TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p

Hepatocellular carcinoma (HCC) is among the most common malignancies and has an unfavorable prognosis. The hepatitis B virus-encoded X (HBx) protein is closely associated with hepatocarcinogenesis. Sorafenib is a unique targeted oral kinase inhibitor for advanced HCC. Long noncoding RNAs (lncRNAs) mediate HCC progression and therapeutic resistance by acting as competing endogenous RNAs (ceRNAs). However, the ceRNA regulatory mechanisms underlying sorafenib resistance in HBx-associated HCC remain largely unknown. In this study, we found that lncRNA TRERNA1 upregulation by HBx not only promoted HCC cell proliferation by regulating the cell cycle in vitro and in vivo but also correlated positively with poor prognosis in HCC. Importantly, TRERNA1 enhanced sorafenib resistance in HCC cells. RNA sequencing (RNA-seq) analysis indicated that NRAS is…