HBV-encoded circRNA-5 promotes hepatocellular carcinoma progression by regulating the miR-9-3p/Hippo signaling axis

Chronic hepatitis B virus (HBV) infection is regarded as one of the most serious infectious diseases and a significant global public health concern. Although the neonatal vaccine has been effective in impeding the transmission of HBV, tens of millions of HBV patients are still vulnerable to liver disease and even hepatocellular carcinoma (HCC). In this research, we demonstrated that HBV-encoded circRNA, designated as HBV-circRNA-5, was involved in the tumorigenesis of HCC. Overexpression of HBV-circRNA-5 promoted HCC cell proliferation and metastasis <i>in vitro</i> and promoted HCC tumor growth <i>in vivo</i>. Mechanistically, HBV-circRNA-5 bound to miR-9-3p selectively and resulted in the upregulation of YAP/TAZ expression, which consequently stimulated the proliferation of HCC. Overall, we provide new insight into understanding carcinogenesis and the progression of HBV-mediated HCC, as well as clarify a new cellular mechanism by which HBV promotes HCC progression through the HBV-circRNA-5/miR-9-3p/Hippo network.IMPORTANCEHBV-mediated cirrhosis is considered a significant predisposing danger among HCC individuals despite the increasing incidence of HCC due to noninfectious factors. However, it is still unclear what molecular mechanisms underlie the emergence of HBV-mediated HCC. This study identifies HBV-encoded circular RNA HBV-circRNA-5 as a critical driver of HCC progression, with the capacity to promote HCC formation through the miR-9-3p/Hippo pathway. In summary, our study developed novel insights into understanding the molecular mechanism behind HBV-related HCC development and proposed a potential target for HCC treatment.