Background::The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes.Methods::To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299.Results::HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA, consequently leading to restricted apoptosis and augmented proliferation of HCC cells. Conclusion::HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.

TAp63;hepatitis B virus X;Apoptosis;Proliferation;Liver cancer

Xie Bangxiang;Hao Qian;Zhou Xiang;Chen Dexi

Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China;Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing 100069, China;Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China;Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

中华医学杂志（英文版）

[1]Xie Bangxiang;Hao Qian;Zhou Xiang;Chen Dexi-.Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma)[J].中华医学杂志（英文版）,2022(14):1728-1733

transactivating,immunoprecipitated,Np63

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