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Circular RNA Profiling of Neutrophil Transcriptome Provides Insights into Asymptomatic Moyamoya Disease

ABSTRACT: Microarray based circRNAs profiling was determined between neutrophil samples from patients with asymptomatic MMD and healthy subjects. The microarray results were followingly confirmed by quantitative reverse-transcription PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses (KEGG) were adopted for annotation and predicting the functions of differentially expressed circRNAs. Results From this comparative circRNA microarray analysis of neutrophil samples from patients with asymptomatic MMD and healthy subjects, 123 circRNAs were identified differentially expressed between the two groups. Of these, 54 were upregulated and 69 were downregulated compared to controls (fold change > 2.0 and P < 0.05).

ORGANISM(S): Homo sapiens

PROVIDER: GSE130227 | GEO | 2020/05/01

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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Circular RNA Profiling of Neutrophil Transcriptome Provides Insights into Asymptomatic Moyamoya Disease

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