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Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line.


ABSTRACT: BACKGROUND:Moyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Recently, differences in epigenetic regulations have been investigated by a case-control study in MMD. Here, we employed a disease discordant monozygotic twin-based study design to unmask potential confounders. METHODS: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. RESULTS: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 upregulations of hsa-miR-6722-3p/-?328-3p were validated in the plasma of MMD (absolute log2 expression fold change (logFC)?>?0.26 for the twin cohort; absolute logFC >?0.26, p?

SUBMITTER: Uchino H 

PROVIDER: S-EPMC6114494 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line.

Uchino Haruto H   Ito Masaki M   Kazumata Ken K   Hama Yuka Y   Hamauchi Shuji S   Terasaka Shunsuke S   Sasaki Hidenao H   Houkin Kiyohiro K  

BMC medical genomics 20180829 1


<h4>Background</h4>Moyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Recently, differences in epigenetic regulations have been investigated by a case-control study in MMD. Here, we employed a disease discordant monozygotic twin-based study design to unmask potential confounders.<h4>Methods</h4>Circulating genome-wide microRNA (miRNome) profili  ...[more]

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