Altered MicroRNA Expression in Intracranial Aneurysmal Tissues: Possible Role in TGF-β Signaling Pathway.
Aneurysmal subarachnoid haemorrhage
Intracranial aneurysm
Mitogen-activated protein kinases
Transforming growth factor-beta
microRNA
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
02
11
2020
accepted:
21
06
2021
pubmed:
30
6
2021
medline:
31
8
2022
entrez:
29
6
2021
Statut:
ppublish
Résumé
The molecular mechanisms behind the rupture of intracranial aneurysms remain obscure. MiRNAs are key regulators of a wide array of biological processes altering protein synthesis by binding to target mRNAs. However, variations in miRNA levels in ruptured aneurysmal wall have not been completely examined. We hypothesized that altered miRNA signature in aneurysmal tissues could potentially provide insight into aneurysm pathophysiology. Using a high-throughput miRNA microarray screening approach, we compared the miRNA expression pattern in aneurysm tissues obtained during surgery from patients with aneurysmal subarachnoid hemorrhage (aSAH) with control tissues (GEO accession number GSE161870). We found that the expression of 70 miRNAs was altered. Expressions of the top 10 miRNA were validated, by qRT-PCR and results were correlated with clinical characteristics of aSAH patients. The level of 10 miRNAs (miR-24-3p, miR-26b-5p, miR-27b-3p, miR-125b-5p, miR-143-3p, miR-145-5p, miR-193a-3p, miR-199a-5p, miR-365a-3p/365b-3p, and miR-497-5p) was significantly decreased in patients compared to controls. Expression of miR-125b-5p, miR-143-3p and miR-199a-5p was significantly decreased in patients with poor prognosis and vasospasm. The target genes of few miRNAs were enriched in Transforming growth factor-beta (TGF-β) and Mitogen-activated protein kinases (MAPK) pathways. We found significant negative correlation between the miRNA and mRNA expression (TGF-β1, TGF-β2, SMAD family member 2 (SMAD2), SMAD family member 4 (SMAD4), MAPK1 and MAPK3) in aneurysm tissues. We suggest that miR-26b, miR-199a, miR-497and miR-365, could target multiple genes in TGF-β and MAPK signaling cascades to influence inflammatory processes, extracellular matrix and vascular smooth muscle cell degradation and apoptosis, and ultimately cause vessel wall degradation and rupture.
Identifiants
pubmed: 34185228
doi: 10.1007/s10571-021-01121-3
pii: 10.1007/s10571-021-01121-3
doi:
Substances chimiques
MIRN145 microRNA, human
0
MIRN365 microRNA, human
0
MIRN497 microRNA, human
0
MicroRNAs
0
RNA, Messenger
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2393-2405Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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