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2023 Fiscal Year Final Research Report

Comprehensive validation of circulating microRNA signatures for Moyamoya disease early detection as an epigenome blood biomarker

Research Project

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Project/Area Number 19H03765
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionHokkaido University

Principal Investigator

Ito Masaki  北海道大学, 大学病院, 助教 (10399850)

Co-Investigator(Kenkyū-buntansha) 藤村 幹  北海道大学, 医学研究院, 教授 (00361098)
内野 晴登  北海道大学, 大学病院, 特任助教 (40775144)
佐藤 典宏  北海道大学, 大学病院, 教授 (50360912)
矢部 一郎  北海道大学, 医学研究院, 教授 (60372273)
杉山 拓  北海道大学, 大学病院, 講師 (70748863)
寳金 清博  北海道大学, -, 総長 (90229146)
中山 若樹  北海道大学, 医学研究院, 客員研究員 (40421961)
数又 研  北海道大学, 大学病院, 講師 (60634144)
東海林 菊太郎  北海道大学, 大学病院, 医員 (70883164)
浜内 祝嗣  北海道大学, 医学研究院, 助教 (70794387)
Project Period (FY) 2019-04-01 – 2024-03-31
KeywordsMoyamoya disease / circulating microRNA / blood biomarker / epigenome / angiogenesis / pial synangiosis
Outline of Final Research Achievements

We hypothesized that circulating microRNAs might play a role in epigenetic regulation in the pathogenesis of Moyamoya disease (MMD), given that RNF213 gene fails to account for its full spectrum of clinical presentations. In this study, we quantified plasma microRNA expression using quantitative PCR panels and compared it between two groups: MMD (n=82) and age/sex-matched healthy controls (n=78). Principal component analysis revealed distinct differences in the plasma microRNA expression profiles between the two groups. Differential expression analysis identified significant changes in three microRNA entities, including hsa-miR-328-3p. The plasma expression level of miR-328-3p was significantly associated with clinical features, including onset age, sex, angiographical disease stage, PCA involvement, and RNF213 p.R4810K. Moreover, significant expression of miR-328-3p was confirmed in the arachnoid membrane in MMD. Therefore, plasma microRNAs may serve as epigenetic regulators in MMD.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

もやもや病は、疾患感受性遺伝子RNF213をはじめとする遺伝的背景に、さまざまな二次的環境要因、すなわち、細菌またはウィルス感染症、自己免疫性疾患・自己抗体、放射線被曝などの環境要因が作用して発症すると考えられてきた。この研究によりもやもや病の発症素因を修飾する病態修飾因子として、エピゲノム遺伝子発現制御機構が血漿中や大脳くも膜上で作用していることが示唆された。本研究成果は、もやもや病の分子病態を明らかにするための基盤的研究成果となるだろう。

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Published: 2025-01-30  

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