and overexpression of mir-125b-mimics combined with quantitative reverse transcription-pcr showed that bmpr1b transcript is a direct target of mir-125b and that mir-125b differentially regulates the c and t alleles of rs1434536. 19738052_7 these results suggest that allele-specific regulation of bmpr1b by mir-125b explains the observed disease risk. 26908827_1 irak1 and traf6 are the 2 important molecular targets of mir-146a, based on the targetscan prediction for mirna targets . 26908827_3 we also observed a reduction of irak1 and traf6 protein levels under heterologous lps tolerance conditions compared with nontolerized control cells , suggesting that the mir-146a-induced reduction of these adaptor molecules might contribute to lps-induced heterologous tolerance to other tlr ligands. 26908827_4 as mir-146a inhibits the translation of irak1 and traf6, we evaluated the protein levels of these molecules in thp-1 macrophages. 26396669_1 mir-29c targets cdk6 and regulates its expression in mir-29c targets cdk6 and regulates its expression in t24 cells. 22418008_1 the expression of the prosurvival bcl-2 family member mcl-1 was downregulated in both mir-125a-overexpressing iec-6 cells and in jejunum of resected rats, confirming mcl-1 as a previously undiscovered target of mir-125a. 22418008_2 these findings confirm that mcl1 is a target of mir-125a and may mediate the proapoptotic effects of mir-125a in iec-6 cells. 22418008_3 mir-125a suppresses the prosurvival protein mcl1 in enterocytes. 22418008_4 our results suggest that one role of mir-125a in intestinal adaptation is to activate the apoptotic pathway, in part by suppressing expression of the antiapoptotic mcl1. 20372864_1 inhibition of c-flip expression by mir-512-3p contributes to taxol-induced apoptosis in hepatocellular carcinoma cells. 17297439_1 we demonstrate that mir-34a directly target the messenger ribonucleic acid encoding e2f3 and significantly reduces the levels of e2f3 protein, a potent transcriptional inducer of cell-cycle progression. 17297439_2 overexpression of mir-34a reduced the luciferase activity from the reporter construct containing the e2f3 site and the positive control , whereas no effect was observed with a construct containing a mutated e2f3 seed site . 17297439_3 western blot analysis of sk-n-as cells transfected with mir-34a showed a significant reduction in e2f3 protein in cells overexpressing mir-34a, confirming that mir-34a target e2f3 mrna . 21271679_1 luciferase and mutation assays validated that txnip and rabep1 were the direct targetgenes of mir-373. 21271679_3 these observations suggested that the expression of txnip and rabep1 was directly regulated by mir-373 through their 3'-utr regions, implicating txnip and rabep1 as the direct targetgenes of mir-373. 21225631_1 therefore, mir-9 might repress cdx2 expression via the binding site in the 3'-utr, resulting in the promotion of cell proliferation in gcs. on the other hand, the reporter vector lacking the mir-9 recognition site fully rescued the mir-9 repression of luciferase activity , indicating that only mir-9 directly and specifically interacts with the targetsite in the cdx2 3'-utr. 21225631_2 figure 1. interaction of mir-9 with its binding site in the cdx2 3'-utr. 21225631_3 overall, mir-9 was likely to have an effect on cdx2 expression in gc cell lines. 21225631_4 overall, these results demonstrated that mir-9 did not considerably affect mrna stability, but rather inhibited cdx2 expression by blocking protein translation. 22606351_1 this study has demonstrated that in the absence of p53 and p16, the induction of senescence by dox was associated with upregulation of mir-375 and autophagy initiation. 22606351_2 the anti-proliferative function of mir-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and sp1 genes. 22158047_1 our results demonstrate that pkcepsilon is directly regulated by mir-107 and moreover, suggest that mir-107 may be a potential anti-cancer therapeutic for hnscc. 22158047_2 these results provide evidence to demonstrate an inverse association between mir-107 and pkcepsilon in hnscc. 22158047_4 our work confirmed that mir-107 regulates pkcepsilon through direct binding in the 3'-utr of the pkcepsilon mrna and moreover, optimal suppression of pkcepsilon requires occupation of all three mir-107 sites. 22158047_6 taken together, these results indicate that down-regulation of pkcepsilon by mir-107 is an effective approach to suppress the tumorigenicity of hnscc in vitro and in vivo. 26273428_1 further bioinformatic analysis, coupled with in vitro luciferase assays, determined that mir-451a and mir-21-5p can target the oxytocin receptor gene. 26273428_3 we note that mir-451a induced a stronger downregulation of the oxtr 3'-utr activity in the luciferase assays, while only mir-21-5p was correlated with oxtr expression in the human brain. 21324897_1 we presumed that mir-3960 promoted osteoblast differentiation by binding with the cds of hoxa2. 21324897_2 thus, these results demonstrated that mir-3960 directly targeted hoxa2 by specifically binding with the target cds of hoxa2. 21324897_3 these results revealed that mir-3960 post-transcriptionally repressed hoxa2 protein expression by inhibiting mrna translation and not by mrna degradation. 26801758_2 epcs transfected with mir-483-3p agomir exhibited significantly decreased srf protein level while epcs tranfected with mir-483-3p antagomir exhibited increased srf protein level . 23522925_1 these data indicated that mir-203 had a potential to regulate immune response in macrophages through a mechanism in part by post-transcriptionally down-regulating myd88 expression. 23522925_3 collectively, the results reported in this study suggest that myd88 is a novel target of mir-203. 23522925_4 we reasoned that: mir-203 target the 3'utr of myd88 mrna via binding its 2- 8 seed sequence, by which it may not efficiently inhibit thr transcription, as compared with sirna. 22998082_1 experi ments with the mir-34a antagomir revealed that targeting mir-34a led to an inhibition of activated caspase-3 protein expression, which may contribute to increased neuronal survival and reduced neuronal death or apoptosis. 26166175_1 the data from the luciferase report plasmid analysis showed that overexpression of mir-146a attenuated tslp mrna 3'-utr activity. 26166175_3 on the contrary, knock-down of mir-146a induced increase of activity of tslp mrna 3'-utr, as well as enhanced mir-146a expression of mrna and protein . 26708293_1 notably, we identified phosphatase and tensin homolog as a direct downstream target and functional mediator of mir-519a in hcc cells. 26708293_2 finally, we identified pten and pi3k/akt pathway as direct targets of mir-519a. 26708293_3 collectively, these results strongly suggest that pten is a downstream target of mir-519a in hcc. 26708293_4 moreover, we identified pten as a novel direct target of mir-519a. 20937378_1 following the expression study above, and the identification of sox9 as a potential target of mir-124 in the adult mouse svz, embryonic spinal cord tissue was examined, by in situ hybridization, for both mir-124 and sox9 . 21291913_1 up-regulation of mir-101 expression may play a role in repressing productive hsv-1 replication by targeting atp5b. 21291913_2 these results suggested that mir-101 could directly bind to the 3' utr of atp5b mrna and specifically suppress targetgene expression. 21291913_3 this indicated that mir-101 negatively regulates atp5b expression at a post-transcriptional level, which is consistent with the results of the egfp reporter assay. 26856603_1 additionally, the rs11014002 snp promotes the biogenesis of mature mir- 603. 26856603_2 mir- 603 downregulates lrpap1 mrna and protein levels through directly binding the 3- untranslated region of lrpap1. 26856603_3 collectively, these results suggested that mir-603 can downregulate the lrpap1 mrna and protein levels by directly binding to its 3'-utr. 26856603_4 moreover, we demonstrated that mir-603 directly targets lrpap1 and upregulates lrp1 protein levels. 25211095_1 lt--beta appeared in all 3 databases as one of the best targets for the mir-155-3p. 25211095_2 direct regulation of lt--beta by mir-155-3p through complementarity to 3'-utr of lt--beta. 25211095_3 therefore, luciferase reporter assay was performed to validate if lt--beta is a direct target of mir-155-3p. 22718995_1 these results indicate that mir-204 likely directly targets the 3- utr of hmga2 mrna, representing an alternative pathway that could regulate malignant transformation and progression in mpnsts. 22916024_1 thus, consistent with the observed function of nrarp during early thymocyte development , these results demonstrate that nrarp mrna is likely a functional target of mir-181a in early thymocyte development. 22916024_2 together, our data show that the predicted mir-181a binding sites in the nrarp 3'-utr are targeted by endogenous mir-181a during early t cell development. 26513016_1 overexpression of mir7 mimic reduced raf-1 3'-utr luciferase activity in 231/lap clones .7g. in addition, our data reveled that the ago2 binding activity on raf-1 3'-utr was also reduced by mir-7 inhibitor in rna-ip analysis .7h. these results indicate that lapatinib treatment induced il-6 production through de-repression of raf-1 via downregulating mir-7. 26884832_1 transfection of mir-30a-5p mimic led to a markedly reduced aeg-1 protein level and further dual luciferase reporter assay confirmed that aeg-1 was one of the target genes of mir-30a-5p in hcc cells. 26884832_2 aeg-1 as a direct target gene for mir-30a-5p in hcc hepg2 cells. 26748705_1 mir-122 binds to three sites on the sirt6 3 ' utr and reduces its levels. 26748705_2 mir-122 binds to sirt6 3 ' utr and represses its levels, whereas sirt6 downregulates mir-122 by deacetylating h3k56 on its promoter region. 26748705_3 these findings suggest that mir-122 regulates sirt6 expression. 26748705_4 altogether, these findings demonstrate that sirt6 is a target for mir-122 regulation. 25210796_1 these data suggest that dnmt3a is a direct target of mir-101 in lung cancer cells. in this report, we identified dnmt3a as a bona fide target of mir-101 in lung cancer. 25210796_2 these investigations revealed that mir-101 levels were negatively correlated with dnmt3a expression, suggesting that dnmt3a and mir-101 have functional and regulatory interactions in lung tumorigenesis. 26876200_1 mir-223 downregulated the local expression of epidermal growth factor , leading to decreased activation of egf receptor on target cells and, eventually, dampening a positive egf-揈gfr autocrine/paracrine stimulation loop induced by the post-surgical wound-healing response. 26876200_2 overall, we demonstrated that egf is a bona fide mir-223 target and its reduced expression and secretion in mir-223 overexpressing cells is able to reduce egfr signaling pathway activation. 26876200_3 accordingly, our in vitro and in vivo analyses support that, in the context of wound-induced bc growth, expression of mir-223 has the potential to suppress tumor growth, at least in part through the downmodulation of egf expression and the inhibition of egf/ egfr autocrine/paracrine stimulatory loop, initiated by the wound-healing response. 26163264_1 accordingly, we propose that pik3cg is a direct and functional downstream target of mir- 502 in hcc cells 26299668_1 expression of gr alpha is downregulated by mir- 30a interference, however, the 3'-utr and cds of gr alpha are indirect mir- 30a targets. 26299668_2 however, co-transfection of murine cells with 50 nm mir-30a mimics revealed no change in luciferase activity of the vectors, therefore, demonstrating that mir-30a binds to either the 3'-utr or cds of gr alpha . 26299668_3 the data also indicated that mir-30a negatively regulated gr alpha in normal and injured podocytes induced by puromycin aminonucleoside . 23801152_2 this study demonstrated for the first time that the downregulation of arhi in breast cancer cells could be regulated by mir-221. 19540598_2 here we provide evidence in human neural cells of an aluminum-sulfate- and reactive oxygen species -mediated up-regulation of an nf-kappab-sensitive mirna-146a that down-regulates the expression of complement factor h , an important repressor of inflammation. 19540598_5 an nf-kappab-containing mirna-146a-promoter-luciferase reporter construct transfected into hn cells showed significant up-regulation of mirna-146a after aluminum-sulfate treatment that corresponded to decreased cfh gene expression. 19540598_6 these data suggest that as in ad brain, nf-kappab-sensitive, mirna-146a-mediated, modulation of cfh gene expression may contribute to inflammatory responses in aluminum-stressed hn cells, and underscores the potential of nanomolar aluminum to drive genotoxic mechanisms characteristic of neurodegenerative disease processes. 24402230_1 qpcr and western blot assays we showed that overexpression of mir-195-5p reduced ccne1 mrna and protein levels, respectively. 26367177_1 furthermore, the dual-luciferase reporter assay confirmed that mir-98 decreased the luciferase activity by targeting the 3- untranslated region of caspase-3. 26367177_2 in conclusion, renal iri induces up-regulation of mir-98 dependent on hif-1alpha, which protects endothelial cells against apoptosis by targeting caspase-3. 26367177_3 moreover, mir-98 targeted at the cuaccuca sequence in the 3'-utr of caspase-3 mrna directly to reduce caspase-3 protein production. 22025269_2 smmc-7721 cells have very low expression level of mir-150, but high levels of the mir-150 target gene c-myb . 22025269_3 figure 6. c-myb 3'utr is a target of mir-150. 22025269_4 these results suggested that 3'utr of human c-myb gene contains target sites specific for mir-150. 22025269_5 western blot analysis was performed to determine the effect of overexpression of mir-150 on c-myb protein expression. 22025269_6 the results demonstrated that overexpression of mir-150 in cd133+ cells significantly decreased c-myb protein expression, while the mir-control or blank control had no effect on expression of c-myb protein . 22025269_7 rt-pcr analysis demonstrated that mir-150 has little if any effect on c-myb mrna levels . 22391672_1 in addition to mir-199*, let-7b was identified, which directly targets the ns5b coding region and 5 gutr sequences of the hcv genome, resulting in a decrease in hcv replicon replication, downregulation of hcv accumulation, and reduction of hcv infectivity. 19520829_1 both mir-222 and -339 are down-regulated in dicer-disrupted cells and directly interacted with the 3' untranslated region of icam-1 mrna. 19520829_2 these data suggest that mir-222 and -339 down-regulate icam-1 expression at posttranscriptional levels by binding to the icam-1 3'-utr. 21857668_1 only mir-279 repressed expression of a reporter gene fused to the stat 3'-utr . 21857668_2 overexpression of mir-279 did not repress expression of a mutant stat 3'-utr reporter gene lacking the mir-279 seed-binding site . 21857668_3 furthermore, knock-down of endogenous mir-279 using a 2- -o-methyl mir-279 antagomir increased stat 3'-utr reporter activity in s2 cells, whereas control antagomirs did not . 21857668_4 thus, mir-279 directly targeted stat via its 3'-utr. 21857668_5 although the upd 3'-utr contained one putative mir-279 site, the upd 3'-utr reporter did not respond to mir-279overexpression . 21857668_6 thus, mir-279 targets the jak/stat signaling pathway by repressing stat. 21857668_7 taken together, these results demonstrated that mir-279 repressed stat protein expression and activity in vivo. 21857668_8 taken together, these results indicate that stat is a functional target of mir-279 in vivo. 23748970_1 flow-dependent expression of mir-21 governs valvulogenesis by regulating the expression of the same targets as mouse/human mir-21 and induces cell proliferation in the valve-forming endocardium at constrictions in the heart tube where shear stress is highest. 23748970_3 mir-21 is highly expressed in malignant tissues and has several target genes, including pdcd4, pten and spry2. 26259653_1 identification of ror2 as a target gene of mir-124. 26259653_2 according to bioinformatic analysis, ror2 is a putative target gene of mir-124. 26259653_3 mir-124 can bind directly to their seed sequences in the ror2 3'-utr. 26259653_4 when compared with that in the control group , indicating that ror2 is a direct target gene of mir-124. 26259653_5 ror2 is significantly upregulated in os cell lines and is negatively regulated by mir-124. 18758960_2 on the other hand, down-regulation of let-7a by the anti-let-7a inhibitor increased the doxorubicin-induced apoptosis in a431 parent cells, a10a cells and hepg2 cells while the increase was suppressed by caspase-3 inhibitor. 18758960_4 therefore, let-7a by targeting caspase-3 may play a functional role in modulating drug-induced cell death in human cancer cells. 22876288_1 mir-7 decreases fak expression by directly targeting its 3'-utr. 22876288_3 these results indicate that mir-7 expression is inversely correlated with fak expression and activation in breast cancer cell lines and that mir-7 directly regulates fak expression. 22876288_4 transwell assays indicated that restoration of fak expression significantly abrogated mir-7 reduced cell migration and invasiveness , indicative that fak is both a direct and functional target for mir-7. 22336716_1 results indicated that in cells co-overexpressing tmem59 and mir-351 the expression of tmem59 mrna is reduced by half compared with cells overexpressing tmem59 alone , and the change on protein levels was also detected . 21622730_3 sirt1 expression is repressed by mir-34a binding to its 3'-utr seed sequence, establishing sirt1 as a direct target of mir-34a . 21622730_4 we observed a marked decrease in sirt1 levels in mir-34a nanovector-treated xenografts as compared with vehicle control , indicating a tangible pharmacodynamic readout of mirna delivery. 21622730_5 furthermore, multiple lines of evidence point to the role of mir-34a repression in the expansion of tumor-initiating cells and that restitution of mir-34a expression depletes this subpopulation in cancers . in turn, mature mir-143 and mir-145 repress kras2 and rreb1, respectively, effectively completing the loop. 21622730_6 therefore, restitution of mir-143/145 expression in miapaca-2 xenografts should attenuate expression of both kras2 and rreb1. 21622730_8 in addition, resultant downregulation of rreb1 protein expression could be observed through immunohistochemical staining of tumor sections from both mir-143/145 nanovector-treated and vehicle control xenografts . 21622730_9 this serves as important in vivo confirmation of the aforementioned feed-forward pathway and indicates that treatment with the systemic mir-143/145 nanovector results in restitution of mature mir-143 and mir-145, with downregulation of kras2/rreb1 targets accompanying the observed tumor growth inhibition. 26140661_2 cox-2 mrna was more stable in dhuvec and this was associated with mir-16 downregulation and c-myc induction . 26140661_3 recently, microrna-16 has been identified to regulate cox-2 expression through targeting the 3'utr that leads to a concurrent reduction of cox-2 mrna and protein levels, and pge 2 biosynthesis in il-1飦 -stimulated cells. 26722415_1 to test that stc2 may be a direct target of mir-485-5p, the reporter plasmid harboring the wild-type or mutant 3'-utr region of stc2 was constructed. 26722415_2 overexpression of mir-485-5p mimics led to a reduction of luciferase activity when the reporter construct contained the stc2 3'-utr. 26722415_3 our results showed that stc2 protein levels were substantially down-regulated by mir-485-5p .6b. in contrast, inhibition of mir-485-5p led to an increased protein level of stc2 in hcc cells .6d. 25416447_1 in view of these findings, we propose that foxo1 is a direct target of mir-135b. 25416447_2 foxo1 down-regulated in os tissues is a direct target of mir-135b, to determine whether tumor promotive role of mir-135b is mediated by foxo1, we firstly investigated the role of foxo1 in os. 19265686_1 mmp16 is one of directly downstream functional target of mir-146b. 19265686_3 these data show that mmp16 is one of the functional downstream target of mir-146b for inhibiting glioma cell migration and invasion. 19265686_4 we therefore measured the mrna and protein expression levels of mmp16 in response to the changes in the mir-146b expression level in u373 cells by pre-146b or lna-anti-146b transfection. 20581857_2 furthermore, the expression of pdcd4 decreased in pc3 cells when mir-21 was ectopically expressed. 20581857_3 on the other hand, silencing of mir-21 increased pdcd4 expression in pc3r cells . 20581857_5 these findings suggest that pdcd4 is indeed a functional targetfor mir-21-induced chemoresistance to docetaxel in pc3 cells. 26801823_1 to verify whether mir-200a or mir-141 may regulate the expression of hlxb9, the dual-luciferase assay was employed. 26801823_2 these results illustrated mir-200a and mir-141 could inhibit the expression of hlxb9 by binding to its mrna 3'utr. 26399456_1 in addition, we experimentally demonstrated that pak4 was the direct target of mir-199a/b-3p, hypo-expression of pak4 suppressed proliferation, migration and invasion of mda-mb-231 cells, and overexpression of pak4 significantly rescued the inhibitory effect of mir-199a/b-3p on mda-mb-231 cell growth, migration, and invasion. 26399456_2 these findings indicated a direct interaction between mir-199a/b-3p and pak4 mrna in mda-mb-231 cells. 25701323_1 ectopic mir-23a significantly suppressed the apaf1 gene expression in pancreatic cancer cells. 23338485_1 these results strongly suggest that mir-301a negatively regulates runx3 expression post-transcriptionally. our study demonstrated that mir-301a potentially functions as an oncogene; based on our experimental evidence, we also demonstrated that mir-301a-induced proliferation and invasion depends on the expression of runx3 in the manner of directly posttranscriptional downregulation in gastric cancer. 23338485_2 therefore, we consider that runx3 should be at least one of targetgenes of mir-301a. 23338485_3 thus, the identification of the role of mir-301a as an oncogene through targeting runx3 in gastric cancer helps us to further elucidate the potential molecular mechanisms of gastric cancer development, and could potentially have diagnostic as well as therapeutic value in the future. 26316081_1 mir-497 plays an important role in inhibiting the proliferation of nsclc by targeting yap1. 26316081_2 these results confirmed that yap1 was a direct target gene of mir-497. 26316081_3 taken together, these data suggest that mir-497 suppresses yap1 expression by directly targeting the 3'-utr of the yap1 gene. 26316081_4 these data suggested that mir-497 suppresses downstream gene expression and inhibits cell proliferation by targeting yap1. 21878506_1 fig. 1.mir-216b is downregulated and is inversely correlated with the levels of kras in npc tissues and cell lines. 21878506_2 moreover, a mir-216b-binding site was found in the 3'-utr of kras mrna. 21878506_3 there was perfect base pairing between the seed sequence of mature mir-216b and the 3'-utr of kras mrna and these seed sequences were conserved across species . 21878506_4 these data suggest that mir-216b could act as a tumor suppressor by targeting kras in npc. to directly assess the effect of mir-216b on kras expression, we transfected mir-216b into 5-8f or hone1 cells and found that overexpression of mir-216b reduced kras protein levels . 21878506_5 furthermore, anti-mir-216b transfection increased kras protein levels in cne2 and np69 cells . 21878506_7 these western blotting results demonstrated that mir-216b is negative regulator of akt and erk pathways. 21878506_8 these observations suggest that mir-216b inhibits the akt and erk pathways by targeting kras. in addition, we confirmed that changes in mir-216b expression altered kras protein expression levels in lysates from mouse tumors . 26531722_1 the findings suggest that mir-125a-5p/mir-125b suppress the expression of tsta3, which controls cell proliferation and invasion by regulating cxcr4 expression. 26531722_2 the results showed that mir-125a-5p or mir-125b directly regulates tsta3. 26531722_3 the luciferase reporter gene assay confirmed that the tsta3 mrna 3- utr region contains a binding site for mir-125a/mir-125b. 20576608_1 we determined that ets1 is a targetgene of mir-208 by using a sensor luciferase reporter assay. 20576608_2 as judged by using a qrt-pcr, the levels of ets1 mrna in the cells transfected with mir-208 remained unchanged compared with bmp-2-stimulated cells . 20576608_3 thus, the increase in ets1 expression may be due to the drop in the levels of mir-208 after the bmp-2 treatment . 20576608_4 these findings suggest that mir-208 regulates the expression of ets1 at a translational level. 19697704_1 moreover, we found that induction of mir-34a led to neuronal apoptosis by targeting bcl-2. 25249556_1 ptenp1 and pten are direct targets of microrna mir-21 and their expression is suppressed by mir-21 in ccrcc cell lines. 25249556_2 taken together, these results demonstrated that both pten and ptenp1 are directly regulated by mir-21, and their expression is inversely correlated with mir-21 expression. 25249556_3 both 3'-utr of pten and ptenp1 sequences contain mir-21 binding sites. 26633009_1 peroxiredoxins are regulated by both mir-153-3p and mir-205-5p. 26633009_2 we verified the mir-153-3p- and mir-205-5p-mediated increase in prdx2 by western blot analysis . the regulation of prdxs by mir-153-3p and mir-205-5p suggest that mir-153-3p and mir-205-5p may affect cellular ros levels. 22079638_1 fig. 3.mir-34a target epha5 and regulates cell migration and condensation during chondrogenic differentiation of limb mesenchymal cells. 22079638_3 4.dedifferentiation of human articular chondrocyte by il-1-beta is possibly through mir-34-modulated epha5 level. in this study, epha5, a target of mir-34a, involves in the migration of chondroprogenitors. in sum, our data suggest that mir-34a is a negative modulator of chondrogenesis, particularly in migration of chondroblasts, by down-modulation of epha5 during chondrogenesis of chick limb mesenchymal cells. 12215442_1 bc1 and nf-l mrna bind to a similar site in the c-terminal domain of p190rhogef, and their bindings to p190rhogef are readily cross-competed. 20974966_3 therefore we investigated whether xfurry controls the expression of mir-15 and whether mir-15 functions via the rits complex. 26783084_1 we then used a relative luciferase reporter assay with the dennd2d 3- -untranslated region to demonstrate that mir-522 dramatically inhibited the luciferase activity of the wild-type 3'-utr but not that of the mutant 3- utr of dennd2d. 26783084_2 we examined the dennd2d expression level in tumor tissues and their matched normal tissues and found that dennd2d was downregulated at the mrna level, whereas mir-522 was upregulated in tumor tissues. 26783084_3 the mrna level of dennd2d measured by qrt-pcr did not significantly change, indicating that mir-522 participates in the post-transcriptional regulation of dennd2d. 20100477_1 a luciferase reporter gene experiment suggests that the 3' untranslated region of cox-2 carries a binding site for mir-26b. 20100477_2 the results suggested that mir-26b could specifically bindto the 3'-utr of cox-2 mrna and repress cox-2 expression. 20100477_3 the results support the hypothesis that cox-2 mrna is a direct targetfor mir-26b. 26391641_1 furthermore, nova1 was confirmed as a target of mir-339. 26391641_2 besides, we found that nova1 was a direct target of mir-339. 26391641_4 bioinformatic prediction and experimental analyses demonstrated that nova1 was a direct and functional target of mir-339. 25226615_1 by searching pictar, tarscan and mirbase database, we found that 3'-utr of human scgn contains putative regions that match to the seed sequence of several mirnas, including mir-494, which suggests a possible modulation of scgn by mir-494. 25226615_4 scgn expression significantly increased in h69 cells transfected with mir-494 inhibitors . 25226615_5 these findings suggest that mir-494 can directly target the 3'-utr of scgn. 12084570_1 in vitro analysis of the human par-1 promoter function revealed a positive regulatory element between -4.2 and -3.2 kb of the transcription start site. 12084570_2 further examination of this putative regulatory sequence identified a novel noncoding rna gene at -3.4 kb. the ncr-upar upregulated par-1-core promoter-driven luciferase activity and mrna expression in vitro in a pol ii-dependent manner. 26054020_1 mir-199a-5p significantly reduced the luciferase activity of the plasmid with wt hk2 3'-utr, whereas the activity of the mt plasmid remained unchanged, indicating that hk2 is a direct target for mir-199a-5p . 22320217_1 bioinformatics analysis indicated that hmbox1 was one of the potential target genes of mir-30c-1*. 22320217_2 to confirm that mir-30c-1* was able to directly bind to the 3- utr of hmbox1 and inhibit hmbox1 expression, a recombinant firefly luciferase reporter vector with a fragment of the 3- utr of hmbox1 mrna containing the putative mir-30c-1* binding sequence was cloned and co-transfected into 293t cells with either control mirna mimics, mir-30c-1* mimics or unrelated mirna mimics , respectively. 22320217_4 to demonstrate further that the downregulation of hmbox1 by mir-30c-1* was mediated through the predicted binding site, two kinds of double substitution mutations in the 3- utr of hmbox1 that disrupted the complementation with the 5- -seed-matched sites or 3- supplementary pairing sites of mir-30c-1* were generated, and it was found that both mutations abolished the repression effect mediated by mir-30c-1* on hmbox1 . 22320217_5 furthermore, to confirm that exogenous mir-30c-1* could decrease the protein level of hmbox1 in nkl cells, we transfected mir-30c-1* mimics into nkl cells and detected the protein expression level of hmbox1 . 22320217_6 the results implied that hmbox1 protein expression was inhibited by mir-30c-1* mimics. 22745684_1 when pbmcs were pre-transfected with anti-mir-34c and then exposed to lysate, expression levels of ikk纬 mrna, a putative target of mir-34c, increased, while protein levels of ikk纬 in cultures transfected with a pre-mir-34c were abrogated. 22745684_2 we also demonstrate that one of the functional targets for mir-34c could be ikk纬 an essential signaling intermediate of the nfkb inflammatory pathway. 22745684_3 these findings support the notion that ikkgamma may be a direct target of hsa-mir-34c. 23292313_1 collectively, these results suggest that mir- 21 binds to the smad7 3'-utr and downregulates smad7 abundance to derepress tgf--beta and nf-κb signalling pathways, which are enhanced in renal fibrosis and in- flammation during dn. 26033364_1 mir-101 targets the 3- utr of the abca1 mrna. 26033364_2 mir-101 directly targets site 2 on the abca1 mrna. 24676100_1 mir-224 interaction with the tcf21 transcript contributes to allelic imbalance of this gene. 23068095_1 to determine whether -beta-catenin is a direct target of mir-214, a human b-catenin 3'-utr fragment containing wild-type or mutant mir-214 binding sequence was cloned downstream of the reporter gene . 23068095_5 furthermore, we examined the changes of -beta-catenin expression in hcc hepg2 and huh-7 cells after mir-214 overexpression. 23068095_6 the results showed that overexpression of mir-214 signi铿乧antly decreased the levels of -beta-catenin protein, whereas its mrna level was constant . 23068095_7 taken together, these results strongly suggested that -beta-catenin is a direct target of mir-214 in hcc cells. 26717894_1 we further identified tgf- -beta 1 as a direct target of mir-663, and found that the expression of tgf- -beta 1 was negatively mediated by mir-663 at the post-transcriptional level in glioblastoma cells. 26717894_2 these data indicate that mir-663 directly binds to the 3'-utr of tgf- -beta 1 mrna. 26717894_3 next, we found that tgf- -beta 1 is a direct target gene of mir-663, and mir-663 negatively regulates the protein expression of tgf- -beta 1 in the glioblastoma a172 and u87 cells. 26171041_1 validation of apaf-1 as a direct target of mir-23a. 26171041_2 western blotting and rt-qpcr results indicated that mir-23a significantly decreased apaf-1 expression at the mrna and protein levels in hep2 cells . 26171041_4 these results suggest that mir-23a negatively regulates apaf-1 expression, by binding the 3'-utr nucleotides of this gene in laryngeal cancer tissues. 21737690_1 both cugbp1 and mir-222 were found to bindthe cdk4 mrna coding region and 3'-untranslated region and repressed cdk4 translation synergistically. 21737690_2 these results strongly suggest that mir-222 interacts with the cdk4 mrna and forms the complex. 21737690_3 mir-222 overexpression decreased the levels of cdk4-cr luciferase reporter activity , but it did not inhibit the activity of cdk4-3'-utr reporter activity , indicating that increasing the levels of mir-222 represses cdk4 mrna translation through interaction with the cdk4 cr rather than with its 3'-utr. 21737690_4 these results indicate that mir-222 interacts with cdk4 mrna via the specific binding site at 266- 286, thus repressing cdk4 translation. 21737690_5 together, these results support the notion that mir-222 and cugbp1 repress cdk4 mrna translation at least partially by recruiting the cdk4 transcripts to pbs following polyamine depletion. 17274687_1 therefore, considering the high sequence homology between 21a transcript and three cenp-f hnrna intronic portions, we suggest a mechanism of antisense inhibition of cenp-f mrna maturation by the 21a transcript. 17274687_2 altogether these results demonstrate an inverse correlation between 21a transcription and cenp-f expression. 21481188_1 our results demonstrate that mir-373 can regulate cell cycle progression by targeting ppp6c transcripts and promotes the growth activity of hcc cells in vitro. 21481188_2 figure 4. ppp6c is a direct target of mir-373. 21481188_3 the ppp6c 3'-utr carries one potential mir-373-binding site. 21481188_4 the direct interaction of mir-373 and ppp6c mrna was confirmed by a fluorescent reporter assay. 21481188_5 these results show that mir-373 bindirectly to the 3'-utr of the ppp6c transcript to repress gene expression. 21481188_6 these results suggest that mir-373 regulates endogenous ppp6c expression through mrna degradation. 22952885_1 these results suggest that the impdh1 and npepl1 genes are direct target of mir-19a in breast cancer, while the exogenous expression of these genes is not associated with the growth suppression of mcf-7 cells. 22952885_2 serine/threonine-protein phosphatase 2a 55 kda regulatory subunit b alpha isoform was identified as a direct targetcandidate of mir-20a, and rho gtpase-activating protein 1 , inosine-5- -monophosphate dehydrogenase 1 and probable aminopeptidase like-1 were identified as direct target candidates of mir-19a. 22952885_4 among the identified upregulated proteins, 4 proteins were shown to have mir-19a or mir-20a binding sites on the 3'-utr of their mrnas. 22952885_5 the expression levels of impdh1 and npepl1 were both increased after treatment with anti-mir-19a, while the expression levels of ppp2r2a and arhgap1 did not change . 22952885_6 taken together, our results indicate that mir-19a directly affects the post-transcriptional regulation of the impdh1 and npepl1 genes. 26844702_1 collectively, these data supported the notion that creb1 and c-met were direct downstream targets of mir-433. 14636997_1 in the present study, we describe the human and mouse rfp2 gene structure, multiple rfp2 mrna isoforms in the two species that have different 5' utrs and a human-specific antisense transcript rfp2os. 14636997_3 alignment of the complete nucleotide sequence of rfp2os mrna to the human genomic sequence shows that the rfp2os transcript is spliced and contains five "classical" exons with clear gtag borders. 24522205_1 together, these data demonstrated that mir-10a directly inhibits pik3ca expression. 21217773_1 co-transfection of the anti-mir-145 oligonucleotide with pri-mir-145 or with the mature mir-145 fully rescued luciferase activity, confirming the specificity of the suppressive pri-mir-145 effect on the fli1 3'-untranslated region. 21217773_2 the inverse correlation between hsa-mir-145 rna and ews-fli1 protein levels, and its role in ewing's sarcoma cell growth suggest that subtle variations in the balance between these two molecules may impact tumor growth and progression. 25826666_1 these results showed that pten is the target of mir-214 in osteoclast differentiation. 25826666_2 these data suggested that mir-214 regulates rankl-activated pi3k/akt signaling pathway for osteoclast differentiation by targeting pten. 26550114_1 as shown in figure 9b, the luciferase activity significantly decreased after co-transfection with psi-check-2/yap 3'-utr and mir-506 mimics in comparison with control cells, indicating that mir-506 specifically binds to the 3'-utr of yap mrna. 26550114_2 we found that yap expression at the protein levels obviously decreased in the mir-506 mimics-treatment group relative to nc group and mir-506 inhibitor group. 17891175_1 let-7c, mir-145 and mir-125b target mrnas whose proteins have been shown to be increased in prostate cancer. 19682430_1 the inhibition of mir-21 in hela cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene pdcd4. 23483249_2 these data indicated that mir-218 acts as a tumor suppressor in cervical scc. 26257582_1 aeg-1 is a potential target gene of mir-193a-3p and mir-193a-3p was negatively correlated with aeg-1 in nsclc. 20447717_1 we demonstrate that hepatocellular carcinoma is characterized by elevated levels of microrna-21 and marked reductions of pten, pdcd4, and reck expression. 20447717_2 silencing of pten and pdcd4 to prevent their induction by anti-microrna-21 treatment led to decreased apoptosis and increased invasion, while silencing of reck only led to increased invasion. 21199864_1 figure 3.regulation of arl2 expression by mir-16 at both the transcript and protein levels. 21199864_2 moreover, the arl2 protein expression was inversely correlated to mir-16 in both 293a and mcf7 cells . 21199864_3 these results demonstrate that mir-16 regulates the expression of arl2 at both the transcript and protein levels. 21199864_4 in conclusion, our results demonstrate that mir-16 directly recognizes the 3'-utr of the arl2 transcript to down-regulate its expression. 21199864_5 these results suggest that mir-16 could modulate cell migration by down-regulating genes other than arl2. 21199864_6 taken together, our data suggests that mir-16 might negatively regulate cell cycle progression from the g0/g1 phase to the s phase by silencing arl2. 24675898_1 the overexpression of mir-424 remarkably reduced luciferase activity in the c-myb wild-type reporter gene but not the mutant c-myb 3'-utr, indicating that mir-424 directly targeted the c-myb 3'-utr. 24675898_2 to assess the regulation of mir-424 in c-myb expression, the protein and mrna level of c-myb was analyzed after mir-424 overexpression. 24675898_3 c-myb protein but not mrna was obviously decreased in the presence of mir-424 mimics compared with the scrambled control in both hepg2 cells. 17604716_3 they home in on an intriguingly positioned ncrna they call hotair and make the surprising discovery that this ncrna acts in trans to regulate a hox gene cluster on a completely different chromosome, not the hox gene cluster that encodes it. 8450529_4 these include the n3-h of u23, the n7 of g26, the n7 of a26 and the phosphate between a22 and u23. 26191074_1 gja1 is a major target of mir-23a. 26191074_2 these results confirm that gja1 is a bona fide mir-23a target. 26837267_1 mir-103-mimic treatment in these cells enriched klf4 mrna but not c-myb mrna in the gw182-ips, demonstrating that mir-103 targets klf4, but not c-myb mrna in ecs . 26084420_1 in addition, ectopic upregulation of mir-138-1* could significantly inhibit the mrna expression of pdk1 in p50 b-2a13 cells . 26084420_2 however, interference of pdk1 could not affect the level of mir-138-1* in these cells , indicating that mir-138-1* regulated the pdk1 instead of vice versa. 26084420_3 these results suggested that mir-138-1* regulated the proliferation, colony formation, migration and invasion of p50 b-2a13 by targeting pdk1. 20948989_1 in silico analysis of 3'utr regions reveal a putative mir-449a targetsite in the transcript of cyclin d1 ; an oncogene involvedin directly regulating rb activity and cell cycle progression. 20948989_2 taken together, this data indicates that the cyclin d1 transcript is a direct target of mir-449a. 20948989_3 this highlights an evolutionary significance for the targetsite and corroborates the functional interaction between the cyclin d1 transcript and mir-449a. 20948989_4 this data indicates that mir-449a regulates rb phosphorylation, in part, through targeted knockdown of cyclin d1. as shown in figure 6b, knockdown of hdac1 by mir-449a or sihdac1 elevated p27 protein and reduced p-rb levels. 20948989_5 this data indicates that mir-449a also regulates rb phosphorylation though knockdown of hdac1. 26054676_1 it was verified that emmprin was a target gene of mir-485-5p by using luciferase analysis assay. 26054676_2 we identified that mir-485-5p was a tumor suppressor and negatively regulated emmprin in progression of hcc. it was verified that emmprin was a new target gene of mir-485-5p and mir-485-5p could inhibit cell proliferation and induce g1 arrest and metastasis by down-regulation of emmprin. 26847520_1 moreover, mir-203 was found to directly target the 3'un-translated regions of survivin and bmi-1 mrnas affecting proliferation and self-renewal in lscs. in this study, we identified a novel mir-203/survivin/bmi-1 axis involved in the regulation of biological properties of lscs. 26847520_3 collectively, these results suggest that mir-203 inhibits lsc proliferation and promotes apoptosis by targeting surviving via its 3'-utr. 26847520_4 mutation of the mir-203 binding sequence in the bmi-1 3'-utr abolished the suppressive effects of mir-203, confirming that bmi-1 is a direct mir-203target. 26847520_6 taken together, these data support the hypothesis that bmi-1 is a direct and functional target of mir-203 that mediates lscs stemness. 20542001_1 these results clearly demonstrated that mir-504 could negatively regulate p53 protein levels. 20542001_2 in this study, we identified mir-504 as a direct negative regulator of p53. 20542001_3 mir-504 can directly repress the p53 protein expression through its binding to the two binding sites in 3' utr of the human p53 gene, thereby negatively regulating p53 functions. 24364919_1 overexpression of mir-494 upregulated hif-1alpha expression through activating pi3k/akt pathway under both normoxia and hypoxia, and had protective effects against hypoxia-induced apoptosis in l02 cells. 21860426_1 a luciferase reporter assay in c-src-transformed cells showed that introduction of mir-542-3p significantly suppressed the expression of the ilk reporter by specifically targeting the predicted mir-542-3p binding sequences in the 3'-untranslated region of the ilk mrna . 21860426_2 western blot analysis showed that ilk protein was upregulated by c-src transformation and was significantly downregulated by the expression of mir-542-3p . 21860426_3 quantitative real-time polymerase chain reaction analyses showed that introduction of mir-542-3p substantially reduced the expression of ilk mrna and ilk protein to the same extent . 21860426_4 thus, mir-542-3p downregulates ilk protein levels by directing mrna degradation. 21860426_5 these findings demonstrate that mir-542-3p directly targets ilk, and that downregulation of mir-542-3p is associated with the upregulation of ilk in c-src-transformed cells. 21860426_6 these results suggest that ilk is able to contribute to promoting tumor growth in human cancer cells, but the growth-suppressive effect of mir-542-3p is not solely attributed to ilk downregulation. 26552447_1 the data of luciferase assay showed that mir- 29 directly targets to keap1 mrna. 26552447_2 mir- 29 directly regulates keap1. 26552447_3 by luciferase reporter assays and expression analysis of keap1 in hk mir-29 mimic or hk mir-29 inhibitor cells, we can draw a conclusion of mir-29 directly regulated keap1 expression by targeting keap1 mrna 3- utr. 26877865_1 according to in silicon analysis, p65 has two potential binding sites for mir-690 within its 3'-utr .to 26877865_2 investigate whether p65 can be directly targeted by mir-690, we engineered a luciferase reporter that has wild-type 3'-utr of p65. 26877865_3 together, these results indicate that mir-690 directly targets p65 through translational inhibition. 22689922_1 in zdesophagus and tongue, oncogenic mir-31 and mir-21 overexpression was accompanied by down-regulation of their respective tumor-suppressor target ppp2r2a andpdcd4. 22689922_2 importantly, our present study documented a correlation between overexpression of mir-21 ish signal in the inflammatory zd esophagus/tongue and loss of expression of its tumor-suppressor targetpdcd4 in the same tissues . in human tongue scc, a correlation of mir-21 overexpression with loss of its tumor-suppressor target pdcd4 and tpm1 mrna and protein expression is documented. 22689922_3 although mir-31 overexpression in zd esophagus and tongue is accompanied by down-regulation of its known tumor-suppressor targetppp2r2a , the role of ppp2r2a down-regulation has not been reported in human escc or oscc. 26163109_1 we show here that ho-1 is a target gene of mir-183 and that this mirna binds to the 3'-utr of ho-1. 26163109_2 we find that a synthetic inhibitor that binds to mir-183 decreases osteoclast differentiation and increases the expression of ho-1, while a mimic of endogenous mature mir-183 has the opposite effect. 26163109_3 moreover, the ho-1 inducers, resveratrol and piceatannol decrease the expression of mir-183, resulting in attenuated osteoclastogenesis. 26163109_5 fig. 2. ho-1 is a target of mir-183 in bmms. 26163109_6 these results indicate that mir-183 attenuates the expression of ho-1 at a posttranscriptional level by targeting its 3'-utrs. 23996750_1 ectopic expression of mir-218 in hepg2 cells resulted in suppressed cell proliferation and enhanced cell apoptosis as well as the down-regulation of bmi-1 and cdk6 mrna and protein expressions . 22200372_1 identification of mir-145 binding sites in the sox2 mrna 3- -untranslated region. 22200372_2 luciferase activity of the sox2 3'-utr sites was significantly inhibited by wt mir-145 , while luciferase activity of the mutated sox2 3'-utr sites was not inhibited, which suggested that mir-145 targeted sox2. 22200372_3 these results demonstrated that transfection of exogenous mir-145 can interfere with endogenous sox2 protein expression in human ips cells. 25044403_1 mir-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting ubqln1. 22661705_1 a novel target of microrna-29, ring1 and yy1-binding protein , negatively regulates skeletal myogenesis. 22661705_2 among them, rybp was shown to be a direct target of mir-29 through binding to its 3'-utr. 22661705_3 mir-29 directly target rybp through binding to its 3'-utr. 22661705_4 indeed, ectopic expression of mir-29 by transfection of mir-29 oligos or transfection of a pmif-mir-29 plasmid caused decreased expression of rybp at both rna and protein levels , and knockdown of mir-29 by anti-mir oligos led to increased expression of rybp. 26186482_1 pak2 is a direct target of mir-137 in melanoma cells. 26186482_2 luciferase reporter assay proves pak2 is a direct target of mir-137. 26186482_3 thus, mir-137 targets pak2 through a direct interaction with its binding site in the 3- utr. 26186482_4 taken together, these results demonstrate that pak2 is a functional target of mir-137, contributing to its role in mir-137-mediated repression of cell proliferation and induction of apoptosis in melanoma cells. 26257769_1 in this work, we focus on the post-transcriptional regulation of the brca1 gene, a major tumor suppressor and regulator of double-stranded break dna repair and show that its mrna is targeted by many members of the mir-15/107 group at a site located within the cds. 26257769_2 suppression of brca1 mrna by mir-15/107 mirnas. 26017478_1 we found that overexpression of mir-19a induced decreases in cd22 mrna and protein levels while silence of mir-19a resulted in an increased cd22 expression , indicating that mir-19a directly targeted cd22 expression. 25501507_2 luciferase assays revealed that mir-34a inhibited tgf-betar2 expression by targeting one binding site in the 3'-utr of tgf-betar2 mrna. 20820187_1 among 10 mirnas with known sequences, we have determined that mir-148a reduces the expression of cullin-associated and neddylation-dissociated 1 , a negative regulator of skp1-cullin1-f-box ubiquitin ligases, by binding to the 3'-untranslated region of cand1 mrna. 20820187_2 as expected, mir-148a transfection in lncap cells significantly reduced cand1 expression at mrna and protein levels, whereas anti-mir-148a upregulated cand1. 20820187_3 having shown mir-148a to be an androgen-inducible mirna that directly target cand1, we next questioned whether the reduction of cand1 expression accelerates lncap cell growth. 22301067_3 b expression of mir-155, il1b and il6 in pk-15 cells after stimulation with 100 ng/ml lps. 22677169_1 down-regulated mir-625 suppresses invasion and metastasis of gastric cancer by targeting ilk. 22677169_2 moreover, we identify that ilk is a direct targetgene for mir-625 and knockdown of ilk has a phenocopy of overexpression of mir-625. 22677169_3 mir-625 inhibits the protein expression of ilk by directly targeting 3'-utr of ilk. 26367487_2 these results indicate that pdcd4 is a direct target of mir-21 and that mir-21 suppresses pdcd4 by direct binding to the 3'-utr of pdcd4. 26367487_3 because stat3 has been reported as a downstream target of pdcd4, therefore, we checked the protein expression of the phosphorylated stat3 expression and found that the expression of the phosphorylated stat3 was concomitantly decreased by mir-21 inhibitor. 21475881_1 using a luciferase reporter assay, we further confirmed the translational repression activity of mir-221 on p27 by identifying the targetrecognition element within the 3'utr of p27. 21475881_2 figure 2. mir-221 directly interacts with p27 3'utr. in the present study, we showed that mir-221 target sequences within the 3'utr of p27 and is capable of arresting the translation of luciferase from a luciferase, p27-3'utr gene fusion in transfected u251 glioblastoma cells. 21475881_3 this in vitro evidence, in conjunction with our finding that p27 protein levels decrease in concert with increased mir-221 expression in human gliomas, supports the conclusion that progressive increases in mir-221 expression lead to the increased translational repression of p27, thus increasing the malignancy of gliomas. 26052251_1 thus, we speculated that dlx6-as1 was an oncogene and knockdown of dlx6-as1 decreased dlx6 expression. 26052251_2 to test it, we investigated the changes of dlx6 mrna and protein levels after a549 and h1650 cells were transfected with sirna targeting lncrna dlx6-as1 , negative control blank. 24682933_1 silencing mir-200c expression significantly induced cell apoptosis,the effects of silencing mir-200c expression were associated with upregulation of pten protein and p53 ser phosphorylation levels in hct-116 cells and pten protein expression in ht-29 cells. 19378336_6 in addition, significant decreases in cell growth were observed after transfection of 3 mirnas and si-krt7 in kk47, suggesting that mir-30-3p, mir-133a and mir-199a* may have a tumor suppressive function through the mechanism underlying transcriptional repression of krt7. 25878394_1 hnf4g is a downstream target of mir-34a in bladder cancer. 25878394_2 there results suggest that mir-34a can directly target hnf4g and modulate its expression. 18056640_1 to verify that the putative mir-125b binding site in the 3'-utr of bak1 is responsible for regulation by mir-125b, we cloned this 3'-utr into the prim reporter-luciferase vector. 18056640_2 examination of the antisense sequences of this 3'-utr did not identify a mir-125b binding site, and thus the antisense-inserted vector was used as a negative control. the sense- or antisense-inserted reporter vector was cotransfected with mir-125bm into mir-125b-negative du145 cells. 18056640_5 6e, mir-125bm transfection did not alter luciferase activity in du145 cells cotransfected with either pmir-report luciferase vector or bak1 3'-utr antisense-inserted vector. 18056640_7 these results indicate that the 3'-utr of bak1 transcript is a mir-125b target. 25107369_1 the exogenous mir-34a regulates tubular apoptosis by modulating the expression of the anti-apoptotic protein bcl-2. 18834855_1 mir-34a expression was markedly reduced in p53-null pc3 cells and p53-mutated du145 cells compared with lncap cells expressing wild-type p53. in pc3 cell, ectopic expression of mir-34a decreased the sirt1 mrna and protein levels as well as protein levels of known direct target genes. 18834855_2 reporter assays revealed that mir-34a-induced sirt1 inhibition occurred at the transcriptional but not post-transcriptional level despite the presence of a potential mir-34a binding site within its 3'-utr. 18834855_3 ectopic mir-34a expression resulted in cell cycle arrest and growth inhibition and attenuated chemoresistance to anticancer drug camptothecin by inducing apoptosis, suggesting a potential role of mir-34a for the treatment of p53-defective prostate cancer. 18403645_4 second, the constructions of hmga2 with and without 3-utr in these cell lines using retroviral pbabe vectors will allow us to further characterize the specificity for let-7 repression of hmga2a in the presence and absence of let-7 lcs. 25683382_1 mir200c directly binds to irs1 through the seed sequences in irs1 3'-utr. 25683382_2 artificial overexpression of mir200c significantly downregulated the mrna and protein levels of irs1, together with decreased cell proliferation and increased cell death of pc3 and du145 cells. 26328011_2 we used targetscan 6.2 , a widely used mirna target prediction website,lmo3 was found to be a potential target of mir-630. 26328011_4 moreover, qrt-pcr and western blotting confirmed that mir-630 suppressed the expression of lmo3 in nci-h23 cells . 26328011_5 these data suggested that lmo3 was a target of mir-630 in nsclc cells. 21494432_2 it was shown that the amount of big-h3 protein was decreased after over-expression of mir-21 , suggesting that mir-21 negatively regulates endogenous big-h3 protein expression through translational repression mechanism. 21494432_3 these data, taken together, indicate that although other possible mediators existed, one possible downstream target of mir-21 that played a role in cell proliferation and radiation-induced apoptosis was big-h3. in conclusion, we identified that the mir-21 could directly targettumor suppressor gene big-h3, which may also play an important role in radiation-induced carcinogenesis. 22678116_1 together these results show that mir-21 regulates expression of csf-1 in breast cancer cells. 22678116_3 these results indicated that mir-21 regulated expression of csf-1 via pten. 22678116_4 these results suggest that the action of mir-21 on expression of csf-1 is mediated by pten. 25270723_1 it has been proven that pten was the direct target of mir-494 in other cells . 25270723_2 considering the tissue-specific and developmental stage-specific manner of mirnas, we investigate the relationship of pten and mir-494 in crc cell lines. 25270723_3 the expression of pten at mrna and protein level was significantly downregulated after overexpression of mir-494 in sw480 cell line. 25270723_4 conversely, the expression of pten was significantly upregulated after knockdown mir-494 expression in sw620 cell line. 25270723_5 taken together, our results suggest that mir-494 negatively regulates the expression of its potential target gene pten in crc cell lines and tissues. 26191328_1 these results indicate that mir-144 might induce a549 cell apoptosis by targeting zeb1 protein. 26191328_2 these results suggest that mir-144 regulates the expression of zeb1 by interacting with its 3'-utr region. 25480402_1 the qrt-pcr assays showed significant downregulation of mir-494 and upregulation of clptm1l mrna , both of which were significantly associated with lymph node metastases . 25480402_3 the results also showed that clptm1l was a target of mir-494.