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Circulating miR-1246 in the Progression of Chronic Obstructive Pulmonary Disease (COPD) in Patients from the BODE Cohort.

Abstract：

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 emphysema-diagnosed by CTscan) and 10 smoker controls at baseline and after 10 years follow-up. hsa-miRNA-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, hsa-miR-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.

journal_name

Int J Chron Obstruct Pulmon Dis

journal_title

International journal of chronic obstructive pulmonary disease

authors

Cazorla-Rivero S,Mura-Escorche G,Gonzalvo-Hernández F,Mayato D,Córdoba-Lanús E,Casanova C

doi

10.2147/COPD.S271864

subject

Has Abstract

pub_date

2020-10-29 00:00:00

pages

2727-2737

eissn

1176-9106

issn

1178-2005

pii

271864

journal_volume

pub_type

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Circulating miR-1246 in the Progression of Chronic Obstructive Pulmonary Disease (COPD) in Patients from the BODE Cohort.