MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sriram Sridhar
PROVIDER: E-GEOD-14224 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium.
Schembri Frank F Sridhar Sriram S Perdomo Catalina C Gustafson Adam M AM Zhang Xiaoling X Ergun Ayla A Lu Jining J Liu Gang G Zhang Xiaohui X Bowers Jessica J Vaziri Cyrus C Ott Kristen K Sensinger Kelly K Collins James J JJ Brody Jerome S JS Getts Robert R Lenburg Marc E ME Spira Avrum A
Proceedings of the National Academy of Sciences of the United States of America 20090123 7
We have shown that smoking impacts bronchial airway gene expression and that heterogeneity in this response associates with smoking-related disease risk. In this study, we sought to determine whether microRNAs (miRNAs) play a role in regulating the airway gene expression response to smoking. We examined whole-genome miRNA and mRNA expression in bronchial airway epithelium from current and never smokers (n = 20) and found 28 miRNAs to be differentially expressed (P < 0.05) with the majority being ...[more]
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2011-12-30 | E-GEOD-34764 | biostudies-arrayexpress
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2008-11-07 | E-GEOD-5056 | biostudies-arrayexpress
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2012-12-05 | E-GEOD-34466 | biostudies-arrayexpress
Project description:Rationale: Genome-wide association studies (GWAS) and candidate gene studies have identified a number of loci linked to susceptibility of chronic obstructive pulmonary disease (COPD), a smoking-related disorder that originates in the airway epithelium. Objectives: Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome linked, in part, to known GWAS/candidate gene loci. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n=10) and smokers (n=7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS and candidate gene studies to confer risk for COPD. Measurements and Main Results: Smoker BC have 676 known genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10-4 compared to chance), including TGFB1, LTBP4, EGLN2 and NFKBIB, genes associated with risk for COPD. Conclusions: These observations provide the first direct link of known genetic risks for smoking-related lung disease with the specific population of lung cells that undergoes the earliest changes associated with smoking. The human airway basal cell transcriptome of 7 smokers versus 10 nonsmokers was compared using massive parallel RNA sequencing (Illumina HiSeq 2000).
2014-05-08 | E-GEOD-47718 | biostudies-arrayexpress
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