Peripheral Blood Mononuclear Cell Gene Expression in Chronic Obstructive Pulmonary Disease: miRNA and mRNA Regulation

Abstract

Introduction The mechanisms underlying chronic obstructive pulmonary disease (COPD) remain unclear. Genetic and genomic changes may play a significant role in the pathogenesis of COPD. Identification of differentially expressed genes and miRNAs and their regulatory mechanisms at the whole-genome level will provide a comprehensive understanding of the development of COPD. Methods Peripheral blood mononuclear cells (PBMCs) from 12 patients with COPD and 12 normal controls were examined at the miRNA and mRNA expression levels using Affymetrix GeneChip. Microarray data were analyzed with Affymetrix Transcriptome Analysis Console 2.0 and GeneSpring software. Gene interaction pathways of the differentially expressed genes and miRNA-mRNA regulation were analyzed using the Ingenuity Pathway Analysis software. Four differentially expressed genes and one miRNA were further confirmed using RT-qPCR. Results One hundred and thirty-three upregulated and 973 downregulated genes were identified in PBMCs of patients with COPD. Pathway analysis on the differentially expressed genes in COPD revealed significant enrichment in IL-8 signaling and iCOS-iCOSL signaling in T helper cells. Seventy-seven upregulated miRNAs and 43 downregulated miRNAs were differentially expressed between PBMCs from patients with COPD and normal controls. Among these 120 differentially expressed miRNAs, 42 miRNAs targeting 28 upregulated genes and 69 miRNAs targeting 498 downregulated genes were identified. The expression of CXCR1, HBEGF, TREM-1, and hsa-miR-148a-3p was more elevated in patients with COPD than in normal controls, whereas NFAT5 was decreased. Conclusion miRNAs and mRNAs are differentially expressed in PBMCs of patients with COPD, compared with normal controls. miRNAs regulate the expression of mRNAs, and thus play a role in the pathogenesis of COPD. Investigating these relationships may provide further insight into the mechanisms of COPD.

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

“…Next, we focused on the downstream mechanism of MEG3 in COPD. Prior researchers pointed out the elevated TREM-1 expression in COPD patients versus the normal ( 31 ), which was consistent with our results that TREM-1 was upregulated in CES-derived exosomes-treated macrophages and COPD mouse lung tissues, which could be reduced by MEG3 inhibition. Further experiments confirmed that overexpressed TREM-1 reversed the mitigative effects of MEG3 inhibition on pyroptosis and M1 macrophage polarization, reflected by increased CD86 + cells and iNOS, TNF-α, IL-1β, NLRP3, ASC, cleaved-caspase-1, GSDMD, and GSDMD-N levels.…”

Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential

“…However, miR-15b-5p appeared to be most consistently downregulated [174,179]. Wang et al reported that, from 148 significantly identified miRNAs in the blood of COPD patients, 104 miRNAs were upregulated, and 44 miRNAs were downregulated [180]. Asthma and COPD overlap syndrome often reveals upregulated miRNA-338 in the sputum, while the expression of some other miRNAs is lowered (miR-148a-3p, miR-15b-5p, miR-223-3p, and miR-23a-3p) [174].…”

Mechanisms of Lung Damage and Development of COPD Due to Household Biomass-Smoke Exposure: Inflammation, Oxidative Stress, MicroRNAs, and Gene Polymorphisms

“…Several studies examining changes in the microRNA profiles of bronchial biopsies, lung tissue, airway cells, sputum, and peripheral blood in COPD patients have linked these changes to disease status, diagnosis, survival, pathogenesis, and response to corticosteroid treatment [152][153][154][155][156][157]. Furthermore, miRNA and mRNA expression studies on COPD patients have revealed miRNA-mRNA network interactions associated with potential pathogenesis mechanisms [153,158]. Therefore, increasing evidence suggests that miRNAs may play a crucial role in the pathogenesis and development of COPD.…”