title: Hepatitis C virus and its protein NS4B activate the cancer-related STAT3 pathway via the endoplasmic reticulum overload response.
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.
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China. lingbaok@hotmail.com.
authors.forename: Lingbao
authors.initials: L
authors.lastname: Kong
authors.affiliation: Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, College of Life Sciences, Hubei University, Wuhan, Hubei, China.|Department of Plant Pathology and Microbiology, Iowa State University, Ames, IA, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, College of Life Sciences, Hubei University, Wuhan, Hubei, China.
authors.forename: Xilan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Immunology and Pathogen Biology, Tongji University School of Medicine, 1239 Siping Rd, Shanghai, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Fang
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors.forename: Ahui
authors.initials: A
authors.lastname: Xu
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Huang
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wu
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Guo
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Guo
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C080107:NS4B protein, flavivirus; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D017361:Viral Nonstructural Proteins; D020780:Matrix Metalloproteinase 9