| Project/Area Number |
17K16035
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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 |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
Teruyuki Sato 東北大学, 医学系研究科, 助教 (80736471)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 肺小細胞癌 / ポリコーム / エピゲノム / EZH2 |
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| Outline of Final Research Achievements |
Epigenetics modyfier genes are often harbors alterations in many cancers.Such genes affect cancer phenotype by modifying other gene expression. EZH 2 (Enhancer of Zeste 2), a component of the PRC2 complex, which is a histone H3K27me3 modifying enzyme, is up-regulated in small cell lung cancer. We treated NCI-H209 small cell lung cancer cell line with EZH2 inhibitor GSK126, and analysed H3K27me3 modification and gene expression changes with ChIP-seq and RNA-seq.We found expression of extracellular protein-related genes was restored by inhibition of EZH2, and it is thought that recognizability to the immune system may be enhanced.
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| Academic Significance and Societal Importance of the Research Achievements |
癌では多種の遺伝子に異常が起きているが、核内で遺伝子発現を調節するエピゲノム遺伝子の異常が癌の性質に及ぼす影響は不明である。ヒストンH3K27me3修飾酵素であるPRC2複合体の構成因子であるEZH 2（Enhancer of Zeste 2）は癌関連遺伝子として知られており、肺小細胞癌で発現上昇している。本研究では肺小細胞癌細胞株NCI-H209を用いてEZH2阻害剤GSK126処理を行い、ヒストンH3K27me3修飾および遺伝子発現変化を解析した。EZH2阻害によって細胞外蛋白関連遺伝子が発現回復しており、免疫機構への被認識性を高め、免疫療法の効果を増強する可能性が考えられた。
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