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已发表论文
miR-146a 中的单核苷酸的多态性对 COX-2 的蛋白表达和慢性阻塞性肺疾病吸烟者肺功能的影响
Authors Wang R, Li M, Zhou SJ, Zeng DX, Xu X, Xu R, Sun GY
Published Date March 2015 Volume 2015:10(1) Pages 463—473
DOI http://dx.doi.org/10.2147/COPD.S74345
Received 15 September 2014, Accepted 22 October 2014, Published 4 March 2015
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
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
