title: The NS5A protein of hepatitis C virus transcriptionally upregulates the AGR3 gene expression.
abstract: The non-structural protein 5A (NS5A) of hepatitis C virus (HCV) is a multifunctional protein involved in the HCV lifecycle and pathogenesis. The precise molecular mechanisms of NS5A-mediated pathogenesis still remain to be clarified. In this study, we performed cDNA microarray analysis on NS5A-expressing HEK293 cells and the non-expressing control to screen the possible cellular genes dysregulated by NS5A. Subsequent quantitative real time PCR (qRT-PCR) analysis on NS5A-expressing cells and the control confirmed that NS5A upregulated the anterior gradient homolog 3 (AGR3) mRNA expression. The domain III of NS5A was responsible for the activation of AGR3 gene expression. AGR3 mRNA expression levels were upregulated also in Huh7.5 cells harboring a full-genome HCV-1b RNA replicon (FGR) and in those infected with HCV-2a. Moreover, AGR3 promoter activity was activated in NS5A-expressing cells, FGR-harboring cells and HCV-infected cells. Taken together, our present results suggest that HCV NS5A transcriptionally activates the cancer-associated AGR3 gene. This may be a novel mechanism of HCV-mediated pathogenesis, especially hepatocarcinogenesis.
authors: Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Ming
authors: M
authors: Chen
authors: Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.|Institute of Biochemistry and Molecular Biology, Hubei University, Wuhan, China.
authors: Xiang
authors: X
authors: Gan
authors: Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Lin
authors: L
authors: Deng
authors: Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Hak
authors: H
authors: Hotta
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D002352:Carrier Proteins; D009363:Neoplasm Proteins; D017361:Viral Nonstructural Proteins; C472588:AGR3 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: AGR3; NS5A; gene expression; hepatitis C virus; hepatocellular carcinoma; transcriptional activation