中国病毒学2023，Vol.38Issue(5) ：680-689.DOI:10.1016/j.virs.2023.06.004

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

Baoxin Zhao Hongxiu Qiao Yan Zhao Zhiyun Gao Weijie Wang Yan Cui Jian Li Zhanjun Guo Xia Chuai Sandra Chiu
中国病毒学2023，Vol.38Issue(5) ：680-689.DOI:10.1016/j.virs.2023.06.004
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HBV precore G1896A mutation promotes growth of hepatocellular carcinoma cells by activating ERK/MAPK pathway

Baoxin Zhao 1Hongxiu Qiao 1Yan Zhao 1Zhiyun Gao 1Weijie Wang 1Yan Cui 1Jian Li 2Zhanjun Guo 3Xia Chuai 4Sandra Chiu5
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作者信息

  • 1. Institute of Medical and Health Science,Hebei Medical University,Shijiazhuang,050017,China;Department of Pathogen Biology,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. Department of Pathogen Biology,Hebei Medical University,Shijiazhuang,050017,China;State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega Science,Chinese Academy of Sciences,Wuhan,430207,China
  • 5. Institute of Medical and Health Science,Hebei Medical University,Shijiazhuang,050017,China;Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230026,China
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Abstract

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.

Key words

HBV G1896A mutation/Hepatocellular carcinoma(HCC)/Proliferation/Apoptosis/ERK/MAPK

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基金项目

S&T Program of Hebei(20372601D)

Natural Science Foundation of Hebei Province,China(H2020206352)

Natural Science Foundation of Hebei Province,China(C2021206004)

Science and Technology Project of Hebei Education Department(QN2018150)

Science and Technology Project of Hebei Education Department(QN2020268)

Hebei Medical Science Research Project(20220973)

Chinese Medicine Research Program of Hebei Province(2021119)

出版年

2023
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
参考文献量50
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