Perturbation of homologous recombination repair in tumor through inhibition of lncRNA function
| Project/Area Number |
18K15293
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Okamoto Yuka 公益財団法人がん研究会, がん化学療法センター ゲノム研究部, 研究員 (50625217)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | lncRNA / 相同組換え修復 / DNA相同組換え修復 / 核酸医薬 |
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| Outline of Final Research Achievements |
Homologous recombination (HR) repair is considered to be an intriguing target for tumor therapy. However, development of effective molecular-targeted therapy is still in progress and target candidates with high tumor-specificity is required. This research was aimed to identify long non-coding (lnc) RNA target involved in HR repair in tumor. As a result of several screening and transcriptome analysis, multiple lncRNA targets were identified. Inhibition of these targets by knockdown in cultured human tumor cells resulted in deficiency of HR repair, growth inhibition and sensitization to cisplatin.
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| Academic Significance and Societal Importance of the Research Achievements |
HR修復を標的とし、RAD51のDNA結合阻害剤、HR応答の上流であるATM・ATR・CHK1阻害剤といった化合物がこれまでに報告され、臨床開発に進んでいるが、必ずしも特異性が高くない。本研究で、HR修復機能維持に関与するlncRNAを複数同定できたことにより、HR修復を標的とした新たな分子標的候補を見出せた。また現在までに、5-60,000遺伝子存在すると考えられているが、その殆どについては機能未知であるlncRNAについて、新たな生物学的知見が得られた。
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Report
(3 results)
Research Products
(6 results)
