2020 Fiscal Year Final Research Report
Significance of histone methylation in liver carcinogenesis and its possibility as therapeutic target
| Project/Area Number |
18K15741
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | エピゲノム異常 / 肝癌 / ヒストン修飾 / DNA損傷 / アポトーシス / G9a |
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| Outline of Final Research Achievements |
Histone methyltransferase G9a is involved in various biological functions and diseases. Using liver-specific G9a-deficient mice, we found that hepatocarcinogenesis is suppressed in G9a-knockout livers. As a result of comprehensive gene expression analysis and chromatin immunoprecipitation using mouse liver, we found that G9a contributes to the induction of apoptosis in DNA-damaged hepatocytes through the regulation of p53 target gene expression. Inhibition of G9a attenuates liver carcinogenesis from DNA-damaged hepatocytes and is expected to be a therapeutic target.
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| Free Research Field |
消化器内科 肝臓病学
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| Academic Significance and Societal Importance of the Research Achievements |
肝癌は難治癌のひとつであり、特に進行肝癌に対しては未だ有効な治療薬が少なく新規治療法の開発が望まれている。慢性肝炎により誘導されるエピゲノム異常が肝発癌に重要な役割を担うことが知られてきているが、本研究の成果により、エピゲノム修飾因子のひとつであるヒストンメチル化酵素G9aがDNA損傷からの肝発癌に重要な役割を担うことが明らかとなった。G9a阻害剤により肝癌発生を抑制できる可能性があり、肝癌に対する新規創薬のターゲットとなることが期待される。
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