Differential Expression And Clinical Significance Of MicroRNAs In Chronic Obstructive Pulmonary Disease

Objectives:We established blood miRNAs expression profiling in chronic obstructive pulmonary disease(COPD)through chip database and the prominently dysregulated miRNAs were analysed by bioinformatics methods including target prediction,GO and Pathway analysis.On this basis,the candidate miRNAs expression were detected by qRT-PCR in PBMCs of COPD patients for the purpose of microarry data confirming.The clinical significance of these miRNAs were then explored.Methods:1 The blood miRNAs expression profiling in COPD were established through chip database.The dysregulated miRNAs and differentially expressed miRNAs in qPCR data from another independent cohort were intersected.The candidate miRNAs of COPD were selected.2 The target genes were analyzed by multiple databases like TargetScan?PicTar?miRDB and Tarbase.Took the intersection of three series of predicted target genes and merged with target genes which were verified by experiments.Those target genes were analyzed by bioinformatics methods including GO and Pathway analysis.3 The objects of study included healthy control subjects and COPD patients.The blood samples and clinic data of these individuals were collected.The expression of miRNAs(miR-23a?miR-25?miR-145?miR-224)in PBMCs were detected by qRT-PCR.The correlation analysis of miRNAs relative expression levels with GOLD grades and exacerbation frequency were conducted.4 The ROC analysis of miRNAs relative expression levels were performed.Results:1 There were 249 differentially expressing miRNAs between healthy control subjects and COPD patients by microarray data analysis,of which 98 miRNAs were up-regulated in COPD and 151 were down-regulated in COPD(P<0.05).Further qPCR indicated that the relative levels of miR-23a?miR-25?miR-145 and miR-224 were significantly down-regulated in COPD blood.2 A total of 3114 target genes of these 4 miRNAs were analyzed by bioinformatics methods.GO analysis showed that they were highly related to cell proliferation,differentiation,apoptosis,cell-cell signal,lipid metabolism and redox process.Pathway analysis showed those genes were closely associated with MAPK signal pathway?Wnt signal pathway?TGF-beta signal pathway?Notch signal pathway?T cell receptor signal pathway?B cell receptor signal pathway and so on.The dysregulated miRNAs may play important roles in the development and progression of COPD.3 A total of 30 healthy control subjecets and 50 COPD patients were recruited.The relative levels of miR-23a?miR-25?miR-145 and miR-224 were significantly lower in PBMCs of COPD patients.Besides,the levels in COPD patients were associated with GOLD stages.Further more,miR-23a and miR-145 were differentially expressed between frequent exacerbators and non-frequent exacerbators.4 The ROC analysis suggest that joint detection of miR-25?miR-145?miR-224 may predict COPD patients from healthy person.Conclusion:1 The dysregulated miRNAs(miR-23a?miR-25?miR-145?miR-224)may play an important role in the pathogenesis of COPD.2 The relative expression levels of miR-23a?miR-25?miR-145?miR-224 in PBMCs were significantly lower in COPD patients and were correlated with FEV1%pre.miR-23a and miR-145 were differentially expressed between frequent exacerbators and non-frequent exacerbators.3 Joint detection of miRNAs expression of miR-25?miR-145 and miR-224 may predict COPD patients from healthy person.