• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

肺癌におけるマイクロRNA発現の異常と転写制御崩壊の基礎・臨床的検討

Research Project

Project/Area Number 20659129
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

高井 大哉  The University of Tokyo, 医学部附属病院, 講師 (90361493)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2008: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsマイクロRNA / 原発性肺癌 / 転写制御
Research Abstract

申請者らは以前よりヒト癌におけるDNAメチル化による遺伝子発現抑制を研究してきたが,DNAメチル化によるマイクロRNAの発現低下が報告され始めるに至り,今回ヒト肺癌におけるマイクロRNAのDNAメチル化による発現低下を網羅的に検討した.まず英国サンガー研究所のマイクロRNAデータベースより678個のヒトの全マイクロRNAの情報を得て,染色体上にマッピングし,DNAメチル化による転写制御の中心となるCpGアイランド上にある,CpGアイランドの下流1000塩基以内にある,CpGアイランドをプロモータにもつ遺伝子のイントロンにあるものとして,常染色体上にある55のマイクロRNAについて,定量的RT-PCRを用いて検討を行った.対象とした細胞は腺癌細胞株4つ(EGFR突然変異あり2種,なし2種)と扁平上皮癌細胞株2つで,DNAの脱メチル化剤5-aza-d C処理前後で発現の増多のある14個のマイクロRNAについてヒト原発性肺癌15例(腺癌EGFR変異あり5例,無し5例,扁平上皮癌5例)で検討を行い6つのマイクロRNAが肺癌でDNAメチル化により発現低下が起きていることが示唆された.とりわけMir-43bはDNAメチル化による制御を受けており,標的遺伝子METは肺癌におけるイレッサ耐性に関係する遺伝子として,注目を集めている.またこのほかにいくつかのマイクロRNAがDNAメチル化によって制御されていることを明らかにし,現在投稿に向けた準備を進めている.

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (13 results)

All 2010 2009 2008 Other

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (6 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Identification of G0S2 as a gene frequently methylated in squamous lung cancer by combination of in silico and experimental approaches.2010

    • Author(s)
      Kusakabe M, et al.
    • Journal Title

      International Journal of Cancer. 126

      Pages: 1895-1902

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血清中のDNAのメチル化を用いた肺癌化学療法感受性予測2010

    • Author(s)
      高井大哉
    • Journal Title

      癌と化学療法 37

      Pages: 189-193

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Impact of DNA demethylation of the G0S2 gene on the transcription of G0S2 in squamous lung cancer cell lines with or without nuclear receptor agonists.2009

    • Author(s)
      Kusakabe M, et al.
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 1283-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肺癌のエピジェネティクス研究の進歩2009

    • Author(s)
      高井大哉
    • Journal Title

      日本臨床 67

      Pages: 2387-96

    • Related Report
      2009 Annual Research Report
  • [Presentation] 肺癌とエピジェネティクス2009

    • Author(s)
      高井大哉
    • Organizer
      日本呼吸器学会第49回総会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2009-06-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] Genome structure-based screening for MicroRNAs epigenetically silenced by DNA methylation in non-small cell lung cancer2009

    • Author(s)
      Watanabe K, et al.
    • Organizer
      American Association for Cancer Research, Annual Meeting
    • Place of Presentation
      Denver, CO, USA
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Novel approach to identify methylated genes in non-small cell lung cancer and analyses of methylation Profile2008

    • Author(s)
      Kusakabe M, Takai D et al.
    • Organizer
      67th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] Knockdown of Tgfβ1 with Replication-Defective Serotype 2/5 Adeno-Associated Virus Carrying Short Hairpin RNA2008

    • Author(s)
      Kage H, Takai D et al.
    • Organizer
      48th Annual Meeting of the Japanese Respiratory Society
    • Place of Presentation
      Kobe,Japan
    • Year and Date
      2008-06-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] Functional Analysis of PIWIL4 in the induction of H3K9 Methylation at the p16Ink4a Locus2008

    • Author(s)
      Aki N, Takai D et al.
    • Organizer
      American Association for Cancer Research Special Conference on Cancer Research Cancer Epigenetics
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2008-05-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] Novel Approach to Identify Aberrantly Methylated Genes in Non-small Cell Lung Cancer and Methylation of GOS2 as Possible Biomarker of Squamous Lung Cancer2008

    • Author(s)
      Kusakabe M, Takai D et al.
    • Organizer
      American Association for Cancer Research Special Conference on Cancer Research Cancer Epigenetics
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2008-05-29
    • Related Report
      2008 Annual Research Report
  • [Book] 実験医学別冊注目のバイオ実験シリーズ-エピジェネティクス実験プロトコール-(分担)2008

    • Author(s)
      牛島俊和,眞貝洋一編
    • Total Pages
      267
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://kokyuki.umin.jp/305.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://kokyuki.umin.jp/305.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi