miR-638 regulates gene expression networks associated with emphysematous lung destruction
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 phe...
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| Veröffentlicht in: | Genome medicine 2013-12, Vol.5 (12), p.114-114, Article 114 |
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| creator | 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 |
| description | 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.
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.
The expression levels of 63 microRNAs (P |
| doi_str_mv | 10.1186/gm519 |
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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.
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.
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.</description><identifier>ISSN: 1756-994X</identifier><identifier>EISSN: 1756-994X</identifier><identifier>DOI: 10.1186/gm519</identifier><identifier>PMID: 24380442</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Gene expression ; Genes ; Genetic aspects ; Genomes ; Genomics ; Lung diseases, Obstructive ; Messenger RNA ; MicroRNA</subject><ispartof>Genome medicine, 2013-12, Vol.5 (12), p.114-114, Article 114</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>Copyright © 2013 Christenson et al.; licensee BioMed Central Ltd. 2013 Christenson et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-34ef6b9207e32642e1477be681ddfe9291565c5c93b3edf5ce18c5ad8a0afa553</citedby><cites>FETCH-LOGICAL-c461t-34ef6b9207e32642e1477be681ddfe9291565c5c93b3edf5ce18c5ad8a0afa553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971345/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971345/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24380442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Christenson, Stephanie A</creatorcontrib><creatorcontrib>Brandsma, Corry-Anke</creatorcontrib><creatorcontrib>Campbell, Joshua D</creatorcontrib><creatorcontrib>Knight, Darryl A</creatorcontrib><creatorcontrib>Pechkovsky, Dmitri V</creatorcontrib><creatorcontrib>Hogg, James C</creatorcontrib><creatorcontrib>Timens, Wim</creatorcontrib><creatorcontrib>Postma, Dirkje S</creatorcontrib><creatorcontrib>Lenburg, Marc</creatorcontrib><creatorcontrib>Spira, Avrum</creatorcontrib><title>miR-638 regulates gene expression networks associated with emphysematous lung destruction</title><title>Genome medicine</title><addtitle>Genome Med</addtitle><description>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.
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.
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.
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.</description><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Lung diseases, Obstructive</subject><subject>Messenger RNA</subject><subject>MicroRNA</subject><issn>1756-994X</issn><issn>1756-994X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNptkl9rFDEUxYMottZ-BQmIxZdpJ5N_My9CKVoLBaEo6FPIZu7MRDPJmmSs_fbNum3ZBQkkIfmdQ87NReiY1KeEtOJsnDnpnqFDIrmouo59f76zP0CvUvpZ14I1TL5EBw2jbc1Yc4h-zPamErTFEcbF6QwJj-ABw991hJRs8NhDvg3xV8I6pWBsYXp8a_OEYV5PdwlmncOSsFv8iHtIOS4mF91r9GLQLsHxw3qEvn36-PXic3X95fLq4vy6MkyQXFEGg1h1TS2BNuV9QJiUKxAt6fsBuqYjXHDDTUdXFPqBGyCt4bpvda0HzTk9Qh-2vutlNUNvwOeonVpHO-t4p4K2av_G20mN4Y-inSSUbQzePxjE8HspAdRskwHntIcSTBHeCEnLxAr6douO2oGyfgjF0Wxwdc4pky0VXBbq9D9UGT3M1gQPgy3ne4KTHcEE2uUpBbdsypj2wXdb0MSQUoThKSap1aYN1L82KNyb3Zo8UY__Tu8BZO-tvg</recordid><startdate>20131231</startdate><enddate>20131231</enddate><creator>Christenson, Stephanie A</creator><creator>Brandsma, Corry-Anke</creator><creator>Campbell, Joshua D</creator><creator>Knight, Darryl A</creator><creator>Pechkovsky, Dmitri V</creator><creator>Hogg, James C</creator><creator>Timens, Wim</creator><creator>Postma, Dirkje S</creator><creator>Lenburg, Marc</creator><creator>Spira, Avrum</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131231</creationdate><title>miR-638 regulates gene expression networks associated with emphysematous lung destruction</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-34ef6b9207e32642e1477be681ddfe9291565c5c93b3edf5ce18c5ad8a0afa553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Lung diseases, Obstructive</topic><topic>Messenger RNA</topic><topic>MicroRNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Christenson, Stephanie A</creatorcontrib><creatorcontrib>Brandsma, Corry-Anke</creatorcontrib><creatorcontrib>Campbell, Joshua D</creatorcontrib><creatorcontrib>Knight, Darryl A</creatorcontrib><creatorcontrib>Pechkovsky, Dmitri V</creatorcontrib><creatorcontrib>Hogg, James C</creatorcontrib><creatorcontrib>Timens, Wim</creatorcontrib><creatorcontrib>Postma, Dirkje S</creatorcontrib><creatorcontrib>Lenburg, Marc</creatorcontrib><creatorcontrib>Spira, Avrum</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Christenson, Stephanie A</au><au>Brandsma, Corry-Anke</au><au>Campbell, Joshua D</au><au>Knight, Darryl A</au><au>Pechkovsky, Dmitri V</au><au>Hogg, James C</au><au>Timens, Wim</au><au>Postma, Dirkje S</au><au>Lenburg, Marc</au><au>Spira, Avrum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-638 regulates gene expression networks associated with emphysematous lung destruction</atitle><jtitle>Genome medicine</jtitle><addtitle>Genome Med</addtitle><date>2013-12-31</date><risdate>2013</risdate><volume>5</volume><issue>12</issue><spage>114</spage><epage>114</epage><pages>114-114</pages><artnum>114</artnum><issn>1756-994X</issn><eissn>1756-994X</eissn><abstract>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.
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.
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.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24380442</pmid><doi>10.1186/gm519</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central; Springer Nature OA/Free Journals; SpringerLink Journals - AutoHoldings |
| subjects | Gene expression Genes Genetic aspects Genomes Genomics Lung diseases, Obstructive Messenger RNA MicroRNA |
| title | miR-638 regulates gene expression networks associated with emphysematous lung destruction |
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