Circulating miR-1246 in the progression of Chronic Obstructive Pulmonary Disease (COPD) in patients from the BODE cohort.
Background: COPD is characterized by a persistent inflammatory response, especially against cigarette smoke. COPD patients may develop varying degrees of emphysematous destruction of the lungs. A pathophysiological role for miRNAs in COPD has been suggested in several studies. We examined changes in...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de La Laguna (ULL) |
| Repositorio: | RIULL. Repositorio Institucional de la Universidad de La Laguna |
| OAI Identifier: | oai:riull.ull.es:915/41306 |
| Acceso en línea: | http://riull.ull.es/xmlui/handle/915/41306 |
| Access Level: | acceso abierto |
| Palabra clave: | COPD progression miRNAs emphysema |
| Sumario: | Background: COPD is characterized by a persistent inflammatory response, especially against cigarette smoke. COPD patients may develop varying degrees of emphysematous destruction of the lungs. A pathophysiological role for miRNAs in COPD has been suggested in several studies. We examined changes in microRNAs expression profile during 10 years follow-up in relation to COPD progression. Methods: Clinical and lung function parameters were registered from every subject included in the study. miRNAs expression was determined in 14 serum samples from 7 patients in two moments (4 smokers with COPD (BODE cohort) and 3 smokers without COPD) by next generation sequencing (NGS) at baseline and after 10 years follow-up. A validation study was performed by qPCR in 20 patients with COPD (13 emphysemadiagnosed by CTscan) and 10 smoker controls at baseline and after 10 years follow-up. hsamiRNA-20a-5p and hsa-let-7d-5p were used as endogenous controls. Results: A total of 198 miRNAs (≥10TPM) were identified by NGS. Between these, hsamiR-1246 was found significantly downregulated in COPD patients after 10 years when compared to baseline (p<0.0001, FDR=0.05). Seventy-five percent of these patients had an emphysema diagnose. In the validation analysis, when analyzed longitudinally, hsa-miR -1246 was significantly downregulated in COPD patients with emphysema after 10 years (p= 0.019). However, no association was found between the expression of miR-1246 and any other lung function parameters (FEV1, PaO2, DLCO, IC/TLC) within the follow-up period. GO and KEGG enrichment analysis revealed miR-1246 to be associated with target genes in several pathways involved in COPD/emphysema development. Conclusion: Our findings suggest that hsa-miR-1246 may act as a biomarker of emphysema in COPD. Functional analysis is guaranteed to elucidate its role in COPD. |
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