MiR-146a suppresses hepatocellular carcinoma by downregulating TRAF6

Am J Cancer Res. 2016 Nov 1;6(11):2502-2513. eCollection 2016.

Abstract

MicroRNAs have been proven to play important roles in many biological processes such as cellular growth and differentiation, apoptosis, and modulation of host response to viral infection. In the present study, we find that the expression of miR-146a was decreased in hepatocellular carcinoma (HCC) tissues compared with corresponding adjacent tissues, and the expression level in HCC cell lines was lower than in a normal liver cell. Over-expression suppressed the proliferation and invasion of HCC cells. In addition, luciferase reporter assays and western blotting confirmed that miR-146a directly target TRAF6 which attenuated the effect of miR-146a on cell proliferation and invasion in HepG2 and SMMC7721 cells. Meanwhile, lentivirus-mediated increased expression of miR146a repressed tumor formation in nude mice. Taken together, our findings demonstrate that miR-146a suppresses HCC by down-regulating TRAF6. We also discovered that miR-146a may represent a novel potential candidate of the HCC carcinoma diagnostic marker in the long term.

Keywords: Hepatocellular carcinoma; TRAF6; invasion; miR-146a; proliferation; xenografted tumor.