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Association of Lung Tissue MicroRNA Expression with Quantitative Emphysema in COPD: An Exploratory Transcriptomic Analysis

Year: 2026

Type: article

Abstract: Background: MicroRNAs (miRNAs) may participate in biological pathways relevant to emphysema, but their associations with quantitative emphysema in human lung tissue remain uncertain. Methods: We analyzed lung tissue miRNA expression and clinical phenotypes from 117 patients with COPD/emphysema in GSE201121. After expression filtering, 839 miRNA loci were evaluated for association with percent emphysema (quantitative CT-derived percent low-attenuation area below − 950 HU) using linear regression adjusted for age and sex with HC3 heteroskedasticity-robust standard errors. Multiple testing was controlled using the Benjamini-Hochberg false discovery rate (BH-FDR). Significant loci were collapsed to unique mature miRNAs. Secondary analyses examined associations with FEV 1 % predicted, FEV 1 /FVC, and DLCO. Sensitivity analyses excluded influential observations, used log-transformed percent emphysema, and evaluated former smokers with adjustment for pack-years. Experimentally validated miRNA-target interactions were queried using multiMiR , followed by Gene Ontology Biological Process enrichment. Results: Fourteen miRNAs were associated with percent emphysema at BH-FDR < 0.05. Eight miRNAs showed positive associations with emphysema (miR-144-5p, miR-190a, miR-20b-5p, miR-451a, miR-3912, miR-15a-5p, miR-202-5p, and miR-4497), whereas six showed negative associations (miR-489, miR-181b-5p, miR-378a-5p, miR-3614-5p, miR-197-3p, and miR-877-3p). Associations with lung function were consistent with the emphysema findings across all 14 miRNAs. After phenotype-specific BH-FDR correction, 12 miRNAs were associated with FEV 1 % predicted, 12 with FEV 1 /FVC, and 8 with DLCO. All 14 associations retained their direction and significance across sensitivity analyses. Enrichment analyses of experimentally supported targets identified processes related to miRNA regulation, apoptosis, hypoxia/oxygen responses, cell-cycle regulation, and vasculature development. Conclusion: Lung-tissue expression of 14 mature miRNAs was associated with percent emphysema and lung function in COPD, while target-enrichment findings based on experimentally supported interaction databases were exploratory and require independent and functional validation. Keywords: microRNA, COPD, emphysema, lung function

Source: International Journal of COPD

DOI: 10.2147/copd.s653811

Authors: Taeyun Kim, Hyunji Choi, Chul-Ho Oak, Taehwa Kim, Tae Won Jang

Institutions: Kosin University Gospel Hospital, Kosin University

Language: English

Topic: Chronic Obstructive Pulmonary Disease (COPD) Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836