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Function analysis of microRNAs regulated by HDAC inhibitors in multiple myelomas

Research Project

Project/Area Number 17K16179
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionAkita University

Principal Investigator

Ikeda Sho  秋田大学, 医学部附属病院, 医員 (20791495)

Research Collaborator Tagawa Hiroyuki  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords多発性骨髄腫 / microRNA / HDAC阻害薬
Outline of Final Research Achievements

We studied to elucidate target genes of the HDAC inhibitor panobinostat, a novel therapeutic agent for multiple myeloma, and to stratify susceptible patients. By focusing on microRNA-188 whose expression is commonly elevated by HDAC inhibitors by comprehensive microRNA expression analysis, it was found that its target is the IL-6 receptor.
It was thought that HDAC inhibitors may inhibit the survival of myeloma cells by restoring the expression of tumor suppressive microRNAs. In addition, if tumor survival is dependent on IL-6, the effects of HDAC inhibitors are likely to be high, and we plan to review patient specimens and clinical data in the future.

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫は悪性の血液腫瘍であり、次々と新規薬剤が登場し予後は延長しているものの、やがて新規薬剤へ抵抗性を獲得することや、新規薬剤に初めから耐性を示すクローンが存在することが認められる。HDAC阻害薬は近年骨髄腫に対し使用できるようになった、エピジェネティクスを標的とする新規薬剤であるが、その感受性は患者により大きく差異が認められる。HDAC阻害薬の標的microRNAや遺伝子を検討することで、HDAC阻害薬感受性患者の抽出ができる可能性がある。今回の研究でHDAC阻害薬はIL-6経路を阻害する可能性があり、今後さらに研究を進める予定である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] マイクロRNAを介した治療抵抗性の機序2018

    • Author(s)
      池田翔、田川博之
    • Journal Title

      血液内科

      Volume: 77(3) Pages: 336-342

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Hypoxia-inducible KDM3A addiction in multiple myeloma.2018

    • Author(s)
      Ikeda S, Kitadate A, Abe F, Takahashi N, Tagawa H.
    • Journal Title

      Blood Advances

      Volume: 2(4) Issue: 4 Pages: 323-334

    • DOI

      10.1182/bloodadvances.2017008847

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 骨髄腫を育む骨髄微小環境 Hypoxia, 血管新生 VEGF ほか.2018

    • Author(s)
      池田翔、田川博之
    • Journal Title

      多発性骨髄腫 Updating 10::骨髄腫治療を理解するための Myeloma Biology(10)

      Volume: 10 Pages: 176-182

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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