MiR-126 inhibits cell proliferation and induces cell apoptosis of hepatocellular carcinoma cells partially by targeting Sox2.

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death globally. MicroRNAs (miRNAs) represent a new cohort of gene regulators. Currently, a large number of miRNAs have been reported to be associated with the initiation and maintenance of HCC. Through evaluating the relative concentrations of HCC-associated circulating miRNAs, underexpression of miR-126 has been identified in the blood of HCC patients. However, the exact function of miR-126 on HCC cellular biology progression and relative mechanisms were unclear. In this paper, we explored the function of miR-126 on HCC cells through exogenously transfecting HCC cells with miR-126 mimic. Restored miR-126 expression inhibited cell proliferation, arrest cell cycle progression, and induced cell apoptosis of HepG2 HCC cells. Moreover, to explore the mechanism of miR-126-mediated tumor suppression, we searched the putative targets of miR-126 using prediction program. Surprisingly, we found that sex-determining region Y-box 2 (Sox2) was a putative target gene of miR-126. Further luciferase assays, mRNA and protein assays consistently validated the target role of Sox2. Through restoring the expression of Sox2 in miR-126-transfected HepG2 cells, we found that overexpression of Sox2 could partially abrogate the miR-126-mediated suppression of cell growth. Thus, our data identified miR-126 as a tumor suppressor in HCC through, at least partially by targeting Sox2. This may provide novel diagnostic and therapeutic options for human HCC in future.