Bioinformatics-based identification of potential microRNA biomarkers in frequent and non-frequent exacerbators of COPD

Abstract

ObjectivesMicroRNAs (miRNAs) play essential roles in the development of COPD. In this study, we aimed to identify and validate potential miRNA biomarkers in frequent and non-frequent exacerbators of COPD patients using bioinformatic analysis.Materials and methodsThe candidate miRNA biomarkers in COPD were screened from Gene Expression Omnibus (GEO) dataset and identified using GEO2R online tool. Then, we performed bioinformatic analyses including target prediction, gene ontology (GO), pathway enrichment analysis and construction of protein–protein interaction (PPI) network. Furthermore, the expression of the identified miRNAs in peripheral blood monocular cells (PBMCs) of COPD patients was validated using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsMiR-23a, miR-25, miR-145 and miR-224 were identified to be significantly downregulated in COPD patients compared with healthy controls. GO analysis showed the four miRNAs involved in apoptotic, cell differentiation, cell proliferation and innate immune response. Pathway analysis showed that the targets of these miRNAs were associated with p53, TGF-β, Wnt, VEGF and MAPK signal pathway. In healthy controls, the miR-25 and miR-224 levels were significantly decreased in smokers compared with nonsmokers (P<0.001 and P<0.05, respectively). In COPD patients, the levels of miR-23a, miR-25, miR-145 and miR-224 were associated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. Notably, miR-23a and miR-145 were significantly elevated in non-frequent exacerbators compared with frequent exacerbators (P<0.05), and miR-23a showed higher area under the receiver–operator characteristic curve (AUROC) than miR-145 (0.707 vs 0.665, P<0.05).ConclusionMiR-23a, miR-25, miR-145 and miR-224 were associated with the development of COPD, and miR-23a might be a potential biomarker for discriminating the frequent exacerbators from non-frequent exacerbators.

Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease

“…Notch regulates heart and vascular functions during development and is involved in the repair of the damaged and/or stressed myocardium [29,78,79]. Dysregulation of the Notch pathway has been linked to atherosclerosis [80,81] and to COPD [82]. In COPD patients, reduced levels of NOTCH1 and HES1 have been shown in the endothelium [33] and in the airways epithelium [32].…”

miR‑106b‑5p modulates acute pulmonary embolism via NOR1 in pulmonary artery smooth muscle cells

“…Bioinfor matics analysis using TargetScan v7.2 (http://www.targetscan.org/vert_72/), PicTar (http://www.pictar.org/), and miRanda (http://www. microrna.org/microrna/home.do) predicted that NOR-1 was a potential target gene of miR-106b-5p (29,30). Plasmids containing a portion of wide type (WT) or mutated (Mut) 3-UTR of the NOR1 gene were synthesized by Guangzhou RiboBio co., Ltd. A total of 4x10 4 PASMcs/well were plated and co-transfected with 200 ng luciferase vector (Promega corporation) and 100 nM agomiR-106b-5p or agomiR-Nc using Lipofectamine ® 3000 reagent (Invitrogen; Thermo Fisher Scientific, Inc.).…”

Clinical differences between eosinophilic and non-eosinophilic acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a multicenter cross-sectional study

“…Although amount of potential biomarkers [7], from in ammatory mediators/proteins [8] to miRNAs [9,10], DNA methylation CpG sites [11,12], single nucleotide polymorphisms (SNPs) [13,14], and metabolites [15,16], were found, blood eosinophil (EOS) is considered to be a stable, available and acceptable marker in clinical practice [17,18]. Classically, COPD is considered as a Th1 dependent chronic airway in ammation.…”