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Investigation of miRNA targeting Notch1

Research Project

Project/Area Number 26830115
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionTokai University

Principal Investigator

OKUYAMA Kazuki  東海大学, 医学部, 客員准教授 (60712750)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsT-ALL / Notch1 / miRNA / Notch / T細胞性リンパ芽球性白血病 / B細胞分化
Outline of Final Research Achievements

Notch1 mutation is one of the most frequent mutation found in T-ALL. miRNA is non-coding RNA regulating target genes post-transcriptionally. Recently miRNAs are suggested as potential biologics. In this study, I investigated miRNA targeting Notch1.
Focusing on the function of Notch receptors as adhesion molecules, I established a screening system for miRNA targeting Notch1. Library of murine miRNAs was transduced into T-ALL-derived MOLT-4, and MOLT-4 cells were incubated on OP9 expressing Notch ligand, Dll4. If transduced miRNA represses Notch1 in MOLT-4, it is suggested the adhesion of MOLT4 to Dll4 would be interfered. By use of this system, I obtained 5 candidate miRNAs. One of them, miR-669m-1 functionally suppressed Notch1 in vitro. Next I performed bone-marrow transfer experiments, and found that miR-669m-1 expressing LSK cells efficiently gave rise to B cells. Since Notch1 suppresses B-lymphopoiesis, miR-669m-1 was suggested to enhance B cell development by repressing Notch1.

Report

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

    (12 results)

All 2015 2014

All Journal Article (5 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 2 results)

  • [Journal Article] 白血病細胞の分化誘導と非コードRNA miR-1262015

    • Author(s)
      奥山一生、幸谷愛
    • Journal Title

      感染 免疫 炎症

      Volume: 45(2) Pages: 68-68

    • Related Report
      2015 Annual Research Report
  • [Journal Article] An evolutionary-conserved function of mammalian notch family members as cell adhesion molecules.2014

    • Author(s)
      Akihiko Murata, Miya Yoshino, Mari Hikosaka, Kazuki Okuyama, Lan Zhou, Seiji Sakano, Hideo Yagita, Shin-Ichi Hayashi
    • Journal Title

      PLoS One

      Volume: 9 Issue: 9 Pages: e108535-e108535

    • DOI

      10.1371/journal.pone.0108535

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel functional small RNAs are selectively loaded onto mammalian Ago12014

    • Author(s)
      Yamakawa, N. Okuyama, K. Ogata, J. Kanai, A. Helwak, A. Takamatsu, M. Imadome, K. I. Takakura, K. Chanda, B. Kurosaki, N. Yamamoto, H. Ando, K. Matsui, H. Inaba, T. Kotani, A.
    • Journal Title

      Nucleic Acids Res

      Volume: 未確定 Issue: 8 Pages: 5289-5301

    • DOI

      10.1093/nar/gku137

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Small RNA as a regulator of hematopoietic development, immune response in infection and tumorigenesis2014

    • Author(s)
      Okuyama K, Ogata J, Yamakawa N, Chanda B, Kotani A.
    • Journal Title

      International Journal of Hematology

      Volume: 99 Issue: 5 Pages: 553-60

    • DOI

      10.1007/s12185-014-1564-4

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] マイクロRNAによる血液細胞分化制御2014

    • Author(s)
      奥山一生, 幸谷愛
    • Journal Title

      血液内科

      Volume: 68 Pages: 725-729

    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of Notch-targeting miRNA that regulates B cell development and has therapeutic potential in T-ALL2015

    • Author(s)
      那須亮、奥山一生、扇屋大輔、穂積勝人、村田暁彦、安藤 潔、幸谷愛
    • Organizer
      第74回 日本癌学会学術総会
    • 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 Annual Research Report
  • [Presentation] Functional and comprehensive investigation of microRNA targeting Notch receptors2014

    • Author(s)
      K. Okuyama, K. Hozumi, A. Murata, K. Ando, A. Kotani
    • Organizer
      第42回日本免疫学会総会・学術集会
    • Place of Presentation
      京都 日本
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] The critical interaction between Epstein-Barr virus positive B-cells and tumor associated macrophages2014

    • Author(s)
      A. Sato, N. Yamakawa, K. Okuyama, A. Kotani, N. Nakamura, K. Ando
    • Organizer
      56th ASH Annual Meeting
    • Place of Presentation
      CA USA
    • Year and Date
      2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] EBF deficient hematopoietic progenitor cells potentially differentiated into immature B cell: EBF1 dispensable for B cell lineage commitment from pro-B to pre-B stage2014

    • Author(s)
      B. Chanda, T. Ikawa, K. Okuyama, K. Hozumi, K. Ando, A. Tojo, H. Kawamoto, A. Kotani
    • Organizer
      56th ASH Annual Meeting
    • Place of Presentation
      CA USA
    • Year and Date
      2014-12-06
    • Related Report
      2014 Research-status Report
  • [Presentation] MicroRNAライブラリーを用いたNotch受容体標的MicroRNAの探索2014

    • Author(s)
      奥山一生, 黒﨑なつみ, 水谷隆之, 大庭成喜, 恵口豊, 幸谷愛
    • Organizer
      第6回日本RNAi研究会
    • Place of Presentation
      広島 日本
    • Year and Date
      2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] 血液腫瘍におけるMicroRNA2014

    • Author(s)
      奥山一生, 幸谷愛
    • Organizer
      総合医学研究所・糖鎖科学研究所・創造科学技術研究機構 第6回公開合同シンポジウム
    • Place of Presentation
      神奈川 日本
    • Year and Date
      2014-07-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] MicroRNA-126による転写因子非依存的?なB細胞運命決定制御機構2014

    • Author(s)
      奥山一生
    • Organizer
      第10回麒麟塾
    • Place of Presentation
      東京 日本
    • Year and Date
      2014-07-12
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2017-05-10  

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