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miR-638 regulates gene expression networks associated with emphysematous lung destruction

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 e...

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Autores principales: Christenson, Stephanie A, Brandsma, Corry-Anke, Campbell, Joshua D, Knight, Darryl A, Pechkovsky, Dmitri V, Hogg, James C, Timens, Wim, Postma, Dirkje S, Lenburg, Marc, Spira, Avrum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971345/
https://www.ncbi.nlm.nih.gov/pubmed/24380442
http://dx.doi.org/10.1186/gm519
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author Christenson, Stephanie A
Brandsma, Corry-Anke
Campbell, Joshua D
Knight, Darryl A
Pechkovsky, Dmitri V
Hogg, James C
Timens, Wim
Postma, Dirkje S
Lenburg, Marc
Spira, Avrum
author_facet Christenson, Stephanie A
Brandsma, Corry-Anke
Campbell, Joshua D
Knight, Darryl A
Pechkovsky, Dmitri V
Hogg, James C
Timens, Wim
Postma, Dirkje S
Lenburg, Marc
Spira, Avrum
author_sort Christenson, Stephanie A
collection PubMed
description 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 genome-wide microRNA expression is altered with regional emphysema severity and how these microRNAs regulate disease-associated gene expression networks. METHODS: We profiled microRNAs in different regions of the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified by mean linear intercept. Whole genome microRNA and gene expression data were integrated in the same samples to build co-expression networks. Candidate microRNAs were perturbed in human lung fibroblasts in order to validate these networks. RESULTS: The expression levels of 63 microRNAs (P < 0.05) were altered with regional emphysema. A subset, including miR-638, miR-30c, and miR-181d, had expression levels that were associated with those of their predicted mRNA targets. Genes correlated with these microRNAs were enriched in pathways associated with emphysema pathophysiology (for example, oxidative stress and accelerated aging). Inhibition of miR-638 expression in lung fibroblasts led to modulation of these same emphysema-related pathways. Gene targets of miR-638 in these pathways were amongst those negatively correlated with miR-638 expression in emphysema. 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 pathways related to the oxidative stress response and aging in emphysematous lung tissue and lung fibroblasts.
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spelling pubmed-39713452014-04-10 miR-638 regulates gene expression networks associated with emphysematous lung destruction Christenson, Stephanie A Brandsma, Corry-Anke Campbell, Joshua D Knight, Darryl A Pechkovsky, Dmitri V Hogg, James C Timens, Wim Postma, Dirkje S Lenburg, Marc Spira, Avrum Genome Med Research 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 genome-wide microRNA expression is altered with regional emphysema severity and how these microRNAs regulate disease-associated gene expression networks. METHODS: We profiled microRNAs in different regions of the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified by mean linear intercept. Whole genome microRNA and gene expression data were integrated in the same samples to build co-expression networks. Candidate microRNAs were perturbed in human lung fibroblasts in order to validate these networks. RESULTS: The expression levels of 63 microRNAs (P < 0.05) were altered with regional emphysema. A subset, including miR-638, miR-30c, and miR-181d, had expression levels that were associated with those of their predicted mRNA targets. Genes correlated with these microRNAs were enriched in pathways associated with emphysema pathophysiology (for example, oxidative stress and accelerated aging). Inhibition of miR-638 expression in lung fibroblasts led to modulation of these same emphysema-related pathways. Gene targets of miR-638 in these pathways were amongst those negatively correlated with miR-638 expression in emphysema. 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 pathways related to the oxidative stress response and aging in emphysematous lung tissue and lung fibroblasts. BioMed Central 2013-12-31 /pmc/articles/PMC3971345/ /pubmed/24380442 http://dx.doi.org/10.1186/gm519 Text en Copyright © 2013 Christenson et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Christenson, Stephanie A
Brandsma, Corry-Anke
Campbell, Joshua D
Knight, Darryl A
Pechkovsky, Dmitri V
Hogg, James C
Timens, Wim
Postma, Dirkje S
Lenburg, Marc
Spira, Avrum
miR-638 regulates gene expression networks associated with emphysematous lung destruction
title miR-638 regulates gene expression networks associated with emphysematous lung destruction
title_full miR-638 regulates gene expression networks associated with emphysematous lung destruction
title_fullStr miR-638 regulates gene expression networks associated with emphysematous lung destruction
title_full_unstemmed miR-638 regulates gene expression networks associated with emphysematous lung destruction
title_short miR-638 regulates gene expression networks associated with emphysematous lung destruction
title_sort mir-638 regulates gene expression networks associated with emphysematous lung destruction
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971345/
https://www.ncbi.nlm.nih.gov/pubmed/24380442
http://dx.doi.org/10.1186/gm519
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