MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1.

Abstract

Deregulation of microRNAs (miRs) has been observed in a variety of types of human cancer. Previously, miR-30a-5p has been demonstrated to exhibit a suppressive role in hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. The present study aimed to elucidate the regulatory mechanism of miR-30a-5p in proliferation and invasion of HCC cells. Quantitative reverse transcription polymerase and western blotting were used to examine mRNA and protein expression of Forkhead box A1 (FOXA1). MTT and Transwell assays were performed to examine proliferation and invasion. Luciferase reporter assay was used to determine the association between miR-30a-5p and FOXA1. The data indicated that miR-30a-5p was significantly downregulated in HCC tissues compared with normal liver tissues. Furthermore, the level of miR-30a-5p was lower in HCC tissues with higher histological grade and advanced tumor stage compared with tissues with lower histological grade and tumor stage. Additionally, restoration of miR-30a-5p expression decreased the proliferation and invasion of HCC HepG2 and SMMC-7721 cells. FOXA1, a novel oncogene in HCC, was further identified as a target of miR-30a-5p. Furthermore, high expression of miR-30a-5p suppressed mRNA and protein expression of FOXA1, while overexpression of FOXA1 reversed the suppressive effect of miR-30a-5p on proliferation and invasion of HepG2 and SMMC-7721 cells. FOXA1 was markedly upregulated in HCC tissues compared with normal liver tissues, and its level was higher in HCC tissues with higher histological grade and advanced tumor stage. In addition, it was found that overexpression of miR-30a-5p significantly suppressed the tumor growth of HCC cells in nude mice. Taken together, the present study supports that miR-30a-5p inhibits the proliferation, invasion, and tumor growth of HCC cells, partly at least, by inhibition of FOXA1 expression, and therefore suggests that miR-30a-5p may serve as a potential candidate for HCC therapy.