| [OBJECTIVE]Chronic Obstructive pulmonary disease is an irreversible and progressive lung disease and currently ranked as the fourth leading cause of death worldwide.The current guidelines and therapeutic measures are only focused on the treatment of the disease and reducing the rate of deterioration.So novel studies on the molecular mechanism associated with COPD are of great significance for early screening,detection and management of COPD.In recent years circular RNAs have proven to be emerging diagnostic biomarkers and therapeutic targets for certain diseases.Our study aimed to investigate the differential expression of circular RNAs and mRNAs from peripheral blood mononuclear cells by using high throughput sequencing and functional enrichment analysis and further establishing their potential role as a diagnostic biomarker in chronic obstructive pulmonary disease.[METHODS]In this study,ten human blood samples were collected prospectively out of which five were COPD patients group and five were the healthy control group.Furthermore,circRNAs expression in these peripheral blood mononuclear cells(PBMCs)were analyzed by using high-throughput sequencing and bioinformatics methods including differential gene analysis,target gene prediction,GO function enrichment analysis,KEGG pathway enrichment analysis,protein interaction analysis,small molecule drug prediction etc.for establishing its diagnostic value in COPD.The analysis of differentially expressed RNAs(DE RNAs)was carried by the limma software package.Moreover,the regulatory relationship of circRNA-miRNA of humans were predicted using the miRanda network.After the identification of miRNA targeting circRNA and all miRNA targeting genes based on TargetScan and miRanda,the ceRNA network of circRNA-miRNA-mRNA was constructed..[REesults]1)Five participants in the COPD group and control group were men of similar age groups(50-80 years old),all of them had a smoking history and the smoking age was more than 30 years.FEV1/FVC of five participants in the control group was more than 70%;FEVl/FVC of five participants in the COPD group was less than 70%.2)According to the standard P<0.05 and log2foldchange>1,114 differentially expressed circRNAs(57 up-regulated,57 down-regulated)and 58 significantly differentially expressed mRNAs(21 up-regulated,37 down-regulated)were screened in COPD group3)GO function and KEGG pathway enrichment analysis of DEmRNAs in the sequencing results showed that,GO analysis is mainly concentrated in negative regulation of growth hormone receptor signaling pathway,interleukin-2 binding,RNA dependent ATPase activity,response to noradrenaline,positive regulation of endogenous deoxyribonuclease activity,positive regulation of interleukin-18 production,negative regulation of high-pressure gated calcium channel activity,positive regulation of interleukin-5 secretion,positive regulation of NLRP3 inflammatory corpuscle complex assembly.KEGG analysis was mainly enriched in PI3K-Akt signaling pathway,IL-17 signaling pathway,Toll-like receptor signaling pathway,Wnt signaling pathway,IgA-producing intestinal immune network.These pathways are potentially important for COPD.4)According to the analysis of DEmRNAs PPI in the sequencing results,the core genes are MYO16,MYL4,SCN4A,NRCAM,HMCN1,MYOM2 and IQSEC35)The prediction results of small and medium molecular drugs in CMAP showed that hycantone,ascorbic acid,puromycin,canavanine,and lincomycin might be potential drugs for COPD.6)There are 60 differentially expressed circRNAs(23 up-regulated,37 down-regulated),39 miRNAs(28 up-regulated,10 down-regulated),and 13 differentially expressed mRNAs(5 up-regulated,8 down-regulated)in the circRNA-miRNA-mRNA regulatory network.[CONCLUSION]The present study showed that circRNA and mRNA were differentially expressed in human PBMCs of COPD patients.The differentially expressed circRNA related ceRNA network was analyzed which showed that these circRNAs might be a prospective diagnostic biomarker and therapeutic targets for COPD patients. |
PDF Full Text Request