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

Abstract

Background The key differentially expressed autophagy-related genes(DE-ARGs) in childhood asthma were screened, and lncRNA-miRNA-mRNA networks were constructed to further understand the pathogenesis of asthma. Methods DE-ARGs were identified using the Gene Expression Database (GEO) and the Human Autophagy Database. These DE-ARGs were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene Set Enrichment Analysis, and protein-protein interaction network analysis followed by further verification of core gene expression. MiRNAs were inversely predicted using two databases (miRDB and ENCORI), while miRNA-lncRNA interactions were predicted using LncBase and ENCORI databases. After excluding lncRNAs present only in the nucleus and extracellular space, a competitive endogenous RNA (ceRNA) network was established and further analyzed. Finally, we validated mRNA expression levels in the ceRNA network by quantitative real-time PCR (qRT-PCR). Results 31 DE-ARGs were obtained, of which 29 were up-regulated and two were down-regulated. Autophagy, regulation of apoptotic signaling pathways, interferon-α/β signaling, interferon γ signaling, autophagy-animal, and apoptosis pathways were mainly enriched in asthma. Five hub genes (VEGFA, CFLAR, RELA, FAS, and ATF6) were further analyzed to verify the expression and diagnostic efficacy of these core genes using the GEO dataset. Finally, four hub genes (VEGFA, CFLAR, RELA, and FAS) were obtained. Through the combination of literature search, ceRNA network mechanism, and predicted miRNAs and lncRNAs analysis, a ceRNA network of four mRNAs (VEGFA, CFLAR, RELA, and FAS), three miRNAs (hsa-miR-320b, hsa-miR-22-3p, and hsa-miR-625-5p), and 35 lncRNAs was finally constructed. qRT-PCR showed that FAS was signifcantly upregulated. Conclusion Four DE-ARGs, especially FAS, may play a key role in asthma. The new ceRNA network may help to explore the mechanism of autophagy in asthma, which may be important for the development of new treatment options.