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Functional analysis of large intergenic non-coding RNAs regulated by p53 in cancers of digestive organs

Research Project

Project/Area Number 25460929
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

Masashi Idogawa  札幌医科大学, 医学部, 講師 (00404749)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsp53 / lncRNA / ChIP-seq / 癌 / lincRNA / non-coding RNA / 転写 / アポトーシス
Outline of Final Research Achievements

p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. To identify the direct transcriptional targets of p53, we performed chromatin immunoprecipitation together with next-generation sequencing (ChIP-seq) and searched for p53 binding motifs across the entire human genome. Among the identified ChIP-seq peaks, approximately half were located in an intergenic region. Therefore, we assumed large intergenic non-coding RNAs (lincRNAs) to be major targets of the p53 family. Through a combination of ChIP-seq and in silico analyses, we found 23 lincRNAs that are upregulated by the p53 family. Additionally, knockdown of specific lincRNAs modulated p53-induced apoptosis and promoted the transcription of a gene cluster. Our results suggest that p53 family members and lincRNAs constitute a complex transcriptional network involved in various biological functions and tumor suppression.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2017 2016 2015 2014 2013

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (8 results)

  • [Journal Article] Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and tumor-suppressor function.2017

    • Author(s)
      Masashi Idogawa, Tomoko Ohashi, Yasushi Sasaki, Hiroshi Nakase, Takashi Tokino
    • Journal Title

      International Joural of Cancer

      Volume: 印刷中 Issue: 12 Pages: 2785-2791

    • DOI

      10.1002/ijc.30689

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] p53 mediates the suppression of cancer cell invasion by inducing LIMA1/EPLIN.2017

    • Author(s)
      Tomoko Ohashi, Masashi Idogawa, Yasushi Sasaki, Takashi Tokino
    • Journal Title

      Cancer Letters

      Volume: 390 Pages: 58-66

    • DOI

      10.1016/j.canlet.2016.12.034

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 target.2016

    • Author(s)
      Sasaki Y, Tamura M, Takeda K, Ogi K, Nakagaki T, Koyama R, Idogawa M, Hiratsuka H, Tokino T
    • Journal Title

      Oncotarget

      Volume: VOL. 7 Issue: 38 Pages: 61426-61437

    • DOI

      10.18632/oncotarget.11366

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CRKL oncogene is downregulated by p53 through miR-200s2015

    • Author(s)
      Tamura M, Sasaki Y, Kobashi K, Takeda K, Nakagaki T, Idogawa M, Tokino T.
    • Journal Title

      CANCER SCIENCE

      Volume: 106 Issue: 8 Pages: 1033-1040

    • DOI

      10.1111/cas.12713

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model.2015

    • Author(s)
      Nakagaki S, Arimura Y, Nagaishi K, Isshiki H, Nasuno M, Watanabe S, Idogawa M, Yamashita K, Naishiro Y, Adachi Y, Suzuki H, Fujimiya M, Imai K, Shinomura Y.
    • Journal Title

      Journal of Gastoroenterology

      Volume: 50 Issue: 9 Pages: 962-74

    • DOI

      10.1007/s00535-015-1049-0

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification and analysis of large intergenic non-coding RNAs regulated by p53 family members through a genome-wide analysis of p53-binding sites2014

    • Author(s)
      Idogawa M, Ohashi T, Sasaki Y, Maruyama R, Kashima L, Suzuki H, Tokino T
    • Journal Title

      Hum Mol Genet

      Volume: 23 Issue: 11 Pages: 2847-2857

    • DOI

      10.1093/hmg/ddt673

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Array-based genome-wide RNAi screening to identify shRNAs that enhance p53-related apoptosis in human cancer cells.2014

    • Author(s)
      Idogawa M, Ohashi T, Sugisaka J, Sasaki Y, Suzuki H, Tokino T.
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 7540-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness2014

    • Author(s)
      Tamura M, Sasaki Y, Koyama R, Takeda K, Idogawa M, Tokino T
    • Journal Title

      Oncogene

      Volume: (in press) Issue: 40 Pages: 4837-4846

    • DOI

      10.1038/onc.2013.427

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal stem cells cancel azoxymethane-induced tumor initiation2014

    • Author(s)
      Nasuno M, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nakagaki S, Watanabe S, Idogawa M, Yamashita K, Naishiro Y, Adachi Y, Suzuki H, Fujimiya M, Imai K, Shinomura Y
    • Journal Title

      Stem Cells

      Volume: 32 Issue: 4 Pages: 913-925

    • DOI

      10.1002/stem.1594

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors2014

    • Author(s)
      Watanabe S, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nasuno M, Yamashita K, Idogawa M, Naishiro Y, Murata M, Adachi Y, Fujimiya M, Imai K, Shinomura Y
    • Journal Title

      J Gastroenterol

      Volume: 49 Issue: 2 Pages: 270-282

    • DOI

      10.1007/s00535-013-0901-3

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] AKR1B10, a transcriptional target of p53, is Downregulated in Colorectal Cancers Associated with Poor Prognosis2013

    • Author(s)
      Ohashi T et al.
    • Journal Title

      Mol Cancer Res

      Volume: 11 Issue: 12 Pages: 1554-1163

    • DOI

      10.1158/1541-7786.mcr-13-0330-t

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 癌におけるp53および長鎖非コードRNA(lncRNA)による転写ネットワーク解析2016

    • Author(s)
      井戸川 雅史
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] RNA-seqとChIP-seqの複合解析による非コードRNAを含むp53標的遺伝子の同定2015

    • Author(s)
      井戸川 雅史
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] ゲノム網羅的p53結合領域解析とマイクロアレイを組み合わせたp53ファミリー標的長鎖非コードRNA(lincRNA)の同定と解析2014

    • Author(s)
      井戸川 雅史
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] ゲノム網羅的p53結合領域解析とマイクロアレイを組み合わせたp53ファミリー標的長鎖非コードRNA(lincRNA)の同定と解析2014

    • Author(s)
      井戸川 雅史
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification and analysis of large intergenic non-coding RNAs regulated by p53 family members through a genome-wide analysis of p53 binding sites2014

    • Author(s)
      Masashi Idogawa
    • Organizer
      16th International p53 Workshop
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2014-06-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of novel p53 family target genes by ChIP-Seq and mRNA expression analysis combined with genome-wide p53-binding motif analysis in silico.2013

    • Author(s)
      Masashi Idogawa
    • Organizer
      6th p63/p73 International Workshop.
    • Place of Presentation
      Chiba
    • Related Report
      2013 Research-status Report
  • [Presentation] ゲノム網羅的p53結合領域解析によるp53ファミリーの転写標的となる大型介在性非コードRNA(lincRNA)の同定と機能解析2013

    • Author(s)
      井戸川 雅史
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ゲノム網羅的p53結合領域解析によるp53ファミリーの転写標的となる大型遺伝子介在性非コードRNA(lincRNA)の同定と機能解析2013

    • Author(s)
      井戸川 雅史
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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