Suppression of host cellular microRNA functions by hepatitis C virus infection and its possible implication in hepatocarcinogenesis
Project/Area Number |
15K09035
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Jikei University School of Medicine (2016-2017) National Institute of Infectious Diseases (2015) |
Principal Investigator |
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | HCV / microRNA / miR-122 / miRISC / 肝発癌 / C型肝炎ウイルス / マイクロRNA |
Outline of Final Research Achievements |
The aims of this study were to test whether HCV affects the ability of microRNAs (miRNAs), including miR-122, to repress their endogenous targets, and if so, to address the underlying mechanism(s). The results showed that HCV infection led to increases in the expression of endogenous miRNA targets. This de-repression of miRNA targets was canceled in HCV subgenomic replicon (SGR) cells by supplementation of exogenous mature miRNAs. However, miRNA functions remained impaired in HCV-infected cells, suggesting the possible involvement of viral structural proteins in miRNA dysfunction. Interestingly, this miRNA dysfunction was reproduced in SGR cells by knocking down some of miRNA-induced silencing complex (miRISC) proteins, while overexpression of these proteins restored miRNA functions in HCV-infected cells. These results suggest that HCV structural proteins may induce the dysfunction of miRISC, resulting in the global de-repression of miRNA targets.
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid2018
Author(s)
Qin XY, Suzuki H, Honda M, Okada H, Kaneko S, Inoue I, Ebisui E, Hashimoto K, Carninci P, Kanki K, Tatsukawa H, Ishibashi N, Masaki T, Matsuura T, Kagechika H, Toriguchi K, Hatano E, Shirakami Y, Shiota G, Shimizu M, Moriwaki H, Kojima S
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Journal Title
Proc Natl Acad Sci U S A
Volume: 115
Issue: 19
Pages: 4969-4974
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Alpha-1 antichymotrypsin is involved in astrocyte injury in concert with arginine-vasopressin during the development of acute hepatic encephalopathy2017
Author(s)
Park J, Masaki T, Mezaki Y, Yokoyama H, Nakamura M, Maehashi H, Fujimi TJ, Gouraud SS, Nagatsuma K, Nakagomi M, Kimura N, Matsuura T
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Journal Title
PLoS One
Volume: 12
Issue: 12
Pages: e0189346-e0189346
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Interferon sensitivity-determining region of hepatitis C virus influences virus production and interferon signaling2017
Author(s)
Sugiyama R., Murayama A., Nitta S., Yamada N., Tasaka-Fujita M., Masaki T., Aly H. H., Shiina M., Ryo A., Ishii K., Wakita T. and Kato T.
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Journal Title
Oncotarget
Volume: 9
Issue: 5
Pages: 5627-5640
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of resistance-associated NS5A mutations in hepatitis C virus on viral production and susceptibility to antiviral reagents.2016
Author(s)
Nitta S, Asahina Y, Matsuda M, Yamada N, Sugiyama R, Masaki T, Suzuki R, Kato N, Watanabe M, Wakita T, Kato T.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 34652-34652
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Amino acid polymorphisms in hepatitis C virus core affect infectious virus production and major histocompatibility complex class I molecule expression2015
Author(s)
Tasaka-Fujita M, Sugiyama N, Kang W, Masaki T, Murayama A, Yamada N, Sugiyama R, Tsukuda S, Watashi K, Asahina Y, Sakamoto N, Wakita T, Shin EC, Kato T
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Journal Title
Sci Rep
Volume: 5
Issue: 1
Pages: 13994-14002
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Amino acid substitutions in IFN sensitivity-determining region of HCV-NS5A affect infectious virus production and ISG induction2016
Author(s)
Sugiyama R, Sugiyama N, Murayama A, Tasaka-Fujita M, Yamada N, Nitta S, Masaki T, Ishii K, Ryo A, Wakita T, Kato T
Organizer
23rd International Symposium on Hepatitis C Virus and Related Viruses
Place of Presentation
京都
Year and Date
2016-10-11
Related Report
Int'l Joint Research
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[Presentation] Induction of NTCP expression in a human HCC cell line by retinoic acid and its effect on host susceptibility to HBV infection2016
Author(s)
Masaki T, Matsumoto Y, Aizaki H, Nagamori S, Watashi K, Park J, Kanai Y, Kojima S, Wakita T, Matsuura T
Organizer
2016 International HBV Meeting
Place of Presentation
Seoul, Korea
Year and Date
2016-09-21
Related Report
Int'l Joint Research
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