CircRNA circARNT2 Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting the miR-155-5p/PDK1 Axis

Abstract

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.