MiR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73.

Abstract

Aberrant expression of miRNAs has been documented to play critical roles in the development and progression of hepatocellular carcinoma (HCC). However, the expression pattern, functional roles and regulatory mechanism of miR-493-5p in HCC have not been addressed. Herein, we found that miR-493-5p was significantly downregulated in HCC tissues and was tightly associated with tumor size, tumor differentiation grade and TNM stage of HCC patients. Overexpression of miR-493-5p inhibited HCC cell proliferation, arrested cell cycle in G0/G1 phase and induced cell apoptosis. Bioinformatical analysis and luciferase reporter assay further proved that Golgiprotein73 (GP73), an oncogene which was generally overexpressed in HCC, acted as a novel target of miR-493-5p. MiR-493-5p could inhibit GP73 both mRNA and protein expression. Moreover, overexpression of GP73 could reverse the inhibitory effects of miR-493-5p mediated HCC cell proliferation. In addition, upregulated GP73 in HCC tissues was inversely correlated with the miR-493-5p expression levels in the HCC tissues. Collectively, our present study demonstrates that miR-493-5p is downregulated in HCC and it can suppress the proliferation of HCC cells, partly at least, via directly targeting GP73. Besides, this study provides a novel insight into the mechanism of hepatocarcinogenesis and a promising blueprint for miR-493-5p-GP73 axis-oriented treatment of HCC.