Research Papers:

Hepatitis B virus X protein inhibits apoptosis by modulating endoplasmic reticulum stress response

Jia Li, Jiang He, Yongming Fu, Xingwang Hu, Lun-Quan Sun, Yan Huang and Xuegong Fan _

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Oncotarget. 2017; 8:96027-96034. https://doi.org/10.18632/oncotarget.21630

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Jia Li1,4, Jiang He2,3, Yongming Fu1, Xingwang Hu1, Lun-Quan Sun2,3, Yan Huang1 and Xuegong Fan1

1Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, China

2Center for Molecular Medicine, Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha 410078, China

3Key Laboratory of Molecular Radiation Oncology, Changsha 410008, China

4Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, China

Correspondence to:

Xuegong Fan, email: [email protected]

Yan Huang, email: [email protected]

Keywords: HBV; HBx; hepatocellular carcinoma; ER stress; apoptosis

Received: March 15, 2017     Accepted: August 26, 2017     Published: October 06, 2017


Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of the four open reading frames of HBV, and is well known as an important coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis. However, its role in keeping cells from apoptosis to promote HCC proliferation remains controversial. Here, we used HBx expressing HCC cells as a model, to investigate the mechanism of HBx-mediated cellular response to endoplasmic reticulum (ER) stress. We found that HBx protein was localized in ER lumen and interacted with GRP78 directly. This interaction resulted in suppression of eIF2α phosphorylation, inhibited expression of ATF4/CHOP/Bcl-2, and reduced cleavage of poly ADP-ribose polymerase (PARP) and level of γH2AX, thus preventing HCC cells from cell death and negatively regulating DNA repair. This study reveals a novel mechanism of the HBx-mediated oncogenesis and provides a basis for potential HBx-targeted therapeutic intervention of HCC.

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