Long non-coding RNA as an epigenetic modulator in cancer cells
| Project/Area Number |
17H03582
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Nagoya University |
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Principal Investigator |
Kondo Yutaka 名古屋大学, 医学系研究科, 教授 (00419897)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| 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 / エピジェネティクス / 長鎖非翻訳ＲＮＡ / がん / TUG1 / メチル化 |
|---|
| 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.
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| 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。
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant.2020
Author(s)
Maeda S, Ohka F, Okuno Y, Aoki K, Motomura K, Takeuchi K, Kusakari H, Yanagisawa N, Sato S, Yamaguchi J, Tanahashi K, Hirano M, Kato A, Shimizu H, Kitano Y, Yamazaki S, Yamashita S, Takeshima H, Shinjo K, Kondo Y, Wakabayashi T, Natsume A.
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Journal Title
Acta Neuropathologica Communications
Volume: 8
Issue: 1
Pages: 8-19
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] DNA methylation inhibitor attenuates polyglutamine-induced neurodegeneration by regulating Hes52019
Author(s)
Kondo N, Tohnai G, Sahashi K, Iida M, Kataoka M, Nakatsuji H, Tsutsumi Y, Hashizume A, Adachi H, Koike H, Shinjo K, Kondo Y, Sobue G, Katsuno M.
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Journal Title
EMBO Mol Med
Volume: none
Issue: 5
DOI
Related Report
Peer Reviewed / Open Access
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[Book] 医学のあゆみ2018
Author(s)
勝島啓佑、鈴木美穂、近藤 豊
Total Pages
70
Publisher
医歯薬出版株式会社
Related Report
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