2013 Fiscal Year Final Research Report
Study on the mechanisms of HCV-mediated carcinogenesis
| Project/Area Number |
23590543
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kobe University |
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Principal Investigator |
DENG Lin 神戸大学, 医学(系)研究科(研究院), 助教 (40437497)
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| Co-Investigator(Kenkyū-buntansha) |
HOTTA Hak 神戸大学, 大学院医学研究科, 教授 (40116249)
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| Project Period (FY) |
2011 – 2013
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| Keywords | C型肝炎ウイルス / 発癌 / NS5A / SMYD3 / AGR3 |
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| Research Abstract |
Hepatitis C Virus (HCV) NS5A is a multifunctional protein involved in HCV life cycle and HCV-induced liver pathologies. To elucidate the role of NS5A in HCV pathogenesis, we searched for host proteins interacting with NS5A by tandem affinity purification and identified a novel NS5A-interacting protein, SET and MYND domain-containing 3 (SMYD3), a histone methyltransferase involved in the proliferation of cancer cells. The interaction of NS5A with SMYD3 was confirmed by co-immunoprecipitation, proximity ligation assay, and confocal microscopy. NS5A predominately colocalized with SMYD3 in the cytoplasm. Moreover, the interaction between NS5A and SMYD3 transcriptionally activated AGR3, which is involved in breast, prostate and ovary tumorigenesis and belongs to the family of protein disulfide isomerases. Taken together, these data suggest that the interaction between NS5A and SMYD3 causes hepatocytic dysfunction through upregulation of AGR3 expression.
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[Journal Article] Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus2014
Author(s)
Ratnoglik SL, Aoki C, Sudarmono P, Komoto M, Deng L, Shoji I, Fuchino H, Kawahara N, Hotta H
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Journal Title
Microbiol Immunol
Volume: 58(3)
Pages: 188-94
DOI
Peer Reviewed
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[Journal Article] Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species2014
Author(s)
Adianti M, Aoki C, Komoto M, Deng L, Shoji I, Wahyuni TS, Lusida MI, Soetjipto, Fuchino H, Kawahara N, Hotta H
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Journal Title
Microbiol Immunol
Volume: 58(3)
Pages: 180-7
DOI
Peer Reviewed
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[Journal Article] Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus2013
Author(s)
Wahyuni TS, Tumewu L, Permanasari AA, Apriani E, Adianti M, Rahman A, Widyawaruyanti A, Lusida MI, Fuad A, Soetjipto D, Nasronudin D, Fuchino H, Kawahara N, Shoji I, Deng L, Aoki C, Hotta H
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Journal Title
Virol J
Volume: 10(1)
Pages: 259
DOI
Peer Reviewed
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[Journal Article] Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load2012
Author(s)
Kim SR, El-Shamy A, Imoto S, Kim KI, Ide YH, Deng L, Shoji I, Tanaka Y, Hasegawa Y, Ota M, Hotta H
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Journal Title
J Gastroenterol
Volume: 47(10)
Pages: 1143-51
DOI
Peer Reviewed
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[Journal Article] Sequence heterogeneity in NS5A of hepatitis C virus genotypes 2a and 2b and clinical outcome of pegylated-interferon/ribavirin therapy2012
Author(s)
El-Shamy A, Shoji I, Kim SR, Ide Y, Imoto S, Deng L, Yoon S, Fujisawa T, Tani S, Yano Y, Seo Y, Azuma T, Hotta H
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Journal Title
PLoS One
Volume: 7(2)
Pages: e30513
DOI
Peer Reviewed
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