HBV precore G1896A mutation promotes growth of hepatocellular carcinoma cells by activating ERK/MAPK pathway  

作　　者：Baoxin Zhao Hongxiu Qiao Yan Zhao Zhiyun Gao Weijie Wang Yan Cui Jian Li Zhanjun Guo Xia Chuai Sandra Chiu 

机构地区：[1]Institute of Medical and Health Science,Hebei Medical University,Shijiazhuang,050017,China [2]Department of Pathogen Biology,Hebei Medical University,Shijiazhuang,050017,China [3]Department of Gastroenterology and Hepatology,The Fourth Hospital of Hebei Medical University,Shijiazhuang,050000,China [4]State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega Science,Chinese Academy of Sciences,Wuhan,430207,China [5]Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230026,China

出　　处：《Virologica Sinica》2023年第5期680-689,共10页中国病毒学（英文版）

基　　金：This work was supported by the S&T Program of Hebei(20372601D);the Natural Science Foundation of Hebei Province,China(H2020206352,C2021206004);the Science and Technology Project of Hebei Education Department(QN2018150,QN2020268),Hebei Medical Science Research Project(20220973);Chinese Medicine Research Program of Hebei Province(2021119).

摘　　要：Chronic hepatitis B virus(HBV)infection is one of the leading causes of hepatocellular carcinoma(HCC).The HBV genome is prone to mutate and several variants are closely related to the malignant transformation of liver disease.G1896A mutation(G to A mutation at nucleotide 1896)is one of the most frequently observed mutations in the precore region of HBV,which prevents HBeAg expression and is strongly associated with HCC.However,the mechanisms by which this mutation causes HCC are unclear.Here,we explored the function and molecular mechanisms of the G1896A mutation during HBV-associated HCC.G1896A mutation remarkably enhanced the HBV replication in vitro.Moreover,it increased tumor formation and inhibited apoptosis of hepatoma cells,and decreased the sensitivity of HCC to sorafenib.Mechanistically,the G1896A mutation could activate ERK/MAPK pathway to enhanced sorafenib resistance in HCC cells and augmented cell survival and growth.Collectively,our study demonstrates for the first time that the G1896A mutation has a dual regulatory role in exacerbating HCC severity and sheds some light on the treatment of G1896A mutation-associated HCC patients.

关 键 词：HBV G1896A mutation Hepatocellular carcinoma(HCC) Proliferation Apoptosis ERK/MAPK 

分 类 号：R373.1[医药卫生—病原生物学]