2017 Fiscal Year Final Research Report
Suppression of host cellular microRNA functions by hepatitis C virus infection and its possible implication in hepatocarcinogenesis
| Project/Area Number |
15K09035
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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 |
Gastroenterology
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| Research Institution | Jikei University School of Medicine (2016-2017)
National Institute of Infectious Diseases (2015) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | HCV / microRNA / miR-122 / miRISC / 肝発癌 |
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| 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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| Free Research Field |
消化器内科学、肝臓病学、ウイルス学
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