MicroRNAs in atrial fibrillation target genes in structural remodelling.
Atrial fibrillation
Fibrosis
MicroRNA
Structural remodelling
Transcriptome sequencing
Journal
Cell and tissue research
ISSN: 1432-0878
Titre abrégé: Cell Tissue Res
Pays: Germany
ID NLM: 0417625
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
01
03
2022
accepted:
07
08
2023
medline:
6
12
2023
pubmed:
14
10
2023
entrez:
13
10
2023
Statut:
ppublish
Résumé
We 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.
Identifiants
pubmed: 37833432
doi: 10.1007/s00441-023-03823-0
pii: 10.1007/s00441-023-03823-0
pmc: PMC10697892
doi:
Substances chimiques
MicroRNAs
0
RNA, Messenger
0
MIRN138 microRNA, human
0
MIRN206 microRNA, human
0
MIRN4306 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
497-514Subventions
Organisme : ZonMw
ID : 106.146.310
Pays : Netherlands
Informations de copyright
© 2023. The Author(s).
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