Regulatory mechanisms of miRNA biogenesis which is involved in tumorigenesis for approach to cancer therapy
| Project/Area Number |
17K15601
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Kochi University |
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Principal Investigator |
HIGUCHI Takuma 高知大学, 教育研究部医療学系基礎医学部門, 助教 (10754567)
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| Research Collaborator |
SAKAMOTO Shuji 高知大学, 教育研究部医療学系基礎医学部門, 准教授
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | RNA結合タンパク質 / miRNA / NF90 / がん / RNA二次構造 / フィードバックループ / microRNA / NF45 / マイクロRNA / デコイRNA |
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| Outline of Final Research Achievements |
(1) Nuclear Factor 90 (NF90), which is double stranded RNA binding protein, and NF45 form a heterodimer complex (NF90-NF45). In cancer tissues, NF90-NF45 is known to bind to primary miRNAs (pri-miRNAs), resulting in an inhibition of anti-oncogenic miRNA biogenesis. However, a common characteristic of pri-miRNA for NF90 binding motif is still unclear. In this study, we found that NF90 preferentially binds to pri-miRNAs that have a structure of straight stem with few mismatches.
(2) We demonstrated that miR-7, an anti-oncogenic miRNA, regulates the expression of NF90. Taken together with our previously findings that NF90-NF45 suppresses miR-7 biogenesis, it suggests that the level of NF90 is increased by a negative feedback loop between NF90 and miR-7 in tumor tissues under physiological conditions.
Based on (1) and (2), we would expect to be applied oligo RNAs, which have a NF90 binding motif, and miR-7 to cancer therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
NF90とNF45の複合体はがん部で高く発現しており、がん抑制作用を有する複数のmiRNAの生合成を阻害している。本研究の成果より、NF90の結合するpri-miRNAの構造が同定できたため、その情報を元に、内在性pri-miRNAよりもNF90-NF45に対して結合性の高いオリゴヌクレオチド (デコイRNA)を作製することが可能となった。デコイRNAはNF90-NF45のmiRNA生合成阻害機能を抑える効果が期待できるため、新規のがん治療法開発の礎となることが想定される。
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Report
(3 results)
Research Products
(22 results)
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[Journal Article] An NF90/NF110-Mediated Feedback Amplification Loop Regulates DICER Expression and Controls Ovarian Carcinoma Progression.2018
Author(s)
Barbier J, Chen X, Sanchez G, Cai M, Helsmoortel M, Higuchi T, Giraud P, Contreras X, Yuan G, Feng Z, Nait-Saidi R, Deas O, Bluy L, Judde JG, Rouquier S, Ritchie W, Sakamoto S, Xie D, and Kiernan R
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Journal Title
Cell Research
Volume: 28
Issue: 5
Pages: 556-571
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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