Bioinformatics analysis of ceRNA network of autophagy-related genes in pediatric asthma

Abstract

The molecular underpinnings of pediatric asthma present avenues for targeted therapies. A deeper exploration into the significance of differentially expressed autophagy-related genes (DE-ARGs) and their interactions with the long noncoding RNA (lncRNA)–microRNA (miRNA)–mRNA network may offer insights into the pathogenesis of pediatric asthma. DE-ARGs were retrieved from the Gene Expression Omnibus and the Human Autophagy Database. These DE-ARGs were subjected to comprehensive analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene Set Enrichment Analysis, and protein–protein interaction networks. The identified DE-ARGs were further verified for core gene expression. The miRDB and ENCORI databases were used for inverse miRNA predictions. Furthermore, miRNA–lncRNA interactions were predicted using LncBase and ENCORI platforms. Following the exclusion of lncRNAs exclusively localized in the nucleus and extracellular space, a competitive endogenous RNA (ceRNA) network was established and subsequently subjected to detailed analysis. The mRNA expression patterns in the ceRNA network were validated using quantitative real-time PCR. In total, 31 DE-ARGs were obtained, of which 29 were up-regulated and 2 were down-regulated. Notably, the autophagy, regulation of apoptotic signaling pathways, interferon-α/β signaling, interferon γ signaling, autophagy-animal, and apoptosis pathways were predominantly enriched in pediatric asthma. Five hub genes (VEGFA, CFLAR, RELA, FAS, and ATF6) were further analyzed using the Gene Expression Omnibus dataset to verify their expression patterns and diagnostic efficacy. Four hub genes (VEGFA, CFLAR, RELA, and FAS) were obtained. Finally, a ceRNA network of 4 mRNAs (VEGFA, CFLAR, RELA, and FAS), 3 miRNAs (hsa-miR-320b, hsa-miR-22-3p, and hsa-miR-625-5p), and 35 lncRNAs was constructed by integrating data from literature review and analyzing the predicted miRNAs and lncRNAs. Moreover, the quantitative real-time PCR data revealed a pronounced upregulation of Fas cell surface death receptor. The identification of 4 DE-ARGs, especially Fas cell surface death receptor, has shed light on their potential pivotal role in the pathogenesis of pediatric asthma. The established ceRNA network provides novel insights into the autophagy mechanism in asthma and suggests promising avenues for the development of potential therapeutic strategies.