MicroRNAs in atrial fibrillation target genes in structural remodelling
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Published:2023-10-14
Issue:3
Volume:394
Page:497-514
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ISSN:0302-766X
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Container-title:Cell and Tissue Research
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language:en
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Short-container-title:Cell Tissue Res
Author:
van den Berg Nicoline W. E.ORCID, Kawasaki Makiri, Nariswari Fransisca A., Fabrizi Benedetta, Neefs Jolien, van der Made Ingeborg, Wesselink Robin, van Boven Wim Jan P., Driessen Antoine H. G., Jongejan Aldo, de Groot Joris R.
Abstract
AbstractWe aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA–mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Histology,Pathology and Forensic Medicine
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