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Effect of a single nucleotide polymorphism in miR-146a on COX-2 protein expression and lung function in smokers with chronic obstructive pulmonary disease

Authors Wang R, Li M, Zhou SJ, Zeng DX, Xu X, Xu R, Sun GY

Received 15 September 2014

Accepted for publication 22 October 2014

Published 4 March 2015 Volume 2015:10(1) Pages 463—473

DOI https://doi.org/10.2147/COPD.S74345

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Richard Russell

Ran Wang,1,* Min Li,2,* Sijing Zhou,1,3 Daxiong Zeng,4 Xuan Xu,5 Rui Xu,1 Gengyun Sun1

1Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Hefei Prevention and Treatment Center for Occupational Diseases, Hefei, People’s Republic of China; 4Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Division of Pulmonary/Critical Care Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA

*These authors contributed equally to this work


Objective: To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population.
Methods and results: One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited. The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment. We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group. We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot. Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population.
Conclusion: In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production.

Keywords: SNP, miR-146a, COX-2, COPD, lung function

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