miR-449a inhibits proliferation and invasion by regulating ADAM10 in hepatocellular carcinoma

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a crucial role in tumor procession. It has been demonstrated that miR-449a expression was downregulated and served as tumor suppressor in many types of tumor. However, the biological function and molecular mechanism of miR-449a in hepatocellular carcinoma (HCC) still remains largely unknown. Therefore, the aims of this study were to investigate biological role and molecular mechanism of miR-449a in HCC by a serial of molecular experiments. Here, we demonstrated that miR-449a expression was downregulated in HCC tissues and cell lines compared with the adjacent nontumor tissues and normal hepatic cell line. Ectopic expression of miR-449a suppressed HCC cell proliferation, colony formation, migration and invasion. Moreover, A Disintegrin And Metalloproteinases 10 (ADAM10) was identified as a direct target gene of miR-449a in HCC cell. ADAM10 expression was upregulated in HCC tissues and cell lines, and was negatively correlated with the expression level of miR-449a in HCC tissues. Interesting, overexpression of ADAM10 attenuated the inhibition effect of miR-449a-mediated HCC cell proliferation, colony formation, migration and invasion. These results suggested that miR-449a might function as a tumor suppressor miRNA, at least in part, through regulating ADAM10 expression in HCC.