The Role Of CircRNA And CircRNA-miRNA-mRNA Network In The Pathogenesis Of Allergic Rhinitis

ObjectiveAllergic rhinitis（AR）is a common chronic,non-infectious,allergic inflammatory disease of the upper respiratory tract.As a completing endogenous RNA of mRNA,circRNA plays an important role in many diseases.The aim of this study was to synthetically analyze the expression and mechanism of circRNA in AR nasal mucosa by constructing a circRNA-miRNA-mRNA network.MethodsIn this study,the second-generation high-throughput sequencing technology was used to analyze the expression profiles of circRNA,miRNA and mRNA in nasal mucosa tissues of AR and control groups.The expression and characteristics of circRNA in the nasal mucosa were described,and the differential expression of large number of circRNA was selected.The standard of differential expression（DE）was that expression fold change>1.5 and p<0.05.The first 300 miRNA-circRNA interaction pairs with smaller p values were extracted basing on the overall differential circRNA enrichment results,and the network diagram of circRNA-miRNA target interaction was drawn.Using the same criteria,DEmiRNAs and DEmRNAs were selected.According to the bioinformatics analysis and the correlation between expression values of miRNA-target（circRNA or mRNA）,DEcircRNA-DEmiRNA-DEmRNA network based on ceRNA principle was constructed.The gene ontology（GO）functional annotations and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment were obtained using annotation and visualization database on coding Genes with ceRNA relationships in the network.Finally,Sanger sequencing and qRT-PCR were performed on hsa_circ₀008668,hsa_circ₀029853,circTRIQK and circRNA₀1002.ResultsA total of 30,936 circRNAs were predicted,including 12,376 known circRNAs and 18,560 newly discovered circRNAs.Among the circRNA types,sense genic exons were the most in the nasal mucosa.The number of exons in circRNA transcripts was mainly between 1-7,and the length was mostly between 200-400 bp and >2000 bp.There were 264 DEcircRNAs in AR nasal mucosa,of which 120 were up-regulated and 144 were down-regulated.There were 28 DEmiRNAs and 228 DEmRNAs.DEcircRNA-DEmiRNA-DEmRNA relationships in ceRNA network consist of 64 pairs,including 11 circRNAs,17 miRNAs and 29 mRNAs.The enrichment of GO and KEGG pathways showed that genes in the network were involved in Wnt signaling pathway,TNF,inflammatory response,PI3K-Akt signaling pathway,toll-like receptor（TLR）and other mechanisms related to AR.Sanger sequencing and qRT-PCR showed that hsa_circ₀008668 and circTRIQK were up-regulated,and hsa_circ₀029853 and circRNA₀1002 were down-regulated in AR,consistent with the sequencing results.ConclusioncircRNA was significantly correlated with AR,and the miRNA molecular sponge effect of circRNA may play an important role in the pathogenesis of AR.circRNA may provide a new direction for precision medicine of AR in the future.