title: Effect of a single nucleotide polymorphism in miR-146a on COX-2 protein expression and lung function in smokers with chronic obstructive pulmonary disease.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China ; Hefei Prevention and Treatment Center for Occupational Diseases, Hefei, People's Republic of China.
authors.forename: Sijing
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Daxiong
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Division of Pulmonary/Critical Care Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Gengyun
authors.initials: G
authors.lastname: Sun
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology; D014162:Transfection
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: COPD; COX-2; SNP; lung function; miR-146a