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A novel regulatory mechanism of TGF-beta pathway via long non-coding RNA

Research Project

Project/Area Number 16H04696
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Kitagawa Masatoshi  浜松医科大学, 医学部, 教授 (50294971)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
KeywordsTGF-beta / 長鎖ncRNA / がん細胞 / 上皮間葉転換 / TGF-β / シグナル伝達 / がん / ノンコーディングRNA / Smad / lncRNA / がん制御遺伝子
Outline of Final Research Achievements

We identified a novel lncRNA ELIT-1 (EMT-associated lncRNA induced by TGFbeta-1) involved in TGFbeta-signaling. ELIT-1 is transcriptionally and rapidly induced via TGFbeta-Smad-pathway and promotes EMT and cell migration via expression of EMT-associated genes such as Snail and N-cadherin. A positive correlation between high expression of ELIT-1 and poor prognosis in lung adenocarcinoma cancer patients. ELIT-1 bound to Smad3 but not Smad2 and facilitated recruitment of Smad3 to promoter regions of the target genes. These results suggest that ELIT-1 binds to Smad3 and recruits to the Smad3-target genes such as Snail as a novel mediator of TGFbeta-Smad pathway and thereby it is involved in promotion of EMT.

Academic Significance and Societal Importance of the Research Achievements

我々が見出した新規lncRNA ELIT-1は、Smad3と結合することによりvimentin、Snail等の上皮間葉転換(EMT)関連遺伝子の発現制御に関与して、EMTの誘導を正に制御して浸潤能の増強に関与する。さらにELIT-1の高発現は肺腺がんの予後不良と相関することも判明した。よってELIT-1はがんの予後マーカーとなる可能性がある。さらにELIT-1の発現や機能の阻害する化合物はがん転移抑制薬となる可能性がある。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (13 results)

All 2019 2017 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Journal Article] Long Noncoding RNA ELIT-1 Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial-Mesenchymal Transition.2019

    • Author(s)
      Sakai S, Ohhata T, Kitagawa K, Uchida C, Aoshima T, Niida H, Suzuki T, Inoue Y, Miyazawa K, Kitagawa M.
    • Journal Title

      Cancer Res

      Volume: 79(11) Issue: 11 Pages: 2821-38

    • DOI

      10.1158/0008-5472.can-18-3210

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 新規 lncRNA ELIT-1 は Smad3 コファクターとして TGF βシグナリング と EMT を促進する2019

    • Author(s)
      北川雅敏,酒井聡,大畑樹也
    • Organizer
      第71回日本細胞生物学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Smad3の標的遺伝子へのリクルーターとして機能する新規lncRNA ELIT-12019

    • Author(s)
      北川雅敏,酒井聡,大畑樹也
    • Organizer
      第21回日本RNA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TGF βによって誘導され、TGF β-Smadシグナリングの正の制御因子として機能する新規lncRNA ELIT-12019

    • Author(s)
      北川雅敏,酒井聡,大畑樹也
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A novel lncRNA ELIT-1 promotes Snail induction and EMT via TGFb signaling2019

    • Author(s)
      M.Kitagawa, S.Sakai
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 5.Long noncoding RNA ELIT-1 act as a Smad3 cofactor to promotes TGF-beta-Smad signaling and epithelial-mesenchymal transition2019

    • Author(s)
      M.Kitagawa,T.Ohhata, S.Sakai
    • Organizer
      EMBO Workshop The Non-Coding Genome
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 上皮間葉転換に関与する新規 lncRNA2017

    • Author(s)
      北川 雅敏,大畑 樹也,酒井 聡
    • Organizer
      第69回日本細胞生物学会大会 シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] A novel lncRNA ELIT-1 promotes epithelial-mesenchymal transition via TGFbeta-Smad pathway2017

    • Author(s)
      Masatoshi Kitagawa, Tatsuya Ohhata, Satoshi Sakai
    • Organizer
      第43回内藤コンファレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト肺腺癌において肺転写因子であるNKX2-1はサイクリンD1の転写亢進に関与する2017

    • Author(s)
      Masatoshi Kitagawa, Satoshi Sakai, Masanori Harada
    • Organizer
      第76回日本癌学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TGFbeta-Smad経路を介した上皮間葉転換を制御する新規長鎖ncRNA2017

    • Author(s)
      酒井聡、大畑樹也、北川雅敏
    • Organizer
      2017年度生命科学系学会合同年次大会 (ConBio2017) ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Remarks] 医学科講座等紹介 分子生物学講座

    • URL

      https://www.hama-med.ac.jp/education/fac-med/dept/mol-biol/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 浜津医科大学 分子生物学講座

    • URL

      https://www.hama-med.ac.jp/education/fac-med/dept/mol-biol/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 浜松医科大学分子生物学講座

    • URL

      http://www.hama-med.ac.jp/education/fac-med/dept/mol-biol/index.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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