2014 Fiscal Year Final Research Report
Functional analysis of MICA in hepatitis C virus-induced hepatocellular carcinoma and its therapeutic application
Project/Area Number |
24390184
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | The University of Tokyo |
Principal Investigator |
KATO NAOYA 東京大学, 医科学研究所, 准教授 (90313220)
|
Co-Investigator(Renkei-kenkyūsha) |
室山 良介
後藤 覚
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Project Period (FY) |
2012-04-01 – 2015-03-31
|
Keywords | 肝癌 / C型肝炎ウイルス / MICA / ゲノムワイド関連解析 / SNP / 薬剤スクリーニング / SAHA |
Outline of Final Research Achievements |
We identified the association between hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) and MICA single nucleotide polymorphism (SNP) by a genome wide association study (GWAS). Thus, we have aimed to analyze the function of MICA in HCV-induced HCC and to establish the way to prevent hepatocarcinogenesis through regulating MICA expression. First, the MICA SNP to regulate individual differences in MICA expression was examined, and two responsible SNPs were identified in the promoter region of MICA. Next, the drug to upregulate MICA was screened using HCC cells stably transfected by the reporter having MICA promoter region in its upstream and U.S. Food and Drug Administration (FDA)-approved drug library. SAHA most strongly upregulated MICA. Moreover, SAHA augmented NK cell cytotoxicity against HCC cells through upregulating MICA. Thus, SAHA could be the attractive option to treat HCV-induced HCC.
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Free Research Field |
消化器病学・肝臓病学
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