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Determination of the serum miRNA expression profile in human moyamoya disease (MMD)

ABSTRACT: Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. However, the etiology of this rare disease remains widely unknown. Serum microRNA (miRNA) profiles have been screened to identify novel biomarkers for disease diagnosis and prognosis. Here, we identified important serum miRNAs that might play important roles in contributing to MMD pathogenesis through microarray analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE45737 | GEO | 2013/04/04

SECONDARY ACCESSION(S): PRJNA196151

REPOSITORIES: GEO

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Project description:We aim to investigate circulating genome-wide microRNA (miRome) profiles in Moyamoya disease (MMD)-discordant monozygotic (MZ) twins with the RNF213 founder mutation (rs112735431).A disease discordant monozygotic twin-based study design may unmask potential confounders from previously published circulating microRNA signature in MMD. Circulating genome-wide microRNA (miRNome) profiling was performed in MMD-discordant monozygotic twins, non-twin-MMD patients, and non-MMD healthy volunteers by microarray followed by qPCRvalidation, using blood samples. Differential plasma-microRNAs were further quantified in endothelial cells differentiated from iPS cell lines (iPSECs) derived from another independent non-twin cohort. Lastly, their target gene expression in the iPSECs was analyzed. Microarray detected 309 plasma-microRNAs in MMD-discordant monozygotic twins that were also detected in the non-twin cohort. Principal component analysis of the plasma-microRNA expression level demonstrated distinct 2 groups separated by MMD and healthy control in the twin- and non-twin cohorts. Of these, differential up-regulations of hsa-miR-6722-3p/-328-3p were validated in the plasma of MMD (Imposed threshold: absolute log2 expression fold change (logFC) > 0.26 for the twin cohort; absolute logFC > 0.26, p < 0.05, and q < 0.15 for the non-twin cohort). In MMD derived iPSECs, hsa-miR-6722-3p/-328-3p showed a trend of up-regulation with a 3.0- or higher expression fold change. Bioinformatics analysis revealed that 41 target genes of miR- 6722-3p/-328-3p were significantly down-regulated in MMD derived iPSECs and were involved in STAT3, IGF-1-, and PTEN-signaling, suggesting a potential microRNA- gene expression interaction between circulating plasma and endothelial cells. In conclusion, our MMD-discordant monozygotic twin-based study confirmed a novel circulating microRNA signature in MMD as a potential diagnostic biomarker minimally confounded by genetic heterogeneity. The novel circulating microRNA signature can contribute for the future functional microRNA analysis to find new diagnostic and therapeutic target of MMD.

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Determination of the serum miRNA expression profile in human moyamoya disease (MMD)

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