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Search for miRNAs that regulate stemness of breast cancer stem cell to find therapeutic targets of triple-negative breast cancer.

Research Project

Project/Area Number 26430109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionChiba University (2016)
The University of Tokyo (2014-2015)

Principal Investigator

Haraguchi Takeshi  千葉大学, 真菌医学研究センター, 特任助教 (10549455)

Co-Investigator(Kenkyū-buntansha) 伊庭 英夫  千葉大学, 真菌医学研究センター, 特任教授 (60111449)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsmicroRNA / microRNA inhibitor / 癌幹細胞 / EMT / 乳癌 / トリプルネガティブ
Outline of Final Research Achievements

Triple negative breast cancer cell line SUM149PT is composed of 2 subpopulations; epithelial-like EpCAM positive (EpCAM+) cells and mesenchymal-like EpCAM negative (EpCAM-) cells. In this study, we found that EpCAM+ cells had strong tumorigenicity and the expression levels of miR-200 family were high in only EpCAM+ cells.
When we suppressed the miR-200 family in EpCAM+ cells, conversion of EpCAM+ cells to EpCAM- cells occurred and the tumorigenicity of the EpCAM+ cells was reduced. Furthermore, we developed and used doxycycline-inducible miRNA inhibitory vector to construct EpCAM+ cell in which the activities of miR-200 family can be regulated by doxycycline. After tumor formation in xenograft mice transplanted with these cells, we inhibited miR-200 family and observed tumor regression. These results showed that miR-200 family was promising therapeutic targets of triple negative breast cancer.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) Remarks (2 results)

  • [Journal Article] The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells2017

    • Author(s)
      Hiroaki Hiramatsu, Kazuyuki Kobayashi, Kyousuke Kobayashi, Takeshi Hraguchi, Yasushi Ino, Tomoki Toda & Hideo Iba
    • Journal Title

      Sienctific Reports

      Volume: 7 Issue: 1 Pages: 889-889

    • DOI

      10.1038/s41598-017-00982-3

    • URL

      https://pure.teikyo.jp/en/publications/547dc474-7387-4760-bfa2-12548a02caa3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamics and plasticity of the epithelial to mesenchymal transition induced by miR-200 family inhibition2016

    • Author(s)
      Haraguchi, T, Kondo, M, Uchikawa, R, Kobayashi, K, Hiramatsu, H, Kobayashi, K , Chit, UW, Shimizu, T, Iba, H.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 1-12

    • DOI

      10.1038/srep21117

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines.2015

    • Author(s)
      Kobayashi, K., Sakurai, K., Hiramatsu, H., Inada, K., Shiogama, K., Nakamura, S.,  Suemasa, F., Kobayashi, K., Imoto, S., Haraguchi, T., Ito, H., Ishizaka, A., Tsutsumi, Y., & Iba H.
    • Journal Title

      Scientific Reports,

      Volume: 5:8428 Issue: 1 Pages: 8428-8428

    • DOI

      10.1038/srep08428

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] トリプルネガティブ乳癌の腫瘍形成能に関わるmicroRNAの同定2015

    • Author(s)
      内川 亮, 原口 健, 近藤 正幸, 小林 和善, 伊庭 英夫
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] グリオーマ幹細胞の幹細胞性の維持におけるSWI/SNFクロマチン構造変換複合体の役割2015

    • Author(s)
      平松 寛明、小林 和善、小林 郷介、原口 健、稲生 靖、藤堂 具紀、伊庭 英夫
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Brm型SWI/SNF複合体は転写因子SRFのMKL1依存的な活性を抑制することにより細胞の上皮性を維持している2015

    • Author(s)
      小林 和善, 平松 寛明, 小林 郷介, 原口 健, 伊庭 英夫
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 2 種の miRNA 阻害による乳癌幹細胞の造腫瘍能の抑制2015

    • Author(s)
      原口 健、近藤 正幸、伊庭 英夫
    • Organizer
      第74回日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] SWI/SNF クロマチン構造変換因子と miRNA の視点に立った上皮癌の遺伝子制御ネットワークの理解2015

    • Author(s)
      伊庭 英夫、小林 和善、平松 寛明、櫻井 浩平、稲田 健一、堤 寛、原口 健
    • Organizer
      第74回日本癌学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 新規TuD RNA発現レンチウイルスベクターを用いたmiR-200cの発現制御によるEMTの分子機構の解析2014

    • Author(s)
      近藤正幸、原口健、伊庭英夫
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Analysis on EMT using Tetracycline-inducible microRNA inhibitory vectors against miR-200c.2014

    • Author(s)
      原口健、近藤正幸、伊庭英夫
    • Organizer
      第73回日本癌学会学術
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Remarks] 千葉大学真菌医学研究センターRNA制御プロジェクト

    • URL

      http://www.pf.chiba-u.ac.jp/research/project/iba.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京大学医科学研究所宿主寄生体学分野

    • URL

      http://www.ims.u-tokyo.ac.jp/div-host-parasite/version1.html

    • Related Report
      2015 Research-status Report 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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