A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines

作者：Shi, Ying; Wang, Junwei; Wang, Yuhe; Wang, Anna; Guo, Hongliang; Wei, Feili; Mehta, Sanjay R.; Espitia, Stephen; Smith, Davey M.; Liu, Longgen^*; Zhang, Yulin^*; Chen, Dexi^*

来源：Cancer Letters, 2016, 371(2): 285-291.

DOI：10.1016/j.canlet.2015.12.008

• Hepatitis B virus
• Mutation
• Hepatocellular carcinoma

Hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC) represents a major health problem worldwide. HBV X (HBx) protein is the most common open reading frame that may undergo mutations, resulting in the development of HCC. This study aimed to determine specific HBx mutations that differentiate the central- and para-tumor tissues, and identify their association with HCC development. HBx gene from HCC tumor and para-tumor tissues of 47 HCC patients was amplified, sequenced and statistically analyzed. A novel combination of 2 mutations at residues 10 and 144 was identified which might play a significant role in HCC development. Expression vectors carrying HBx with the specific mutations were constructed and transfected into HepG2 and p53-null HepG2 cells. Compared to wild type (WT) and single mutation of HBx at residue 10 or 144, the 10/144 double mutations strongly up regulated p21 expression and prolonged G1/S transition in WT- and p53-null HepG2 cells. Apoptosis was also inhibited by HBx harboring 10/44 double-mutation. Binding of 10/144 double-mutant HBx to p53 was lower than WT HBx. Conclusively, the 10/144 double mutation of HBx might play a crucial role in HCC formation.

• 出版日期2016
• 单位首都医科大学