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Mechanisms underlying gene expression mediated by 3'UTR of cancer-related gene

Research Project

Project/Area Number 19K22576
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Oneyama Chitose  愛知県がんセンター(研究所), 腫瘍制御学分野, 分野長 (90373208)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywordsがん関連遺伝子 / 3'UTR / 発現制御機構 / Rictor / 化合物 / 遺伝子発現 / 発現制御 / 低分子化合物
Outline of Research at the Start

本研究の目的は、がん関連遺伝子の3’UTRを介した新たな発現制御機構の解明である。
応募者はがん関連遺伝子の3'UTRを介した制御機構が、低分子化合物によって選択的に抑制できることを発見した。
本提案では、化合物の作用機序解明を通じ、特定の遺伝子発現をその転写後に制御する未知のメカニズムを明らかにすることを目指す。さらに、3'UTRを介した制御を標的とした低分子化合物探索の有用性を検証する。

Outline of Final Research Achievements

The aim of this study is to elucidate a new mechanism of expression regulation via the 3'UTR of cancer-related genes. Through our previous studies, we found a small molecule compound that suppresses the expression of Rictor gene, which is important for the survival and motility of cancer cells, via the 3'UTR. In order to identify candidate target proteins of the compounds, we identified three proteins known to be involved in the regulation of splicing, transcription, and translation by using the originally developed "target identification method using changes in protease sensitivity" in addition to the molecular probe method. We identified three proteins known to be involved in splicing, transcription, and translation regulation. Detailed analysis revealed that one RNA-binding protein was the target protein of the compound.

Academic Significance and Societal Importance of the Research Achievements

本研究内容にあるmiRNAの作用を低分子化合物により代替するというアイデアは極めて斬新なものである。元来miRNAは遺伝子の主に3'UTRを介し核酸配列の相補性に基づいて作用するため、核酸医薬を用いずに低分子を用いて代替できるとは考えられていなかった。しかし、私は3’UTRを標的とするスクリーニングに挑戦し、Rictor遺伝子の発現調節過程を低分子化合物によって制御することに成功した。本研究によってその分子基盤解明に挑戦することは、特定の遺伝子発現を3’UTRを介して制御する新しい原理の発見につながる点で、これまでの遺伝子発現制御機構の研究及び対がん創薬研究を大きく変革させる潜在性を有する。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (13 results) (of which Invited: 3 results) Remarks (1 results)

  • [Journal Article] Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells2021

    • Author(s)
      Tamako Nishimura*, Takuya Oyama*, Hooi Ting Hu*, Toshifumi Fujioka* et al.(*:equally contributed)
    • Journal Title

      Developmental Cell

      Volume: 56 Issue: 6 Pages: 842

    • DOI

      10.1016/j.devcel.2021.02.029

    • NAID

      120007172296

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] c-Src promotes tumor progression through downregulation of microRNA-129-1-3p2020

    • Author(s)
      Daisuke Okuzaki, Tomoe Yamauchi, Fumie Mitani, Mamiko Miyata, Risayo Watanabe, Chitose Oneyama
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 2 Pages: 418-428

    • DOI

      10.1111/cas.14269

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rictor promotes tumor progression of rapamycin-insensitive triple-negative breast cancer cells.2020

    • Author(s)
      Watanabe R, Miyata M, Oneyama C.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 531 Issue: 4 Pages: 636-642

    • DOI

      10.1016/j.bbrc.2020.08.012

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter2020

    • Author(s)
      Tomoya Hikita, Mamiko Miyata, Risayo Watanabe, Chitose Oneyama
    • Journal Title

      Scientific Reports

      Volume: 10(1) Issue: 1 Pages: 16616-16616

    • DOI

      10.1038/s41598-020-73580-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] チロシンキナーゼ:分子標的薬を極める2020

    • Author(s)
      小根山千歳
    • Journal Title

      産科と婦人科

      Volume: 10 Pages: 1150-1155

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Efficient Epstein-Barr Virus Progeny Production Mediated by Cancer-Derived LMP1 and Virally-Encoded microRNAs.2019

    • Author(s)
      Misako Yajima, Mamiko Miyata, Kazufumi Ikuta, Yasuhisa Hasegawa, Chitose Oneyama, Teru Kanda
    • Journal Title

      Microorganisms

      Volume: 7 Issue: 5 Pages: 119-119

    • DOI

      10.3390/microorganisms7050119

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] エクソソーム産生機構解明に向けた分泌制御因子の解析2021

    • Author(s)
      中山真穂、小野島大介、湯川博、小根山千歳、馬場嘉信
    • Organizer
      日本化学会第101春季大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 海洋薬用資源からのがんエクソソーム分泌阻害物質の探索2021

    • Author(s)
      林建宇、三谷文美絵、小根山千歳、荒井雅吉
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がんにおけるエクソソームの分泌亢進メカニズム2020

    • Author(s)
      小根山千歳
    • Organizer
      第72回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] がん細胞由来エクソソームのin vivoイメージング2020

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第72回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Src依存的エクソソーム分泌亢進におけるSNAREタンパク質の機能2020

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第72回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] In vivo imaging of long-term accumulated cancer-derived exosomes by CD63-fused BRET reporter2020

    • Author(s)
      Tomoya Hikita, Chitose Oneyama
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The role of SNARE-protein on the Src-mediated upregulation of exosome secretion2020

    • Author(s)
      Fumie Mitani, Chitose Oneyama
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞由来エクソソームのin vivoイメージング解析2020

    • Author(s)
      疋田智也、小根山千歳
    • Organizer
      第7回日本細胞外小胞学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Src依存的エクソソーム分泌亢進におけるSNAREタンパク質の役割2020

    • Author(s)
      三谷文美絵、小根山千歳
    • Organizer
      第7回日本細胞外小胞学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞のエクソソームの分泌亢進機構とその意義2020

    • Author(s)
      小根山千歳
    • Organizer
      第93回生化学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanisms governing exosome biogenesis in cancer cells2020

    • Author(s)
      小根山千歳
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] MicroRNA-mediated SFK signaling network in tumor progression2019

    • Author(s)
      小根山千歳、山内友恵、奥崎大介
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Srcがん化初期シグナルを制御するmicroRNAの役割2019

    • Author(s)
      山内友恵、小根山千歳、
    • Organizer
      第11回日本RNAi研究会
    • Related Report
      2019 Research-status Report
  • [Remarks] 愛知県がんセンター研究所 腫瘍制御学分野

    • URL

      https://www.pref.aichi.jp/cancer-center/ri/01bumon/06shuyo_uirusu/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2019-07-04   Modified: 2022-01-27  

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