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Use of genome-wide RNAi screening to identify modes of action of bioactive compounds

Research Project

Project/Area Number 15K12759
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Matsumoto Ken  国立研究開発法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (60222311)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords化合物 / RNAi / スクリーニング / 標的同定 / shRNAスクリーニング / 化合物標的
Outline of Final Research Achievements

Genome-wide RNA interference (RNAi) with pooled and barcoded short-hairpin RNA (shRNA) libraries provides a powerful tool for identifying cellular components that are relevant to the modes/mechanisms of action of bioactive compounds. We used multiplex barcode sequencing technology which enables parallel analysis of multiple samples. An shRNA library screen with this system revealed that downregulation of ATP1A1, a catalytic subunit of Na+/K+ ATPase, conferred significant sensitivity to aurilide B, a natural marine product that induces mitochondria-mediated apoptosis. Combined treatment with ouabain which inhibits Na+/K+ ATPase by targeting catalytic subunits potentiated sensitivity to aurilide B.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] A quantitative shRNA screen identifies ATP1A1 as a gene that regulates cytotoxicity by aurilide B.2017

    • Author(s)
      Takase, S., Kurokawa, R., Arai, D., Kanto, K. K., Okino, T., Nakao, Y., Kushiro, T., Yoshida, M., and Matsumoto, K.
    • Journal Title

      Scientific Reports

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro2017

    • Author(s)
      Lim, J. P., Shyamasundar, S., Gunaratne, J., Scully, O. J., Matsumoto, K., and Bay, B.-H.
    • Journal Title

      BMC Cancer

      Volume: 17 Issue: 1 Pages: 201-201

    • DOI

      10.1186/s12885-017-3187-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PRAS40 deregulates apoptosis in Ewing sarcoma family tumors by enhancing the insulin receptor/Akt and mTOR signaling pathways.2016

    • Author(s)
      Lv, D., Liu, J., Guo, L., Wu, D., Matsumoto, K., and Huang, L.
    • Journal Title

      American Journal of Cancer Research

      Volume: 6 Pages: 486-497

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the determinants of 2-deoxyglucose sensitivity in cancer cells by shRNA library screening2015

    • Author(s)
      Kobayashi, H. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 467 Issue: 1 Pages: 121-127

    • DOI

      10.1016/j.bbrc.2015.09.106

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 網羅的shRNAスクリーニングによる海洋天然物aurilide Bの作用に関わる遺伝子の同定2017

    • Author(s)
      高瀬翔平、黒川留美、新井大祐、中尾洋一、久城哲夫、吉田 稔、松本 健
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] shRNAスクリーニング法の改良による化合物の標的経路の同定の効率化2017

    • Author(s)
      高瀬翔平、黒川留美、新井大祐、中尾洋一、久城哲夫、松本 健、吉田 稔
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大学(京都府・京都市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Remarks] 研究者ホームページ

    • URL

      http://www.riken.jp/matsumok/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www.riken.jp/matsumok/index.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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