406944

MIR153-1

The overall goal of the present study was to find and validate unidentified miRNAs that regulate epithelial-mesenchymal transition (EMT) and proliferation in ovarian cancer. Furthermore, we demonstrate that the high expression of miR-153 in human epithelial ovarian cancer (EOC) is associated with better survival. The mean expression level of miR-153 in ovarian cancer was significantly lower than in the adjacent carcinoma tissue. In the present study, we report that miR-153 are negative regulators of SET7 and ZEB2, miR-153 regulates SET7/ZEB2 expression and promotes SET7/ZEB2 mRNA degradation. Further, confirmed by reporter assays, SET7/ZEB2 are downstream targets of miR-153 directly bound to the 3' untranslated region (3'-UTR). Clone formation and wound-healing assay as well as Transwell assay proved that silencing of SET7 or ZEB2 partially abolished the enhancement of cell proliferation and invasion induced by downregulated miR-153. SET7 and ZEB2 are negatively correlated with miR-153 expression in human ovarian cancer and indicated a worse survival. Considering the role of SET7 and ZEB2 in EOC, it is important to clarify how the expression of SET7 and ZEB2 are regulated. Based on our results miR-153 inhibits proliferation and suppresses EMT and the invasive potential of ovarian cancer cells through downregulation of SET7 and ZEB2, supporting the pursuit of miR-153 as a potential target for ovarian cancer intervention.

epithelial-to-mesenchymal transition (EMT) has been implicated as a dynamic cellular process in embryonic development and invasion of human cancers. Snail1 is a critical convergence hub in EMT regulation which transcriptionally represses E-cadherin expression. Currently, published data indicate that upregulation of Snail is mainly due to transcriptional activation and regulation of protein stability and cellular location. However, whether there is an alternative regulatory mechanism remains unclear. Our study showed that the expression of miR-153 was noticeably downregulated in hepatocellular carcinoma (HCC) cell lines and tissues, compared with normal liver epithelial cells (NLCs) and matched adjacent normal HCC tissues. Ectopic expression of miR-153 inhibited the migration and invasion ability of HCC cells, while suppression of miR-153 rescued this inhibitory effect. In addition, upregulation of miR-153 in HCC cells resulted in a decrease in epithelial markers, E-cadherin and alpha-catenin, and an increase in mesenchymal markers, N-cadherin and vimentin, and vice versa. Moreover, we demonstrated that miR-153 downregulated Snail expression by directly targeting the 3'-untranslated region (3'UTR) of Snail. Taken together, our results suggest that miR-153 plays a critical role in suppressing EMT and HCC progression by direct suppression of Snail expression.