Hepatitis B virus X promotes tumorigenesis of hepatocellular carcinoma through HIPPO signaling pathway in mice

Abstract

Objective To explore the changes in HIPPO signaling pathway in mouse liver tissues expressing hepatitis B virus X protein (HBx) and explore the mechanism of HBx for causing hepatocellular carcinoma (HCC). Methods Immortalized murine liver progenitor cells transfected with HBx gene were injected in mice via the hepatic portal vein. At 30, 90, 180, and 360 d after the cell injection, the liver tissues of the mice were sampled to examine HBx expression using real-time PCR, Western blotting and immunohistochemistry; the expression levels of the key factors in the HIPPO signaling pathway (MST1, YAP1, p-MST1, and p-YAP1) were detected using real-time PCR and Western blotting. Results We successfully established a mouse model with HBx expression in the liver tissues. The results of both real-time PCR and Western blotting showed that the expression levels of MST1 and p-YAP1 were down-regulated and YAP1 and p-MST1 were up-regulated in the liver tissues of the mouse model, and such changes persisted till the occurrence of HCC. Conclusion HBx causes HCC in mice possibly by persistently affecting HIPPO signaling pathway.

Keywords

• hepatitis b virus x protein
• animal models
• hepatocellular carcinoma
• hippo signaling pathway