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MicroRNA (miRNA) Expression in Circulating Leukocytes and Bioinformatic Analysis of Patients with Moyamoya Disease (MMD)

ABSTRACT: To investigate the differential expression of miRNAs in circulating leukocytes of patients with MMD. The results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change > 2.0 and P < 0.05), of which 7 were up-regulated and 5 were down-regulated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178501 | GEO | 2022/06/23

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.

Project description:Objective: MicroRNAs (miRNAs) in exosomes had been implicated differentially expressed in patient with moyamoya disease (MMD), but the miRNAs expression in circulating leukocytes remains unclear. This study was investigated on the differential expression of miRNAs in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. Materials and methods: A total of 30 patients with MMD and 10 healthy adults were enrolled in a stroke center from October 2017 to December 2018. The gene microarray was used to detect the differential expression profiles of miRNA in leukocytes between MMD patients and controls, and the differentially expressed miRNAs were verified by the method of real-time PCR. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the key signaling pathways and possible pathogenesis of MMD. Results: The microarray results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change >2.0, p < 0.05 and FDR <0.05), of which 8 miRNAs were upregulated (miRNA-142-5p, miRNA-29b-3p, miRNA-424-5p, MiRNA-582-5p, miRNA-6807-5p, miRNA-142-3p, miRNA-340-5p, miRNA-4270), and 4 miRNAs were downregulated (miRNA-144-3p, miRNA-451a, miRNA-486-5p, miRNA-363-3p). The real-time PCR confirmed seven differentially expressed miRNAs (p < 0.05), of which 4 miRNAs (miRNA-29b-3p, miRNA-142-3p, miRNA-340-5p, miRNA-582-5p) were upregulated, and 3 miRNAs (miRNA-363-3p, miRNA-451a and miRNA-486-5p) were downregulated. Both GO and KEGG analysis suggested that the Wnt signaling pathway may be involved in the pathogenesis of MMD. In addition, miRNAs were also differentially expressed among patients with subtypes of MMD. Conclusion: This study indicated that miRNAs are differentially expressed in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. The Wnt signaling pathway is probably involved in the pathogenesis of MMD.

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MicroRNA (miRNA) Expression in Circulating Leukocytes and Bioinformatic Analysis of Patients with Moyamoya Disease (MMD)

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