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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Hamamatsu 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
• Keywords: LINE-1 / DNA損傷 / がん化

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.

Free Research Field

ウィルス学

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。