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Mechanism of colorectal tumorigenesis caused by lncRNA-Transcription factor complex

Research Project

Project/Area Number 15K08299
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Taniue Kenzui  東京大学, 分子細胞生物学研究所, 助教 (90648627)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsASBEL / TCF3 / ATF3 / β-catenin / 大腸癌 / 腫瘍形成能 / アンチセンスRNA / lncRNA / 癌
Outline of Final Research Achievements

Wnt/β-catenin signaling plays a key role in the tumorigenicity of colon cancer. Furthermore, it has been reported that lncRNAs are dysregulated in several steps of cancer development. Here we show that β-catenin directly activates the transcription of the lncRNA ASBEL (antisense ncRNA in the ANA/BTG3) and the transcription factor TCF3, both of which are required for the survival and tumorigenicity of colorectal cancer cells. ASBEL interacts with and recruits TCF3 to ATF3 locus, where it represses the expression of ATF3. Furthermore, we demonstrate that ASBEL-TCF3-mediated down-regulation of ATF3 expression is required for the proliferation and tumorigenicity of colon tumor cells. Our results reveal a pathway involving an lncRNA and two transcription factors that plays a key role in Wnt/β-catenin-mediated tumorigenesis. Our results suggest that the β-catenin-ASBEL-TCF3-ATF3 pathway may be a promising target for the therapy of colon cancer.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (24 results)

All 2018 2017 2016 2015 Other

All Journal Article (8 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Book (3 results) Remarks (4 results)

  • [Journal Article] PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for monitoring ovarian clear cell carcinoma.2018

    • Author(s)
      Morikawa A., Hayashi T., Shimizu N., Kobayashi M., Taniue K., Takahashi A., Tachibana K., Saito M., Kawabata A., Iida Y., Ueda K., Saito M., Yanaihara N., Tanabe H., Yamada K., Takano H., Nureki O., Okamoto A. and Akiyama T.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 20 Pages: 15266-15274

    • DOI

      10.18632/oncotarget.24555

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASBEL-TCF3 complex is required for the tumorigenicity of colorectal cancer cells.2016

    • Author(s)
      Taniue K, Kurimoto A, Takeda Y, Nagashima T, Okada-Hatakeyama M, Yuki K, Katsuhiko S, Akiyama T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 113 Issue: 45 Pages: 12739-12744

    • DOI

      10.1073/pnas.1605938113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1.2016

    • Author(s)
      Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, Nagashima T, Okada-Hatakeyama M, Oyama M, Kozuka-Hata H, Hiyoshi M, Kitayama J, Negishi L, Kawasaki Y, Akiyama T.
    • Journal Title

      Proceedings of the National Academy of Sciences U S A.

      Volume: 113 Issue: 5 Pages: 1273-8

    • DOI

      10.1073/pnas.1500992113

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] がん診断の新たなマテリアル, ctDNA2016

    • Author(s)
      西塚哲、谷上賢瑞、八谷剛史、中川英刀
    • Journal Title

      実験医学 2016年4月号

      Volume: 34 Pages: 948-952

    • Related Report
      2015 Research-status Report
  • [Journal Article] 臨床現場からctDNAサンプル抽出まで2016

    • Author(s)
      谷上賢瑞、八谷剛史、西塚哲、中川英刀
    • Journal Title

      実験医学 2016年5月号

      Volume: 34 Pages: 1319-1324

    • Related Report
      2015 Research-status Report
  • [Journal Article] Susceptibility to proteases of anti-Tn-antigen MLS128 binding glycoproteins expressed in human colon cancer cells2015

    • Author(s)
      Oura, F., Yajima, Y., Nakata, M., Taniue, K., Akiyama, T., Nakada, H., Yamamoto, K., Fujita-Yamaguchi, Y
    • Journal Title

      BioScience Trends

      Volume: 9 Issue: 1 Pages: 49-55

    • DOI

      10.5582/bst.2014.01127

    • NAID

      130005054681

    • ISSN
      1881-7815, 1881-7823
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells2015

    • Author(s)
      Hironobu Sugimasa, Kenzui Taniue, Akiko Kurimoto, Yasuko Takeda, Yoshihiro Kawasaki, Tetsu Akiyama
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: Volume 459, Issue 1 Issue: 1 Pages: 29-35

    • DOI

      10.1016/j.bbrc.2015.02.043

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RNA-seqを用いたlncRNAの同定2015

    • Author(s)
      谷上賢瑞
    • Journal Title

      実験医学増刊 ノンコーディングRNAテキストブック

      Volume: 33 Pages: 176-182

    • Related Report
      2015 Research-status Report
  • [Presentation] Colorectal cancer and long ncRNA2017

    • Author(s)
      谷上 賢瑞
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 大腸がんと長鎖ノンコーディングRNA2017

    • Author(s)
      谷上 賢瑞
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The ASBEL-TCF3 complex is required for the tumorigenicity of colorectal cancer cells2016

    • Author(s)
      Kenzui Taniue, Yasuko Takeda, Tetsu Akiyama
    • Organizer
      2016 the American Society for Cell Biology Annual Meeting
    • Place of Presentation
      San Francisco(米国)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] β-catenin-mediated upregulation of the ASBEL-TCF3 complex is critical for colorectal tumorigenesis2016

    • Author(s)
      Kenzui Taniue, Tetsu Akiyama
    • Organizer
      The 39th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF12016

    • Author(s)
      谷上 賢瑞
    • 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)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF12016

    • Author(s)
      Kenzui Taniue, Yasuko Takeda, Tetsu Akiyama
    • Organizer
      American Association for Cancer Research Annual Meeting 2016
    • Place of Presentation
      New Orleans(米国)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF12016

    • Author(s)
      Kenzui Taniue, Yasuko Takeda, Tetsu Akiyama
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2016-04-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF12015

    • Author(s)
      Kenzui Taniue, Yasuko Takeda, Tetsu Akiyama
    • Organizer
      AACR meeting 『Noncoding RNAs and Cancer』
    • Place of Presentation
      Boston, Massachusetts, USA
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF12015

    • Author(s)
      Kenzui Taniue, Akiko Kurimoto, Hironobu Sugimasa, Yasuko Takeda, Tetsu Akiyama
    • Organizer
      H27年度 第1回分生研研究交流会
    • Place of Presentation
      東京大学 弥生講堂一条ホール(東京都・文京区)
    • Year and Date
      2015-06-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] 実験医学 【速報】いま、がんのクリニカルシークエンスがおもしろい!第1回 がん診断の新たなマテリアル,ctDNA2016

    • Author(s)
      西塚 哲, 谷上 賢瑞, 八谷 剛史, 中川 英刀
    • Total Pages
      5
    • Publisher
      羊土社
    • Related Report
      2016 Research-status Report
  • [Book] 実験医学【速報】いま、がんのクリニカルシークエンスがおもしろい!第2回 臨床現場からctDNAサンプル抽出まで2016

    • Author(s)
      西塚 哲, 谷上 賢瑞, 八谷 剛史, 中川 英刀
    • Total Pages
      5
    • Publisher
      羊土社
    • Related Report
      2016 Research-status Report
  • [Book] 実験医学【速報】いま、がんのクリニカルシークエンスがおもしろい!第3回 ctDNA解析技術:検出感度と網羅性2016

    • Author(s)
      西塚 哲, 谷上 賢瑞, 八谷 剛史, 中川 英刀
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2016 Research-status Report
  • [Remarks] 東大、長鎖ノンコーディングRNAが制御する新たな大腸がん化のメカニズムを解明

    • URL

      http://release.nikkei.co.jp/detail.cfm?relID=425688&lindID=5

    • Related Report
      2016 Research-status Report
  • [Remarks] 長鎖ノンコーディング RNA が制御する新たな大腸がん化のメカニズム

    • URL

      http://www.iam.u-tokyo.ac.jp/wordpress/wp-content/uploads/2016/10/pressrelease_281018.pdf

    • Related Report
      2016 Research-status Report
  • [Remarks] 大腸がんの発症に重要な長いノンコーディングRNAの発見

    • URL

      http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/identification-of-long-non-coding-RNA-critical-for-development-of-colorectal-cancer.html

    • Related Report
      2016 Research-status Report
  • [Remarks]

    • URL

      http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/identification-of-long-non-coding-RNA-critical-for-development-of-colorectal-cancer.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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