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

Background 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. Methods 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. Results 22 severe eosinophilic asthmatics and 13 healthy controls were extracted for WGCNA. We found that the genes in the black module (r = -0.75, P < 0.05) and yellow module (r = 0.65, P < 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. Conclusions 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.

Related Keywords

Kyoto ,Japan ,China ,Clemi ,Sichuan ,South Korea ,Shandong ,Jiangsu ,Han ,Cluego Bindea ,Azimzadeh Jamalkandi ,Expression Network Construction ,Natural Science Foundation Of Shandong Province ,Key Research ,Development Program Of Shandong Province ,Thomson ,Coexpression Network Analysis ,Human Asthmatic Airways ,Network Revealed Novel Long Rnas ,Rnpk Axis Promotes Primary Liver Cancer Development ,Development Of Asthma ,Protein Association Networks ,Network Construction ,Airway Inflammation ,Impairment Domain Of The Expert Panel ,Gibson ,Pathway Annotation Networks ,National Natural Science Foundation Of China ,Cerna Network ,Network Identifies Signature ,R Package For Weighted Correlation Network Analysis ,Adscs Attenuate Airway ,Gene Co Expression ,Gene Expression Omnibus ,Consensus Module ,External Clinical ,Gene Ontology ,Kyoto Encyclopedia ,Competing Endogenous ,Clinically Significant Module ,Gene Significance ,National Natural Science Foundation ,Natural Science Foundation ,Shandong Province ,Development Program ,Supplementary Material ,Cytoscape Plug In ,Decipher Functionally Grouped Gene Ontology ,Pathway Annotation ,Med Abstract ,Crossref Full Text ,Histone Acetylation ,Affect Airway Inflammation ,Emerging Functions ,Splicing Factor ,Silencing Protects ,Experimental Allergic ,Systematic Analysis ,Network Identifies ,Prognostic Biomarker ,Enhance Acute Lung ,Expression Omnibus ,Public Archive ,Gene Expression ,Inflammatory Diseases ,Epigenetic Promotion ,Consistently Very Poorly Controlled Asthma ,Impairment Domain ,Expert Panel Report ,Increases Risk ,Future Severe Asthma Exacerbations ,Natural History ,Treatment Regimens ,Critical Genes Associated ,Co Expression Modules ,Therapeutic Value ,Mediated Allergic ,Histone Deacetylases ,Human Asthmatic ,Sputum Eosinophils Predict Loss ,Redefined Confidence Scoring System ,Metabolomic Study ,Lung Function ,Weighted Correlation Network ,Physical Interaction ,Airway Inflammation Assessed ,Noninvasive Means ,Severe Asthma ,Asthma Related Competing Endogenous ,Revealed Novel Long Non Coding ,Potential New ,Glucocorticoid Receptor Target ,Own Expression Based ,Positive Autoregulatory ,Identify Potential Biomarkers ,Common Chronic Lung Inflammatory ,Promotes Primary Liver Cancer Development ,Hepatic Progenitor ,Proinflammatory Cytokines ,Are Increased ,Care Reduced ,Proteostasis Essential ,Trans Membrane Segment ,Ribosome Exit Tunnel Triggers ,Six Gene ,Endobronchial Biopsies ,Biopsies Identifies Novel Genes ,Pathways Linked ,Neutrophilic Inflammation ,Attenuate Airway Remodeling ,Enhancing Foxo ,Nucleic Acids ,Functional Protein Association ,Ige Therapy Inhibits Chemotaxis ,Circulating Fibrocytes ,Severe Allergic ,Emerging Roles ,Functional Polymorphism ,Increased Allele Specific Transcription ,Transcription Factor ,Distinctive Dendritic Cell Modulation ,Blood Biomarker ,Coexpression Network ,Transcriptome Characterization ,Short Distance Transport Stress ,Beef Cattle ,Severe Eosinophilic Asthma ,Ompeting Endogenous Rna ,O Expression Network Analysis ,Gcna Weighted Gene Co Expression Network Analyses ,Circrna ,