| Project/Area Number |
18K07942
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Shimane |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高山 哲治 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10284994)
佐藤 康史 徳島大学, 大学院医歯薬学研究部(医学域), 特任教授 (80343383)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 胃癌 / 薬剤感受性 / エピジェネティック調節 |
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| Outline of Final Research Achievements |
Jumonji domain-containing protein 2A (JMJD2A), histone lysine demethylases, has been implicated in tumorigenesis. However, its expression profile and role in drug resistance in gastric cancer (GC) remains unknown. Here, we investigated the role of JMJD2A in chemotherapeutic susceptibility and its clinical relevance in GC. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. Inhibition of CCDC8 restored drug resistance to docetaxel, cisplatin, and S-1. Our results indicate that JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in GC, and JMJD2A/CCDC8 is a potential therapeutic target.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、docetaxelおよびcisplatin、S-1対する耐性や感受性を規定する遺伝子として、JMJD2AおよびCCDC8が同定された。JMJD2AおよびCCDC8による新しい個別化医療に繋がる。また、これらを治療標的とした耐性克服薬の開発にも繋がる。さらに、他の癌種においても、JMJD2AおよびCCDC8 を含む候補遺伝子がバイオマーカーや耐性因子として機能している可能性があり、患者への負担の少ないオーダーメード医療への実現に繋がるだけでなく、耐性の克服を標的とした新薬の開発に繋がることが期待される。
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