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Role of DNA damage-induced directional LINE-1-retrotransposition in tumor progression.

Research Project

Project/Area Number 18K06191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionHamamatsu University School of Medicine (2020-2021)
Nagoya University (2018-2019)

Principal Investigator

IIJIMA Kenta  浜松医科大学, 光尖端医学教育研究センター, 研究技術職員 (20565626)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsLINE-1 / DNA損傷 / がん化 / 発がん / DNA損傷応答 / 細胞老化 / レトロトランスポゾン
Outline of Final Research Achievements

Retrotransposition of Long interspersed element-1 (LINE-1) is induced by various stimuli, however, the precise mechanism and its biological roles remain unknown. The improvement of analysis to comprehensively identify the de novo integrations of LINE-1 showed the unexpectedly higher frequencies in tumor tissues, implying the intimate association of tumor progression and LINE-1 retrotransposition. In this study, we found that LINE-1-integration directed to a specific region was provoked by DNA damage induction. The interaction between LINE-1 protein complex and transcriptional factors , which response to DNA damage and accumulate on the target genes underlay the region directional LINE-1 retrotransposion.

Academic Significance and Societal Importance of the Research Achievements

本研究ではDNA損傷により誘導される部位特異的なLINE-1転移誘導機構、および選択的な細胞形質変化の可能性を明らかにした。本研究成果は基礎生物学のみにとどまらず、医薬学領域にも広範な影響をもたらす。すなわち、LINE-1の活性化状態により疾患のリスク評価に応用できる可能性、あるいはLINE-1活性の適切な制御を可能とする新規薬剤の開発により、がんをはじめとした疾患の予防・治療が可能となると期待され、本研究によりもたらされる知見は今後の医療・創薬分野における新たな創造的基盤をもたらすものと予想される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] The functional analysis of DNA damage induced LINE-1 retrotranspositon2019

    • Author(s)
      Kenta Iijima, Yutaka Kondo, Yukihito Ishizaka
    • Organizer
      Abcam Epigenetics Conference and 14th Asia Epigenome Meeting / 3rd Taipei Epigenetics and Chromatin Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 内在性レトロエレメントLINE-1のDNA損傷による転移活性化機構2019

    • Author(s)
      飯島健太、近藤豊、石坂幸人
    • Organizer
      第13回日本エピジェネティクス研究会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 内在性レトロエレメントLINE-1の選択的転移による発がん制御機構2018

    • Author(s)
      飯島健太、石坂幸人
    • Organizer
      日本放射線影響学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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