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| Status |
Public on Dec 31, 2013 |
| Title |
microRNA expression associated with emphysematous lung destruction |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by varying degrees of emphysematous lung destruction and small airway disease, each with distinct effects on clinical outcomes. There is little known about how microRNAs contribute specifically to the emphysema phenotype. We examined how microRNA expression is altered with regional emphysema severity within the lung and how these microRNAs regulate disease-associated gene-expression networks. Results: We profiled microRNAs in different regions in the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions x 8 lungs = 64 samples). 63 microRNAs (p<0.05) were altered with regional emphysema severity as quantified by mean linear intercept (Lm). MicroRNA and gene expression data were then integrated in the same samples. A subset of microRNAs, including miR-638, miR-30c, and miR-181d, correlated with many of their predicted gene targets, suggesting a role in regulating the gene networks that underlie emphysematous lung destruction. Modulating miR-638 expression in primary human lung fibroblasts recapitulated the alterations in its targeted gene-expression network associated with emphysema progression. Pathway analysis revealed that genes involved in oxidative stress and accelerated aging were affected by miR-638 knock-down in fibroblasts. Many miR-638 gene targets in these pathways were amongst those negatively correlated with miR-638 expression in emphysematous lung tissue. Conclusions: Our findings demonstrate that microRNAs are altered with regional emphysema severity and modulate disease-associated gene expression networks. Furthermore, miR-638 may regulate gene expression associated with the oxidative stress response and aging in emphysematous lung tissue and fibroblasts.
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| Overall design |
Paired samples were obtained from 8 regions at regular intervals between the apex and base of each explanted lung from six patients with severe COPD and two donors. The degree of emphysematous destruction was quantified in one sample from each region by mean linear intercept (Lm), while microRNA expression was profiled in the adjacent sample from the same region using the NCode Version 3 microRNA microarrays (Invitrogen, Carlsbad, CA). After quality control 60 samples were used for the analysis.
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| Contributor(s) |
Christenson SA, Brandsma C, Campbell JD, Knight DA, Pechkovsky DV, Hogg JC, Timens W, Postma DS, Lenburg M, Spira A |
| Citation(s) |
24380442 |
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| Submission date |
Aug 14, 2013 |
| Last update date |
Feb 20, 2014 |
| Contact name |
Stephanie A Christenson |
| Organization name |
University of California, San Francisco
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| Department |
Pulmonary and Critical Care
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| Street address |
513 PARNASSUS AVENUE, HSE1305
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| City |
San Francisco |
| State/province |
California |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL15892 |
NCode Human miRNA microarray V3 |
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| Samples (57)
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| Relations |
| BioProject |
PRJNA215238 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49881_RAW.tar |
25.0 Mb |
(http)(custom) |
TAR (of CSV, XLS) |
| Processed data included within Sample table |
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