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

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

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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 dis-ease.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.

HBV G1896A mutationHepatocellular carcinoma(HCC)ProliferationApoptosisERK/MAPK

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

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Institute of Medical and Health Science,Hebei Medical University,Shijiazhuang,050017,China

Department of Pathogen Biology,Hebei Medical University,Shijiazhuang,050017,China

Department of Gastroenterology and Hepatology,The Fourth Hospital of Hebei Medical University,Shijiazhuang,050000,China

State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega Science,Chinese Academy of Sciences,Wuhan,430207,China

Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230026,China

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S&T Program of HebeiNatural Science Foundation of Hebei Province,ChinaNatural Science Foundation of Hebei Province,ChinaScience and Technology Project of Hebei Education DepartmentScience and Technology Project of Hebei Education DepartmentHebei Medical Science Research ProjectChinese Medicine Research Program of Hebei Province

20372601DH2020206352C2021206004QN2018150QN2020268202209732021119

2023

10.1016/j.virs.2023.06.004

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.38(5)
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