Dataset Information

Integrated Analysis of Immune-Related circRNA-miRNA-mRNA Regulatory Network in Ischemic Stroke.

ABSTRACT:

Background

Stroke is the leading cause of death and disability worldwide, with ischemic stroke (IS) being the most prevalent type. Circular RNAs (circRNAs) are involved in the pathological process of IS and are promising biomarkers for the diagnosis of IS. However, studies focusing on circRNAs acting as microRNAs (miRNAs) sponges in regulating mRNA expression are currently scarce.

Methods

In this study, expression profiles of circRNAs (GSE195442), miRNAs (GSE117064), and mRNAs (GSE58294) from the Gene Expression Omnibus (GEO) database were analyzed. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by R software. The target miRNAs and target genes were predicted by several bioinformatics methods. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEmRNAs. Subsequently, the protein-protein interaction (PPI) network and the competing endogenous RNA (ceRNA) regulatory network were visualized by Cytoscape software. Finally, we further constructed an immune-related circRNA-miRNA-mRNA regulatory sub-network in IS.

Results

A total of 35 DEcircRNAs, 141 DEmiRNAs, and 356 DEmRNAs were identified. By comprehensive analysis of bioinformatics methods, we constructed a circRNA-miRNA-mRNA regulatory network, including 15 DEcircRNAs, eight DEmiRNAs, and 39 DEmRNAs. FGF9 was identified as an immune-related hub gene. Immune cell analysis indicated a significantly higher level of neutrophils in IS, and the expression of FGF9 was significantly negatively correlated with the level of neutrophils. Eventually, miR-767-5p was predicted as the upstream molecules of FGF9, and circ_0127785 and circ_0075008 were predicted as the upstream circRNAs of miR-767-5p.

Conclusion

Our study provides novel insights into the molecular mechanisms governing the progression of IS from the perspective of immune-related ceRNA networks.

SUBMITTER: Cao S

PROVIDER: S-EPMC9240315 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Asthma is one of the most prevalent chronic respiratory diseases worldwide. Bronchial epithelial cells play a critical role in the pathogenesis of asthma. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges to regulate downstream gene expression. However, the role of epithelial circRNAs in asthma remains to be investigated. This study aims to explore the potential circRNA-miRNA-messenger RNA (mRNA) regulatory network in asthma by integrated analysis of publicly available microarray datasets. Methods: Five mRNA microarray datasets derived from bronchial brushing samples from asthma patients and control subjects were downloaded from the Gene Expression Omnibus (GEO) database. The robust rank aggregation (RRA) method was used to identify robust differentially expressed genes (DEGs) in bronchial epithelial cells between asthma patients and controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to annotate the functions of the DEGs. Protein-protein interaction (PPI) analysis was performed to identify hub genes. Three miRNA databases (Targetscan, miRDB, and miRWalk) were used to predict the miRNAs which potentially target the hub genes. A miRNA microarray dataset derived from bronchial brushings was used to validate the miRNA-mRNA relationships. Finally, a circRNA-miRNA-mRNA network was constructed via the ENCORI database. Results: A total of 127 robust DEGs in bronchial epithelial cells between steroid-naïve asthma patients (n = 272) and healthy controls (n = 165) were identified from five mRNA microarray datasets. Enrichment analyses showed that DEGs were mainly enriched in several biological processes related to asthma, including humoral immune response, salivary secretion, and IL-17 signaling pathway. Nineteen hub genes were identified and were used to construct a potential epithelial circRNA-miRNA-mRNA network. The top 10 competing endogenous RNAs were hsa_circ_0001585, hsa_circ_0078031, hsa_circ_0000552, hsa-miR-30a-3p, hsa-miR-30d-3p, KIT, CD69, ADRA2A, BPIFA1, and GGH. Conclusion: Our study reveals a potential role for epithelial circRNA-miRNA-mRNA network in the pathogenesis of asthma.