Circ_0073228 serves as a competitive endogenous RNA to facilitate proliferation and inhibit apoptosis of hepatocellular carcinoma cells by the miR-139-5p/DNASE2 axis.

Abstract

Hepatocellular carcinoma (HCC) is a common malignancy and has extremely poor prognosis and outcome. Homo sapiens deoxyribonuclease II (DNASE2) has been reported to participate in HCC progression. Here, the role of DNASE2 in HCC cells and the putative upstream circRNA that mediates DNASE2 expression was investigated. The expression of RNAs in liver hepatocellular carcinoma (LIHC) samples was analyzed by bioinformatic analysis. The proliferation, apoptosis, migration, invasion, and gene expression in HCC cells were investigated using CCK-8, colony formation, flow cytometry analysis, wound healing, transwell, western blotting, and RT-qPCR. The binding relationship among circ_0073228, miR-139-5p and DNASE2 was measured by RNA pulldown and luciferase reporter assays. DNASE2 knockdown inhibited proliferation and promoted apoptosis of HCC cells while DNASE2 overexpression exerted an opposite results. MiR-139-5p targeted DNASE2 and suppressed its expression. Overexpression of miR-139-5p inhibited malignant phenotypes of HCC cells. RPS23-derived circ_0073228, which bound to miR-139-5p, was found upregulated in HCC cells. Inhibition of miR-139-5p or overexpression of DNASE2 counteracted the inhibitory effects of circ_0073228 knockdown on HCC cell progression. Circ_0073228 serves as an oncogne to facilitate growth and inhibit apoptosis of HCC cells by regulating the miR-139-5p/DNASE2 axis.