Regulatory mechanisms of miRNA biogenesis which is involved in tumorigenesis for approach to cancer therapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15601
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kochi University
• 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)
• 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
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: RNA結合タンパク質 / miRNA / NF90 / がん / RNA二次構造

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.

Free Research Field

分子生物学

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。