Methylation dynamics in redox regulation - Elucidation of the molecular mechanisms of tumor metastasis
| Project/Area Number |
17K08277
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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 |
Biological pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原 宏和 岐阜薬科大学, 薬学部, 准教授 (30305495)
足立 哲夫 岐阜薬科大学, 薬学部, 教授 (40137063)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | SOD3 / がん / 活性酸素 / ヒストンメチル化 / FOXO1 / PRMT1 / H3K27トリメチル化 / JMJD3 / H4R3ジメチル化 / エピジェネティクス / 細胞遊走 / H3K27me3 / H4R3me2 / 酸化ストレス / がん転移 |
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| Outline of Final Research Achievements |
In this study, we investigated the role of histone methylation in extracellular redox regulation to elucidate the molecular mechanisms of tumor metastasis. We previously reported that DNA methylation within the promoter region of superoxide dismutase 3 (S0D3) play the critical role in its gene expression. Our present results clearly indicated that histone H4R3 dimehtylation is related to the expression of SOD3 in tumor cells and tumor-associated macrophages. Moreover, it was considered that transcription factor, FOXO1, and histone methyltransferase, PRMT1, play a key role in the regulation of SOD3.
Overall, our results suggested that FOXO1 and PRMT1 function as a key molecule for the regulation of SOD3 in tumor-related cells. Our findings could support to better understand the molecular mechanisms involved in tumor metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
がん増悪機構としての活性酸素の関与が指摘されているが、がん細胞転移あるいはがん細胞を取り巻く環境下における抗酸化酵素の発現制御機構は十分に解明されていない。本研究では、がん細胞およびその周りに存在するマクロファージにおける抗酸化酵素SOD3発現制御機構としてのヒストンメチル化の重要性ならびにその制御機構の一端を明らかにした。
以上より、本研究成果は活性酸素の産生増加あるいはその消去脳の低下による酸化ストレスの亢進を起点としたがん増悪・転移の分子機構の詳細解明に向けて、有益な情報を提供できたと考える。
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Report
(4 results)
Research Products
(16 results)
