MicroRNA-29 family functions as a tumor suppressor by targeting RPS15A and regulating cell cycle in hepatocellular carcinoma.

Growing evidence shows that miRNA plays an important role in the development and progression of cancer. In this study, we found that the expression levels of miR-29 family were dramatically decreased in hepatocellular carcinoma (HCC) cell lines and clinical tissues. Then, we demonstrated that ectopic expression of miR-29 family could significantly suppress cell proliferation and induce apoptosis in HCC cells. Luciferase assay together with western blot assay confirmed that miR-29 family bound directly to the 3'-untranslated region (3'-UTR) of RPS15A and reduced the expression of RPS15A. In addition, the cell cycle related gene including cyclinA, cyclin D1 and p21 were also down-regulated when increased the expression of miR-29 family, which is similar as silencing RPS15A expression. Moreover, co-transfection of miR-29 mimics with 3'UTR-deleted RPS15A could rescue the expressions of cyclin A and cyclin D1 while down-regulate the p21 expression. In conclusion, miR-29 family functions as a novel tumor suppressor in HCC by regulate cell growth and cell cycle through binding to RPS15A 3'UTR. These findings may be utilized in developing novel therapeutic tools for HCC.