• Bangxiang Xie, Qian Hao, Xiang Zhou, and Dexi Chen.
• Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
• Chin. Med. J. 2022 Jul 20; 135 (14): 172817331728-1733.

BackgroundThe 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.MethodsTo 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.ResultsHBx 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.ConclusionHBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

25 keywords...

hide…