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Identification of microRNA and epigenome abnormality in colorectal cancer based on molecular subtype

Research Project

Project/Area Number 16K07145
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NOSHO KATSUHIKO  札幌医科大学, 医学部, 講師 (10597339)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsEZH2 / microRNA / 大腸癌 / microRNA-31 / IL-6 / バイオマーカー / ヒストン / エピゲノム / 分子標的治療
Outline of Final Research Achievements

MicroRNAs can function as oncogenes or tumour suppressors. Therefore, they have been increasingly recognized as useful biomarkers for various human cancers. With regard to colorectal cancers (CRCs), using miRNA array analysis, we recently discovered that microRNA-31 (miR-31) expression is significantly up-regulated in BRAF-mutated colorectal cancers (CRCs) compared with that in wild-type CRCs. Moreover, associations were identified between miR-31 expression, proximal tumor location and poor prognosis for CRCs. Moreover, the results of functional analysis showed that miR-31 may regulate BRAF activation and that the oncogenic role of miR-31 and its possibility of therapeutic target in CRCs. Thus, our current data suggest that miR-31 may be a diagnostic biomarker and therapeutic target in CRC. These novel data may lead to the establishment of a new therapeutic target or a theranostic procedure in gastroenterological cancers.

Academic Significance and Societal Importance of the Research Achievements

今回、我々は大腸癌においてEZH2がmiR-31の発現を制御することを世界で初めて明らかにした。癌の発育進展に関わるmicroRNAを制御するポリコームタンパク阻害剤やHDAC阻害剤、DNA 脱メチル化酵素などを同定することは新たな治療方法を開発できる可能性があるため、今後も本研究をさらに発展させたいと考えている。

Report

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

    (14 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Int'l Joint Research] Dana-Farber Cancer Institute(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] MicroRNA-31 reflects IL-6 expression in cancer tissue and is related with poor prognosis in bile duct cancer2018

    • Author(s)
      Ishigami Keisuke、Nosho Katsuhiko、Koide Hideyuki、Kanno Shinichi、Mitsuhashi Kei、Igarashi Hisayoshi、Shitani Masahiro、Motoya Masayo、Kimura Yasutoshi、Hasegawa Tadashi、Kaneto Hiroyuki、Takemasa Ichiro、Suzuki Hiromu、Nakase Hiroshi
    • Journal Title

      Carcinogenesis

      Volume: 39 Issue: 9 Pages: 1127-1134

    • DOI

      10.1093/carcin/bgy075

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression2018

    • Author(s)
      Eto T, Miyake K, Nosho K, Ohmuraya M, Imamura Y, Arima K, Kanno S, Fu L, Kiyozumi Y, Izumi D, Sugihara H, Hiyoshi Y, Miyamoto Y, Sawayama H, Iwatsuki M, Baba Y, Yoshida N, Furukawa T, Araki K, Baba H, Ishimoto T
    • Journal Title

      The Journal of Pathology

      Volume: 245 Issue: 4 Pages: 445-455

    • DOI

      10.1002/path.5098

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic mechanisms of immune evasion in colorectal cancer.2018

    • Author(s)
      Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ, Quist M, Nowak JA, Nishihara R, Qian ZR, Inamura K, Morikawa T, Nosho K, et al.
    • Journal Title

      Cancer Discov.

      Volume: 印刷中 Issue: 6 Pages: 730-749

    • DOI

      10.1158/2159-8290.cd-17-1327

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] EZH2 expression is a prognostic biomarker in patients with colorectal cancer treated with anti-EGFR therapeutics2017

    • Author(s)
      Yamamoto I, Nosho K, et al.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 11 Pages: 17810-17818

    • DOI

      10.18632/oncotarget.14863

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer2017

    • Author(s)
      Kanno S, Nosho K, et al.
    • Journal Title

      Carcinogenesis

      Volume: 38 Issue: 4 Pages: 425-431

    • DOI

      10.1093/carcin/bgx013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway.2016

    • Author(s)
      Kurihara H, Maruyama R, Ishiguro K, Kanno S, Yamamoto I, Ishigami K, Mitsuhashi K, Igarashi H, Ito M, Tanuma T, Sukawa Y, Okita K, Hasegawa T, Imai K, Yamamoto H, Shinomura Y, Nosho K.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 11 Pages: 12704-12717

    • DOI

      10.18632/oncotarget.7260

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The relation with tumor EZH2 expression and survival in colorectal cancer patients treated with anti-EGFR therapeutics2019

    • Author(s)
      Katsuhiko Nosho、Itaru Yamamoto、Hisayoshi Igarashi、Shinichi Kanno、Kei Mitsuhashi、Keisuke Ishigami、Hiroyoshi Kurihara、Hiroshi Nakase
    • Organizer
      11th AACR-JCA Joint Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大腸癌におけるバイオマーカーおよび治療標的としての幹細胞関連転写因子PRDM14の意義2018

    • Author(s)
      五十嵐央祥、能正勝彦、仲瀬裕志
    • Organizer
      JDDW2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 消化器癌のmicroRNA・エピゲノム異常の解明と発癌におけるmicrobiotaの役割2018

    • Author(s)
      能正勝彦
    • Organizer
      第29回日本消化器癌発生学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Serrated pathwayから発生する大腸癌の分子異常を利用した分子診断・個別化治療の可能性と腸内細菌の関与2018

    • Author(s)
      能正勝彦
    • Organizer
      第55回日本癌治療学会学術集会イブニングセミナー 7
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 大腸癌におけるEZH2発現とエピゲノム異常との関連の検討と抗EGFR抗体薬の効果予測バイオマーカーとしての可能性2017

    • Author(s)
      能正 勝彦
    • Organizer
      第13回日本消化管学会総会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2017-02-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 高齢者大腸癌の臨床・分子生物学的特徴を利用した癌予防の治療戦略2017

    • Author(s)
      能正 勝彦
    • Organizer
      第92回北海道腸疾患研究会
    • Place of Presentation
      札幌
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 大腸癌におけるポリコーム蛋白EZH2発現と分子異常・生命予後との関連とmicroRNA-31の制御機構2016

    • Author(s)
      能正 勝彦
    • Organizer
      第27回日本消化器癌発生学会総会
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島市)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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