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Transcribed-ultraconserved regions regulate cellular senescence and proliferation of conlon cancer.

Research Project

Project/Area Number 26713027
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Gastroenterology
Research InstitutionThe University of Tokushima

Principal Investigator

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

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2015: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords非コードRNA / RNAプロセシング / 大腸がん / 超保存領域 / 癌 / 発現制御 / 遺伝子 / マイクロアレイ / 癌悪性化 / 安定過剰発現細胞
Outline of Final Research Achievements

Ultraconserved regions (UCRs) are >200-bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood.
The transformer 2β (TRA2B) exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2β4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2β4 knockdown stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells. TRA2β4 interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop structure of exon 2. These results suggest that TRA2β4 may sequester Sp1 from occupying promoters of target genes including CDKN1A, promoting cell growth by interrupting the senescence-related gene expression program.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome2016

    • Author(s)
      Kuwano Y, Nishida K, Akaike Y, Kurokawa K, Nishikawa T, Masuda K, Rokutan K
    • Journal Title

      Int J Mol Sci

      Volume: 17 Issue: 10 Pages: 10-10

    • DOI

      10.3390/ijms17101638

    • NAID

      120006535037

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serine/arginine-rich splicing factor 7 regulates p21-dependent growth arrest in colon cancer cells2016

    • Author(s)
      Saijo S, Kuwano Y, Masuda K, Nishikawa T, Rokutan K, Nishida K
    • Journal Title

      J Med Invest

      Volume: 63 Issue: 3.4 Pages: 219-226

    • DOI

      10.2152/jmi.63.219

    • NAID

      130005245836

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultraconserved region-containing Transformer 2β4 controls senescence of colon cancer cells2015

    • Author(s)
      Kajita K, Kuwano Y, Satake Y, Kano S, Kurokawa K, Akaike Y, Masuda K, Nishida K, Rokutan K
    • Journal Title

      Oncogenesis

      Volume: - Issue: 4 Pages: e213-e213

    • DOI

      10.1038/oncsis.2016.18

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transformer 2β and miR-204 regulate apoptosis through competitive binding to 3’UTR of BCL2 mRNA.2015

    • Author(s)
      Kuwano Y, Nishida K, Kajita K, Satake Y, Akaike Y, Fujita K, Kano S, Masuda K, Rokutan K.
    • Journal Title

      Cell Death Differ.

      Volume: 22 (5) Issue: 5 Pages: 815-825

    • DOI

      10.1038/cdd.2014.176

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homeodomain-interacting protein kinase 2 regulates DNA damage response through interacting with heterochromatin protein 1γ.2014

    • Author(s)
      Akaike Y, Kuwano Y, Nishida K, Kurokawa K, Kajita K, Kano S, Masuda K, Rokutan K.
    • Journal Title

      Oncogene.

      Volume: - Issue: 26 Pages: 3463-3473

    • DOI

      10.1038/onc.2014.278

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HuR regulates alternative splicing of the TRA2 β gene in human colon cancer cells under oxidative stress.2014

    • Author(s)
      Akaike Y, Masuda K, Kuwano Y, Nishida K, Kajita K, Kurokawa K, Satake Y, Shoda K, Imoto I, Rokutan K.
    • Journal Title

      Mol Cell Biol

      Volume: 34 Issue: 15 Pages: 2857-73

    • DOI

      10.1128/mcb.00333-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Ultraconserved region-containing transformer 2β4 associates with nucleolin and regulates cellular proliferation.2017

    • Author(s)
      Kuwano Y, Satake Y, Nishikawa T, Fujita M, Saijo S, Nishida K, Rokutan K.
    • Organizer
      Protein-RNA Interactions: Keystone symposia
    • Place of Presentation
      Banff (Canada)
    • Year and Date
      2017-02-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serine/arginine-richスプライシング因子SRSFを介したエピジェネティック調節機構2016

    • Author(s)
      桑野由紀、西田憲生、西川達哉、六反一仁
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県、横浜市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Ultraconserved regionを内在するTRA2β4の発現制御と大腸がんの細胞増殖メカニズムの解明2016

    • Author(s)
      西川達哉、桑野 由紀、小玉 美幸、西條早希、田中 裕基、板井 美樹、藤田 絹代、西田 憲生、六反 一仁
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県、横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Ultraconserved regionを内在するTRA2β4を介した細胞周期調節メカニズムの解析2015

    • Author(s)
      小玉美幸、桑野由紀、佐竹譲、狩野静香、藤田絹代、板井美樹、田中裕基、千葉美穂、西田憲生、六反一仁
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド (兵庫県・神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] TRA2β4とnucleolinの相互作用を介した大腸癌細胞増殖メカニズムの解明2015

    • Author(s)
      佐竹譲、桑野由紀、狩野静香、藤田絹代、板井美樹、田中裕基、西田憲生、六反一仁
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド (兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ultraconserved region-containing transformer 2β4 inhibits senesces of colon cancer cells.2015

    • Author(s)
      Kuwano Y, Kajita K, Kano S, Satake Y, Fujita M, Itai M, Nishida K, Rokutan K.
    • Organizer
      Cell symposia-Human genomics
    • Place of Presentation
      Singapore (Singapore)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規非コードRNA TRA2β4を介した大腸がん悪性化の分子基盤2015

    • Author(s)
      桑野由紀、佐竹譲、狩野静香、藤田絹代、西田憲生、六反一仁
    • Organizer
      第10回臨床ストレス応答学会
    • Place of Presentation
      東京農工大(東京都・小金井市)
    • Year and Date
      2015-11-06
    • Related Report
      2015 Annual Research Report
  • [Presentation] ストレス応答性マイクロRNAを介した遺伝子発現調節2015

    • Author(s)
      桑野由紀、六反一仁
    • Organizer
      第56回日本心身医学会学術総会ならびに学術講演会
    • Place of Presentation
      タワーホール船橋(東京都・江戸川区)
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 非コードRNA(T-UCR)を介した大腸がんの細胞増殖メカニズムの検討2014

    • Author(s)
      桑野由紀、梶田啓介、佐竹謙、狩野静香、藤田絹代、板井美樹、西田憲生、成戸卓也、六反一仁
    • Organizer
      第9回臨床ストレス応答学会
    • Place of Presentation
      マスカットキューブ (岡山県、岡山市)
    • Year and Date
      2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of functional transcribed-ultraconserved regions of SR protein family.2014

    • Author(s)
      Kano S, Nishida K, Satake Y, Fujita K, Itai M, Naruto T, Masuda K, Kuwano Y, Rokutan K.
    • Organizer
      Cell symposia-Regulatroy RNAs
    • Place of Presentation
      Berkeley, California, U.S.A
    • Year and Date
      2014-10-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Transformer 2b and miR-204 regulate cell death through competitive binding to 3’UTR of BCL2 mRNA.2014

    • Author(s)
      Kuwano Y, Satake S, Kano S, Fujita M, Itai M, Nishida K, Naruto T, Masuda K, Rokutan K.
    • Organizer
      Cell symposia-Regulatroy RNAs
    • Place of Presentation
      Berkeley, California, U.S.A
    • Year and Date
      2014-10-19
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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