MicroRNA (miR)-153 Inhibits Epithelial-Mensenchymal Transition in Hepatocellular Carcinoma

Abstract: Epithelial-to-mesenchymal transition (EMT) has been implicated in dynamic cellular processes in embryonic development and invasion of human cancers. Snail1 is a critical convergence hub in EMT regulation which transcriptionally represses E-cadherin expression. Currently, upregulation of Snail is mainly due to dual regulation by protein stability and cellular location, and partially by transcriptional activation. However, whether an alternative regulatory mechanism exists, remains unclear. Herein, we report the functional involvement of miR-153 in EMT and its regulation of Snail in HCC cells. We demonstrated that expression of miR-153 is noticeably downregulated in HCC cell lines and tissues, compared with normal liver epithelial cells (NLC) and matched adjacent normal HCC tissues. Ectopic expression of miR-153 inhibited the migration and invasion of HCC cells, while suppression of miR-153 prevented this effect. In addition, upregulation of miR-153 in HCC cells resulted in downregulation of epithelial markers E-cadherin and -catenin, and upregulation of mesenchymal markers N-cadherin, Vimentin as well as Fibronectin, and vice versa. Moreover, we demonstrated that miR-153 downregulated Snail expression by directly targeting the 3’-untranslated region (3’-UTR) of Snail mRNA. Taken together, our results suggest that miR-153 plays a critical role in suppressing EMT and HCC progression. We also present a novel mechanism of microRNA-mediated direct suppression of Snail expression in cancer cells.