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Roles of RNA methylation in regulation of oncogenic T-UCRs.

Research Project

Project/Area Number 18K07941
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionThe University of Tokushima

Principal Investigator

KUWANO Yuki  徳島大学, 大学院医歯薬学研究部(医学域), 講師 (00563454)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsRNA / 超保存領域 / RNAプロセシング / 大腸がん / RNAメチル化 / RNA修飾 / RNAスプライシング / 選択的スプライシング
Outline of Final Research Achievements

Ultraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138) that spans exon 2 and its neighboring introns. Uc.138 is upregulated in colon cancer cell lines, although it is not translated to Tra2β protein because of its nuclear retention. Nevertheless, the clinical significance and biological functions of uc.138 in colon cancer cells remain unclear. In this study, RNA in situ hybridization showed that uc.138 was predominantly overexpressed in the nucleus of colon adenocarcinoma and adenoma. Overexpression of uc.138 in colon cancer cells promoted cell proliferation by changing the expression of G2/M-related cell cycle regulators.Uc.138 plays an oncogenic role in tumor progression and may become a potential biomarker and therapeutic target in colon cancer.

Academic Significance and Societal Importance of the Research Achievements

超保存領域(UCR)はマウス以上の高等生物のみ進化の過程で獲得したゲノム配列であるが、その生理学的意義は不明である。UCRから転写されるRNA群(T-UCR)の発現異常は、がんを含めた高等生物の複雑な細胞恒常性の破綻を判定するRNAバイオマーカーと成りうる。
UCRの多くはタンパク質をコードしておらず、一部のT-UCRはがん悪性化とともに核への蓄積が認められることから、T-UCRの配列特異的なノックダウンは、正規タンパク質の発現に影響を与えず、新しいコンセプトの核酸医療の開発に繋がる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP22020

    • Author(s)
      Nishida Kensei、Kuwano Yuki、Rokutan Kazuhito
    • Journal Title

      Cancers

      Volume: 12 Issue: 1 Pages: 174-174

    • DOI

      10.3390/cancers12010174

    • NAID

      120006783218

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth2019

    • Author(s)
      Saijo Saki、Kuwano Yuki、Tange Shoichiro、Rokutan Kazuhito、Nishida Kensei
    • Journal Title

      BMC Cancer

      Volume: 19 Issue: 1

    • DOI

      10.1186/s12885-019-5715-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells2019

    • Author(s)
      Nishikawa Tatsuya、Kuwano Yuki、Takahara Yumiko、Nishida Kensei、Rokutan Kazuhito
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10276-10276

    • DOI

      10.1038/s41598-019-46659-x

    • NAID

      120006732015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nucleolin facilitates nuclear retention of an ultraconserved region containing <i>TRA2B</i> and accelerates colon cancer cell growth2018

    • Author(s)
      Satake Yuzuru、Kuwano Yuki、Nishikawa Tatsuya、Fujita Kinuyo、Saijo Saki、Itai Miki、Tanaka Hiroki、Nishida Kensei、Rokutan Kazuhito
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 42 Pages: 26817-26833

    • DOI

      10.18632/oncotarget.25510

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diverse roles of RNA-binding proteins in cancer traits and their implications in gastrointestinal cancers.2018

    • Author(s)
      Masuda K, Kuwano Y.
    • Journal Title

      Wiley Interdiscip Rev RNA.

      Volume: 10 Issue: 3

    • DOI

      10.1002/wrna.1520

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The transcribed ultraconserved region uc.138 accelerates colon cancer progression2020

    • Author(s)
      桑野由紀、西田憲生、六反一仁
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 超保存領域を内在するT-UCRのRNAメチル化を介した大腸がん悪性化機構2019

    • Author(s)
      桑野由紀、西田憲生、六反一仁
    • Organizer
      第42回日本分子生物学会年会 (福岡)
    • Related Report
      2019 Research-status Report
  • [Presentation] Nuclear retention of transcribed ultraconserved region uc.138 promotes colon cancer cell growth2019

    • Author(s)
      Y. Kuwano, K. Nishida, Y. Satake, K. Rokutan
    • Organizer
      Cell Symposium-Regulatory RNAs (Berlin, Germany)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 機能性RNA TRA2 b 4の核局在が誘導する大腸がん悪性化メカニズム2018

    • Author(s)
      Y. Kuwano, T. Nishikawa, S. Saijo, K. Nishida, K. Rokutan
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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