Oncotarget

Research Papers:

LHBs can elevate the expression of MDR1 through HIF-1α in patients with CHB infection: a comparative proteomic study

Shiying Li, Yixuan Yang, Xiangchun Ding, Min Yang, Sha She, Hong Peng, Xiaoming Xu, Xiaoping Ran, Sanglin Li, Peng Hu, Huaidong Hu, Dazhi Zhang _ and Hong Ren

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Oncotarget. 2017; 8:4549-4562. https://doi.org/10.18632/oncotarget.13941

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Abstract

Shiying Li1, Yixuan Yang1, Xiangchun Ding2, Min Yang1, Sha She1, Hong Peng1, Xiaoming Xu1, Xiaoping Ran1, Sanglin Li1, Peng Hu1, Huaidong Hu1, Dazhi Zhang1, Hong Ren1

1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

2Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, PR China

Correspondence to:

Dazhi Zhang, email: zhangdazhi_1014@163.com

Keywords: LHBs, MDR1, HIF-1α, iTRAQ, proteomics

Received: May 26, 2016     Accepted: December 05, 2016     Published: December 15, 2016

ABSTRACT

Background and Aims: Hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). To gain a better understanding of the pathogenesis of HBV infection, this study aimed to investigate the differentially expressed proteins (DEPs) in liver tissues from patients with chronic hepatitis B (CHB) infection.

Results: Seventy-one DEPs were identified. Overexpression of multi-drug resistance protein 1 (MDR1) was validated by RT-qPCR and western blot analyses. Moreover, its expression was increased at both the mRNA and protein levels in response to overexpression of HBV large surface protein (LHBs). Furthermore, screening of transcription factors suggested the possible involvement of hypoxia-inducible factor 1α (HIF-1α) in the interaction between LHBs and MDR1. The function of HIF-1α in the MDR1 activation was confirmed by EMSA and reporter gene analyses.

Materials And Methods: Liver samples from CHB patients and controls without HBV infection were collected and subjected to isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometric analysis.

Conclusions: These results imply that LHBs, in association with HIF-1α, induces MDR1 overexpression, which may contribute to the pathogenic changes in CHB infection.


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