Identification of circRNA-miRNA-mRNA Regulatory Networks for Exploring Potential Therapeutic Drugs of Ischemic Stroke
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0310
- VernacularTitle:circRNA-miRNA-mRNA调控网络的挖掘以筛选缺血性脑卒中的潜在治疗药物
- Author:
Yumin WU
1
;
Zhongxing WANG
1
;
Yu YU
1
Author Information
1. Department of Anesthesiology， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
ischemic stroke;
circRNA;
mRNA;
competitive endogenous RNA;
connectivity map database
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(3):456-465
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo unearth novel circRNA-miRNA-mRNA network and potential drugs in ischemic stroke. MethodsData from the GEO database were utilized， focusing on three datasets （GSE115697， GSE51586， and GSE137482） that examine RNA expression levels in middle cerebral artery occlusion （MCAO） mouse models. Differentially expressed mRNA （DEmRNA）， DEcircRNA， and DEmiRNA were identified using the Limma package in R. A comprehensive strategy combining bioinformatics tools such as MiRWalk and StarBase was employed to identify circRNA-miRNA-mRNA networks associated with ischemic stroke. Hub sub-networks were screened and visualized using Cytoscape software. Functional analyses of the ceRNA networks were performed using Gene Ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomics （KEGG） pathway analysis， with pathways containing more than 10 enriched genes and an false discovery rate （FDR） ＜ 0.05 considered statistically significant. Lastly， the Connectivity Map （CMap） was applied to identify potential therapeutic drugs for ischemic stroke and the MCAO model was established in wild-type mice to verify the therapeutic effect. ResultsTotally， 1，249 DEmRNA， 294 DEmiRNA and 70 DEcircRNA were identified and it was found that 3 circRNA-miRNA-mRNA networks might be closely related to ischemic stroke. Based on these findings， Austricine， Metyrapone and Desoxypeganine were the most likely drugs that able to reverse the changes caused by stroke-related ceRNA networks. Metyrapone， taken as an example， was validated to improve neurological function damage on the first （P=0.001 4） and second （P=0.016 1） days post-surgery and reduce infarct volume （P=0.004 9）， thereby exerting a neuroprotective effect in ischemic stroke. ConclusionsOur study provides a novel insight into the pathogenesis and therapy of ischemic stroke from the perspective of circRNA-miRNA-mRNA regulatory network. The three drugs predicted in our research provide new clues for the treatment of ischemic stroke.
