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Long non-coding RNA profile of the intracranial artery in the patients with Moyamoya disease

ABSTRACT: We collected microsamples of the middle cerebral artery (MCA) from MMD patients (n = 21) and control patients (n = 11). Using microarray experiments, the profile of lncRNAs expression in MCA were compared between groups and differentially expressed lncRNAs (fold change > 2, q < 0.05) were identified. In addition, the neighboring coding gene whose transcription can be regulated in cis by the identified differentially expressed lncRNAs were investigated, and applied to Gene Ontology analysis for predicting those biological functions. We detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 up-regulated and 2 down-regulated lncRNAs in the MCA from the MMD patients. As for the prediction of biological function, Gene Ontology analyses with possible coding genes whose transcription are regulated in cis by the identified differentially expressed lncRNAs suggested the involvement in antibacterial humoral response, T cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis. Quantitative polymerase chain reaction demonstrated a similar lncRNAs expression to the microarray experiments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189993 | GEO | 2022/07/03

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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Long non-coding RNA profile of the intracranial artery in the patients with Moyamoya disease

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