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Status |
Public on Nov 23, 2015 |
Title |
Persistence of Smoking-induced Dysregulation of Small Airway Epithelium miRNA Expression Despite Smoking Cessation |
Platform organism |
synthetic construct |
Sample organism |
Homo sapiens |
Experiment type |
Non-coding RNA profiling by array
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Summary |
Rationale: Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to never-smokers. Objectives: Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. Methods: SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 10 healthy never-smokers and 10 healthy smokers, before and after they quit for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. Results: There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy never-smokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway the top enriched pathway of the target genes of the persistent deregulated miRNAs. Conclusions: In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammation diseases or lung cancer, it is likely that persistent smoking-related changes in small airway epithelium miRNAs play a role in the subsequent development of these disorders.
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Overall design |
MicroRNA profiling identified 34 miRNAs up-regulated by cigarette smoking in human small airway epithelium. Even after quitting smoking for 3 months, 12 miRNAs didn’t return to normal level.
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Contributor(s) |
Wang G, Wang R, Strulovici-Barel Y, Salit J, Staudt MR, Ahmed J, Ann TE, Jenny Y, Charleen H, Ben-Gary H, Robert KJ, Jason MG, Sriram S, Sreekumar P, Holly H, Gerhard W, Hans B, Sudha V, Jay F, Chistopher SS, Crystal RG |
Citation(s) |
25886353 |
Submission date |
Dec 19, 2013 |
Last update date |
May 02, 2017 |
Contact name |
Yael Strulovici-Barel |
E-mail(s) |
yas2003@med.cornell.edu
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Organization name |
Weill Cornell Medical College
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Department |
Department of Genetic Medicine
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Lab |
Crystal
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Street address |
1300 York Avenue
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10021 |
Country |
USA |
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Platforms (1) |
GPL14613 |
[miRNA-2] Affymetrix Multispecies miRNA-2 Array |
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Samples (29)
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Relations |
BioProject |
PRJNA232262 |
Supplementary file |
Size |
Download |
File type/resource |
GSE53519_RAW.tar |
19.9 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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