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miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the Inhibition of DCLK1

Research Project

Project/Area Number 16K10539
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyoto University

Principal Investigator

Hisamori Shigeo  京都大学, 医学研究科, 助教 (50534351)

Research Collaborator Sakaguchi Masazumi  京都大学大学院医学研究科, 消化管外科, 大学院生
Shimono Yohei  藤田医科大学医学部, 生化学講座, 教授
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大腸癌 / マイクロRNA / 大腸癌幹細胞 / 正常大腸幹細胞 / DCLK1 / 外科 / 癌
Outline of Final Research Achievements

DCLK1-positive colon cancer cells were widely distributed in the colon cancer specimens, while DCLK1-positive epithelial cells were rarely detected in normal colon tissues, including the crypt bottoms. MiRNA-137(miR-137) was highly expressed in the NCoSC population, whereas the DCLK1 mRNA expression was significantly upregulated in the CoCSC population. The defect in organoid development by the transduction of miR-137 and shRNAs were substantially rescued by co-expression of the exogenous DCLK1. Although miRNA-137 overexpression did not affect the organoid development of the normal intestine, miRNA-137 knockdown promoted the organoid development of normal colon cells. miR-137 has the potential function to suppress the tumorigenicity of CoCSCs and that maintained expression of miR-137 in NCoSCs contributes to suppress uncontrolled cell proliferation through the inhibition of DCLK1 expression.

Academic Significance and Societal Importance of the Research Achievements

正常大腸幹細胞(NCoSCs)と大腸癌幹細胞(CoCSCs)は、組織再形成・細胞増殖のため共通のメカニズムを有していると考えられている。近年マウスを用いた研究で、DCLK1が、正常大腸には発現せず、小腸腺腫の幹細胞にのみ発現していることが報告されたが、ヒトCoCSCsとDCLK1の発現については詳細な研究は進んでいなかった。
今回の我々の研究結果から、miR-137はDCLK1発現を制御することでCoCSCsの腫瘍形成能を抑制することが示唆された。本結果から正常大腸組織を障害せずCoCSCsを標的とした新規治療戦略を提示できる可能性があると考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the Inhibition of DCLK12018

    • Author(s)
      Sakaguchi M, Hisamori S, Oshima N, Sato F, Shimono Y, Sakai Y
    • Journal Title

      Mol Cancer Res

      Volume: 14 Pages: 354-362

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the inhibition of DCLK12017

    • Author(s)
      M Sakaguchi, S Hisamori, N Oshima, F Sato, Y Shimono, Y Sakai
    • Journal Title

      Molecular Cancerh Research

      Volume: 14 Pages: 354-362

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] miR-137/DCLK1 axis in colon cancer stem cells: An important regulator of tumorigenicity2018

    • Author(s)
      Sakaguchi M
    • Organizer
      第14回日本臨床腫瘍学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MicroRNA-137 regulates the tumorigenicity of colon cancer stem cells through the inhibition of DCLK12017

    • Author(s)
      久森重夫、坂口正純 他
    • Organizer
      第71回 日本消化器外科学会総会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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