A Potential circRNA-miRNA-mRNA Regulatory Network in Asthmatic Airway Epithelial Cells Identified by Integrated Analysis of Microarray Datasets

Abstract

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.

A Novel Competing Endogenous RNA Network Associated With the Pathogenesis of Graves’ Ophthalmopathy

“…The MFs of these mRNAs, such as regulation of the immune response and inflammatory response, seem to be related to the pathogenesis of GO, but their exact relationship with GO needs further research. Moreover, hsa_circ_0000552 and hsa_circ_00009914 were dysregulated in asthmatic airway epithelial cells and patients’ hip joint synovial tissues who underwent revision operations for aseptic loosening after total hip arthroplasty ( Chen et al, 2021 ; Ni et al, 2021 ), which probably indicates that they have potential effects on these two diseases. Moreover, the constructed ceRNA network identified not only a series of RNAs with verified specific functions but also potentially unexplored RNAs, such as LINC01820:13, which showed high positive correlations with FPR2 and hsa-miR-27b-3p, and ENST00000499452, which is related to CXCL1 and hsa-miR-27a-3p.…”

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

“…As a result, the genes predicted by miRTarBase w/o other two databases were considered to be the target genes of DEM. To align DEM and DEGs, Cytoscape software (version 3.8.2) was utilized to illustrate the entire miRNA-mRNA regulation network ( Chen et al, 2021 ).…”

Recent miRNA Research in Asthma

“…The investigators reconstructed circular-RNA-miRNA-mRNA regulatory network using miRNA and mRNA expression data of bronchial brushing samples from asthma patients and healthy patients. Downstream analysis identified the top 10 epithelial RNAs: hsa_circ_0001585, hsa_circ_0078031, hsa_circ_0000552, miR-30a-3p, miR-30d-3p, KIT, CD69, ADRA2A, BPIFA1, and GGH, demonstrating the utility of the epithelial circRNA-miRNA-mRNA network in understanding the pathogenesis of asthma [70]. miR-21 dysregulation in the circulation and airways has been widely observed in allergic asthma and extensively investigated in humans and mice [71,72].…”