| Project/Area Number |
17K17274
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgical dentistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Research Collaborator |
Nakayama Hideki
Hirosue Akiyuki
Yamamoto Tatsurou
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ANGPTL4 / エピジェネティクス / HIF-1α / 口腔癌 / 細胞外環境応答 / HIF1α / CTCF |
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| Outline of Final Research Achievements |
High expression of ANGPTL4 is known as a poor prognostic factor in various carcinomas.Also in oral cancer, its high expression has been reported to have a correlation with poor prognosis, but the mechanism of regulation of ANGPTL4 expression in a hypoxic environment is unclear.I performed the experiment using an oral cancer cell line cultured in a hypoxic environment to confirm the increase in the expression of ANGPTL4.I confirmed the HIF-1α binding site at the ANGPTL4 gene locus.At the same site, increased binding ofH3K27Ac (acetylation of histone H3 lysine 27), a mark of transcriptional activation, was confirmed.It is suggested HIF-1α is involved in the gene expression regulation of ANGPTL4 via an epigenetic mechanism.
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| Academic Significance and Societal Importance of the Research Achievements |
同じ転写のアウトプットでも、そのアウトプットにまで至る過程は一つではなく、転写因子の結合や高次クロマチン構造の状態によって様々である。ANGPTL4は脂質代謝やインスリン抵抗性といった生物の恒常性維持の観点からも重要な因子であるため、治療標的として考えた際に単純にANGPTL4の発現を低下させてやれば良いわけではない。悪性基質を獲得した癌細胞特異的に起こっているANGPTL4遺伝子のエピゲノムを介した転写制御のメカニズムを解明することで、より特異性のある治療標的としての因子を抽出することができる可能性がある。
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