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癌抑制マイクロRNAを基点とした尿路上皮癌の新規分子ネットワークの解明

Research Project

Project/Area Number 23791764
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Urology
Research InstitutionKagoshima University

Principal Investigator

千代丸 剛  鹿児島大学, 医学部・歯学部附属病院, 医員 (60593796)

Project Period (FY) 2011
Project Status Discontinued (Fiscal Year 2011)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsマイクロRNA / 尿路上皮癌 / 癌抑制遺伝子
Research Abstract

【目的】尿路上皮癌におけるmicroRNA (miRNA)の発現解析に基づき、尿路上皮癌の癌抑制機能を有するmiRNAを基点とした、miRNA-mRNAの分子ネットワークを網羅的に解析し、今後の新規治療法の開発の礎となるデータを拾得する研究である。【対象と方法】尿路上皮癌に共通して癌抑制遺伝子として機能するmiRNAsを尿路上皮癌由来細胞株(KK47、T24)に導入し、その後RNAを抽出し、miRNAの制御を受けて発現変動するタンパクコード遺伝子をマイクロアレイによる遺伝子発現解析で探索することである。【結果】splicing factor arginine/serine-rich 9 (SRSF9/SRp30c)はmiR-1の標的遺伝子、Transgelin2 (TAGLN2)、prothymosin-alpha (PTMA)、およびpurine nucleoside phosphorylase (PNP)はmiR-1およびmiR-133aに共通する標的遺伝子であることが分かった。これら標的遺伝子の臨床検体におけるmessengerRNAの発現は、正常尿路上皮と比べて尿路上皮癌で有意に上昇していた。また機能解析実験においてはこれらの標的遺伝子のノックダウンにより尿路上皮癌細胞の増殖能・浸潤能・遊走能が有意に低下することが明らかとなった。SRSF9/SRp30cはcaspase-3/7によるアポトーシス経路を抑制することが明らかになった。またmiR-218とmiR-574-3pは同様に癌抑制的miRNAであるが、尿路上皮癌におけるChromosomal Genomic Hybridization (CGH)で明らかになった4番染色体の遺伝子欠失領域にコードされ、新たなmiRNAの発現調節機序と考えられた。【結論】尿路上皮癌における複数の新たな癌抑制機序が明らかになった。

Report

(1 results)
  • 2011 Annual Research Report
  • Research Products

    (8 results)

All 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Novel oncogenic function of mesoderm development candidate 1 and its regulation by MiR-574-3p in bladder cancer cell lines.2012

    • Author(s)
      Tatarano S, Chiyomaru T, Kawakami K, Enokida H, Yoshino H, Hidaka H, Nohata N, Yamasaki T, Gotanda T, Tachiwada T, Seki N, Nakagawa M.
    • Journal Title

      International Journal of Oncology

      Volume: 40 Issue: 4 Pages: 951-959

    • DOI

      10.3892/ijo.2011.1294

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor suppressive microRNA-1 mediated novel apoptosis pathways through direct inhibition of splicing factor serine/arginine-rich 9 (SRSE9/SRp30c) in bladder cancer2012

    • Author(s)
      Yoshino, at al
    • Journal Title

      Biochemical and Biophysical Research Communication

      Volume: 417 Pages: 588-593

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel molecular targets regulated by tumor suppressors microRNA-1 and microRNA-133a in bladder cancer2012

    • Author(s)
      Yamasaki, at al
    • Journal Title

      International Journal of Oncology

      Volume: 40 Pages: 1821-1830

    • DOI

      10.3892/ijo.2012.1391

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer2011

    • Author(s)
      Tatarano, et al
    • Journal Title

      International Journal of Oncology

      Volume: 39 Pages: 13-21

    • DOI

      10.3892/ijo.2011.1012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] The tumor suppressive miRNA cluster of miR-1 and miR-133a targets oncogenic TAGLN2 gene in bladder cancer2011

    • Author(s)
      Yoshino, et al
    • Organizer
      2011 American Urological Association
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-05-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional role of LASP1 in bladder cancer cell viability and its regulation by microRNAs2011

    • Author(s)
      Chiyomaru, et al
    • Organizer
      2011 American Urological Association
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-05-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] MiR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer2011

    • Author(s)
      Tatarano, et al
    • Organizer
      2011 American Urological Association
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-05-15
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://genomejet.jp/

    • Related Report
      2011 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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