Unveiling circRNA-mediated ceRNA networks in ischemic stroke by integrative analysis of multi-source gene expression profiling

Abstract

Background: Circular RNAs (circRNAs) are emerging as potential therapeutic targets for ischemic stroke (IS) due to their regulatory roles in inflammation and apoptosis. This study aimed to develop a comprehensive and robust IS-specific competing endogenous RNA (ceRNA) network to facilitate the identification of novel diagnostic and therapeutic targets. Methods: We integrated expression data from 15 IS studies using the Rank-In algorithm to minimize batch effects. Differentially expressed circRNAs, miRNAs, and mRNAs were identified by comparing IS and control samples. Functional enrichment analysis of differentially expressed circRNA host genes revealed significantly enriched pathways and Gene Ontology (GO) terms relevant to IS pathogenesis. We further predicted miRNA-circRNA and mRNA-miRNA interactions, enabling the construction of a comprehensive ceRNA network to identify circRNA-related genes with diagnostic potential for IS. Results: Integrated analysis revealed 199 differentially expressed circRNAs, 103 miRNAs, and 1736 mRNAs in IS patients. Functional enrichment analysis implicated these molecules in relevant pathways like the neurotrophin signaling pathway and p53 signaling pathway. The constructed circRNA-miRNA-mRNA regulatory network provided insights into potential mechanisms underlying IS. Three circRNA-related genes (RGS2, CDK5R1, and NSF) displayed promising diagnostic potential for IS when combined. Conclusions: We successfully constructed a robust and informative IS-specific ceRNA network by integrating data from diverse sources. This network identified differentially expressed RNAs and revealed enriched pathways potentially involved in IS pathogenesis. Notably, our analysis identified CDK5R1, RGS2, and NSF as potential diagnostic biomarkers for IS. This study sheds light on a circRNA-mediated regulatory network with potential diagnostic and therapeutic implications for ischemic stroke.