406958

MIR182

MIRN182|miRNA182;microRNA 182;MIR182;microRNA 182

hsa-mir-182

7q32.2

ncRNA

microRNAs (miRNAs) constitute a class of noncoding RNAs that post-transcriptionally regulate gene expression. Recent evidence indicates that many miRNAs function as oncogenes or tumor suppressors by negatively regulating their target genes. In our previous study, using miRNA microarray analysis, we found that miRNA-182 (miR-182) was significantly downregulated in human gastric adenocarcinoma tissue samples. Here, we confirmed the downregulation of miR-182 in a larger sample of gastric tissue samples. Overexpression of miR-182 suppressed the proliferation and colony formation of gastric cancer cells. An oncogene, encoding cAMP-responsive element binding protein 1 (CREB1), serves as a direct target gene of miR-182. A fluorescent reporter assay confirmed that miR-182 binds specifically to the predicted site of the CREB1 mRNA 3-UTR. When miR-182 was overexpressed in gastric cancer cell lines, both the mRNA and protein levels of CREB1 were depressed. Furthermore, CREB1 was present at a high level in human gastric adenocarcinoma tissues, and this was inversely correlated with miR-182 expression. Ectopic expression of CREB1 overcame the suppressive phenotypes of gastric cancer cells caused by miR-182. These results indicate that miR-182 targets the CREB1 gene and suppresses gastric adenocarcinoma cell growth, suggesting that miR-182 shows tumor-suppressive activity in human gastric cancer.

microRNAs (miRNAs) are endogenous small non-coding RNAs that play central roles in diverse pathological processes. In this study, we investigated the effect of microRNA-182 (miR-182) on the development of posterior uveal melanomas. Initially, we demonstrated that miR-182 expression was dependent on p53 induction in uveal melanoma cells. Interestingly, transient transfection of miR-182 into cultured uveal melanoma cells led to a significant decrease in cell growth, migration, and invasiveness. Cells transfected with miR-182 demonstrated cell cycle G1 arrest and increased apoptotic activity. Using bioinformatics, we identified three potential targets of miR-182, namely MITF, BCL2 and cyclin D2. miR-182 was shown to have activity on mRNA expression by targeting the 3 untranslated region of MITF, BCL2 and cyclin D2. Subsequent Western blot analysis confirmed the downregulation of MITF, BCL2 and cyclin D2 protein expression. The expression of oncogene c-Met and its downstream Akt and ERK1/2 pathways was also downregulated by miR-182. Concordant with the findings that miR-182 was decreased in uveal melanoma tissue samples, overexpression of miR-182 also suppressed the in vivo growth of uveal melanoma cells. 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.