AUTHOR=Wang Haixia , Zhang Zeyi , Ma Yu , Jia Yuanmin , Ma Bin , Gu Junlian , Chen Ou , Yue Shouwei 

TITLE=Construction of Severe Eosinophilic Asthma Related Competing Endogenous RNA Network by Weighted Gene Co-Expression Network Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.852536

DOI=10.3389/fphar.2022.852536

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Currently, disease control in patients with severe eosinophilic asthma is not optimistic. Competing endogenous RNA (ceRNA) networks have been found to play a key role in asthma in recent years. However, it is unclear whether ceRNA networks play an important part in severe eosinophilic asthma.</p><p><bold>Methods:</bold> Firstly, gene expression profiles related to severe eosinophilic asthma were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, the key modules were identified by the weighted gene co-expression network analysis (WGCNA). Thirdly, genes in modules highly associated with severe eosinophilic asthma were selected for further construction of the ceRNA network. Fourthly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on hub genes. Finally, the results of this study were validated on the GSE143303, GSE137268, and GSE147878 datasets.</p><p><bold>Results:</bold> 22 severe eosinophilic asthmatics and 13 healthy controls were extracted for WGCNA. We found that the genes in the black module (<italic>r</italic> = −0.75, <italic>p</italic> &lt; 0.05) and yellow module (<italic>r</italic> = 0.65, <italic>p</italic> &lt; 0.05) were highly associated with severe eosinophilic asthma. EP300 was discovered to serve the key connecting function in the ceRNA network. Surprisingly, lncRNAs seem to eliminate the role of EP300 in the black module and we discovered that CCT8 and miRNA-mRNA formed a circRNA-miRNA-mRNA network in the yellow module. We found that EP300 and FOXO3 in the black module were regulated by steroid hormones in the enrichment analysis, which were related to the medication used by the patient. Through validation of other datasets, we found that the hub genes in the yellow module were the key genes in the treatment of severe eosinophilic asthma. In particular, RPL17 and HNRNPK might specifically regulate severe eosinophilic asthma.</p><p><bold>Conclusion:</bold> RPL17 and HNRNPK might particularly regulate severe eosinophilic asthma. Our results could be useful to provide potential immunotherapy targets and prognostic markers for severe eosinophilic asthma.</p>