Long non-coding RNA as an epigenetic modulator in cancer cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03582
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Nagoya University
• Principal Investigator: Kondo Yutaka 名古屋大学, 医学系研究科, 教授 (00419897)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 非翻訳RNA / エピゲノム / 膠芽腫 / ドラッグデリバリーシステム

Outline of Final Research Achievements

We identified that TUG1 (taurine upregulated gene 1) is an indispensable long noncoding RNA (lncRNA) to regulate intrinsic DNA replication stress (RS)/ DNA repair in cancer cells. When replication was disrupted, the ATR signaling pathway was activated and immediately induced transcription of TUG1. Mechanistically, TUG1 promoted recruitment of replication protein A (RPA) to the replication forks. Our data reveal a novel spatiotemporal role of TUG1 as an indispensable molecule to relieve RS in cancer cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach for cancer treatment.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

難治性腫瘍は根治がほぼ期待できないため患者本人や家族の苦痛、そして社会的損失が計り知れない。今回、TUG1に対して核酸医薬の開発を進めるための基盤的データが構築てきた。TUG1に対する核酸医薬開発は、独自の分子基盤に基づいた治療薬が期待でき、実用化ができれば国内のみならず他国の開発と比しても極めて競争力が高いと考える。また既存のがん治療法とは作用機序が異なることから他の既存治療法を強化する新たな治療戦略の開発にもつながる。