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Prediction of drug sensitivity and development of a therapeutic strategy by microRNAs in lung cancer

Research Project

Project/Area Number 21591008
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNippon Medical School

Principal Investigator

SEIKE Masahiro  日本医科大学, 医学部, 准教授 (30366687)

Co-Investigator(Kenkyū-buntansha) GEMMA Akihiko  日本医科大学, 大学院・医学研究科, 教授 (20234651)
峯岸 裕司  日本医科大学, 医学部, 講師 (80386234)
Co-Investigator(Renkei-kenkyūsha) MINEGISHI Yuji  日本医科大学, 医学部, 講師 (80386234)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsマイクロRNA / 肺癌 / 薬剤感受性
Research Abstract

We tried to identify microRNAs(miRNAs) associated with drug sensitivity of lung cancer and establish a new therapeutic strategy in lung cancer. First, we analyzed miRNA expression profiles of 30 lung cancer cell lines using Taqman MicroRNA Arrays. Four miRNAs(miR-21, miR-31, miR-193b and miR-365) were common miRNAs correlated with the sensitivity of lung cancer to nine anticancer drugs. Next, we analyzed the antitumor effects of enzastaurin in 22 lung cancer cell lines. To identify miRNA associated with this sensitivity, we conducted a miRNA expression profiling study on the same set of cell lines. We found that miR-21 affects the response to enzastaurin through the JAK/STAT signaling pathway in lung cancer. Finally, we analyzed miR-23a/24/27a expression in 10 non-small cell cancer cell lines by real-time PCR analysis. Correlation between expression of these miRNAs and epithelial-mesenchymal transition(EMT) was evaluated. We found that miR-23a regulated TGF-β-induced EMT by targeting E-cadherin and contributed to EGFR-TKI resistance of lung cancer cells. These miRNAs associated with drug sensitivity may be useful as new therapeutic targets in lung cancer.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (17 results)

All 2012 2011 2010 2009

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (12 results) Book (1 results)

  • [Journal Article] MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells2012

    • Author(s)
      Mengru C, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Gemma A
    • Journal Title

      Int J Oncol

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules2012

    • Author(s)
      Shimokawa T, Seike M, Soeno C, Uesaka H, Miyanaga A, Mizutani H, Kitamura K, Minegishi Y, Noro R, Okano T, Yoshimura A, Gemma A
    • Journal Title

      Br J Cancer

      Volume: 106(5) Issue: 5 Pages: 867-75

    • DOI

      10.1038/bjc.2012.7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enzastaurin has anti-tumour effects in lung cancers with overex pressed JAK pathway molecules2012

    • Author(s)
      Shimokawa T
    • Journal Title

      Br J Cancer

      Volume: 106巻 Pages: 867-875

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner2010

    • Author(s)
      Mizutani H, Okano T, Minegishi Y, Matsuda K, Sudoh J, Kitamura K, Noro R, Soeno C, Yoshimura A, Seike M, Gemma A
    • Journal Title

      Oncology Letter

      Volume: 1 Issue: 6 Pages: 1011-1016

    • DOI

      10.3892/ol.2010.190

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] miR-23aはSmad依存的にTGFβ誘導上皮間葉移行(EMT)を制御する2011

    • Author(s)
      清家正博、野呂林太郎、峯岸裕司、添野千絵、吉村明修、弦間昭彦
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2011 Final Research Report
  • [Presentation] miR-23aはSmad依存的にTGFβ誘導上皮間葉移行(EMT)を制御する2011

    • Author(s)
      清家正博
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肺癌の個別化治療とトランスレーショナルリサーチの現状2011

    • Author(s)
      清家正博
    • Organizer
      日本医科大学オーダーメイド医療講演会
    • Place of Presentation
      東京
    • Year and Date
      2011-09-12
    • Related Report
      2011 Final Research Report
  • [Presentation] 肺癌の発生と薬剤感受性に関与するmiR-21の意義2011

    • Author(s)
      清家正博
    • Organizer
      第20回日本癌病態治療研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-17
    • Related Report
      2011 Final Research Report
  • [Presentation] 肺がん細胞の薬剤感受性に関与するマイクロRNA発現プロファイル2010

    • Author(s)
      清家正博、岡野哲也、添野千絵、峯岸裕司、野呂林太郎、吉村明修、弦間昭彦
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-10-24
    • Related Report
      2011 Final Research Report
  • [Presentation] 肺癌のEGFR-TKI感受性に関するmicroRNA研究2010

    • Author(s)
      清家正博
    • Organizer
      第5回肺癌分子病態研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-09-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Gene expression profiles in lung cancer cells cooperated with drug sensitivity to PKC inhibitor enzastaurin2010

    • Author(s)
      清家正博, 他
    • Organizer
      AACR 101st Annual Meeting 2010
    • Place of Presentation
      米国ワシントンDC
    • Year and Date
      2010-04-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Gene expression profiles in lung cancer cells cooperated with drug sensitivity to PKC inhibitor enzastaurin2010

    • Author(s)
      Seike M, Smimokawa T, Soeno C, Okano T, Minegishi Y, Yoshimura A and Gemma A
    • Organizer
      101st AACR Annual Meeting
    • Place of Presentation
      Washington DC
    • Year and Date
      2010-04-06
    • Related Report
      2011 Final Research Report
  • [Presentation] 非喫煙者肺癌およびEGFR-TKI感受性に関与するmiR-21の役割2009

    • Author(s)
      清家正博、岡野哲也、吉村明修、弦間昭彦
    • Organizer
      第50回日本肺癌学会総会
    • Year and Date
      2009-11-13
    • Related Report
      2011 Final Research Report
  • [Presentation] 肺癌の診断および治療戦略におけるmiRNA研究2009

    • Author(s)
      清家正博
    • Organizer
      私立大学戦略的研究基盤形成支援事業シンポジウ
    • Place of Presentation
      東京
    • Year and Date
      2009-11-07
    • Related Report
      2011 Final Research Report
  • [Presentation] 非喫煙者肺癌およびEGFR-TKI感受性に関与するmiR-21の役割2009

    • Author(s)
      清家正博、岡野哲也、吉村明修、弦間昭彦
    • Organizer
      第68回日本癌学会総会
    • Year and Date
      2009-10-02
    • Related Report
      2011 Final Research Report
  • [Presentation] MicroRNA expression profiles modulate the drug sensitivity of lung cancer cells2009

    • Author(s)
      Seike M, Noro R, Soeno C, Shimokawa T, Miyanaga A, Yoshimura A and Gemma A
    • Organizer
      100th AACR Annual Meeting
    • Place of Presentation
      Denver
    • Year and Date
      2009-04-19
    • Related Report
      2011 Final Research Report
  • [Book] 抗癌剤の効果予測因子としてのバイオマーカー2010

    • Author(s)
      清家正博、弦間昭彦
    • Publisher
      科学評論社
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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