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01-08-2016 | Original Article

Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response

Authors: Lingbao Kong, Shanshan Li, Xilan Yu, Xiaonan Fang, Ahui Xu, Mingjie Huang, Xiaoyu Wu, Yunli Guo, Fenglin Guo, Jin Xu

Published in: Archives of Virology | Issue 8/2016

Abstract

Oxidative stress induces the activation of signal transducer and activator of transcription 3 (STAT3), which plays an important role in hepatocellular carcinoma (HCC). We have previously reported that hepatitis C virus (HCV) and its protein NS4B induce the production of reactive oxygen species (ROS) via the endoplasmic reticulum overload response (EOR) in human hepatocytes. Here, we found that NS4B and HCV induce STAT3 activation and stimulate the expression of cancer-related STAT3 target genes, including VEGF, c-myc, MMP-9 and Mcl-1, by EOR in human hepatocytes. Moreover, the cancer-related STAT3 pathway activated by NS4B and HCV via EOR were found to promote human hepatocyte viability. Taken together, these findings revealed that HCV NS4B might contribute to HCC by activating the EOR-mediated cancer-related STAT3 pathway, and this could provide novel insights into HCV-induced HCC.

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Title: Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response
Authors: Lingbao Kong
Shanshan Li
Xilan Yu
Xiaonan Fang
Ahui Xu
Mingjie Huang
Xiaoyu Wu
Yunli Guo
Fenglin Guo
Jin Xu
Publication date: 01-08-2016
Publisher: Springer Vienna
Published in: Archives of Virology / Issue 8/2016
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-016-2892-x

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