Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts
Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in...
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creator | Ong, Jennie van den Berg, Anke Faiz, Alen Boudewijn, Ilse M Timens, Wim Vermeulen, Cornelis J Oliver, Brian G Kok, Klaas Terpstra, Martijn M van den Berge, Maarten Brandsma, Corry-Anke Kluiver, Joost |
description | Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in primary lung fibroblasts. Small RNA sequencing was performed on lung fibroblasts from nine current and six ex-smokers with normal lung function. MiR-335-5p and miR-335-3p were significantly downregulated in lung fibroblasts from current compared to ex-smokers (false discovery rate (FDR) |
doi_str_mv | 10.3390/ijms20205176 |
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-value = 0.01). The results were validated in lung tissue from current and ex-smokers and in bronchial biopsies from non-diseased smokers and never-smokers (
-value <0.05). The methylation pattern of the miR-335 host gene, determined by methylation-specific qPCR, did not differ between current and ex-smokers. To obtain insights into the genes regulated by miR-335-5p in fibroblasts, we overlapped all proven miR-335-5p targets with our previously published miRNA targetome data in lung fibroblasts. This revealed
,
, and
as likely targets of miR-335-5p in lung fibroblasts. Our study indicates that miR-335-5p downregulation due to current smoking may affect its function in lung fibroblasts by targeting
,
and
.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20205176</identifier><identifier>PMID: 31635387</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Biomarkers ; Biopsy ; Cells, Cultured ; Chromosome 5 ; Cigarette smoking ; Cigarettes ; DNA Methylation ; Female ; Fibroblasts ; Fibroblasts - metabolism ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammation ; Kinases ; Lung - metabolism ; Lung - pathology ; Lung - physiopathology ; Lung diseases ; Lungs ; Male ; Methylation ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Respiratory function ; RNA Interference ; RNA, Messenger - genetics ; Smokers ; Smoking ; Smoking - adverse effects</subject><ispartof>International journal of molecular sciences, 2019-10, Vol.20 (20), p.5176</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-14315daf6dc4444b1a7ebc6dcc1c273685e90aff0f98d79c248fcb707aa42b763</citedby><cites>FETCH-LOGICAL-c412t-14315daf6dc4444b1a7ebc6dcc1c273685e90aff0f98d79c248fcb707aa42b763</cites><orcidid>0000-0002-7122-9262 ; 0000-0002-3280-1414 ; 0000-0002-8894-2638 ; 0000-0001-8655-3439 ; 0000-0002-4146-6363</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829537/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829537/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31635387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ong, Jennie</creatorcontrib><creatorcontrib>van den Berg, Anke</creatorcontrib><creatorcontrib>Faiz, Alen</creatorcontrib><creatorcontrib>Boudewijn, Ilse M</creatorcontrib><creatorcontrib>Timens, Wim</creatorcontrib><creatorcontrib>Vermeulen, Cornelis J</creatorcontrib><creatorcontrib>Oliver, Brian G</creatorcontrib><creatorcontrib>Kok, Klaas</creatorcontrib><creatorcontrib>Terpstra, Martijn M</creatorcontrib><creatorcontrib>van den Berge, Maarten</creatorcontrib><creatorcontrib>Brandsma, Corry-Anke</creatorcontrib><creatorcontrib>Kluiver, Joost</creatorcontrib><title>Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in primary lung fibroblasts. Small RNA sequencing was performed on lung fibroblasts from nine current and six ex-smokers with normal lung function. MiR-335-5p and miR-335-3p were significantly downregulated in lung fibroblasts from current compared to ex-smokers (false discovery rate (FDR) <0.05). Differential miR-335-5p expression was validated with RT-qPCR (
-value = 0.01). The results were validated in lung tissue from current and ex-smokers and in bronchial biopsies from non-diseased smokers and never-smokers (
-value <0.05). The methylation pattern of the miR-335 host gene, determined by methylation-specific qPCR, did not differ between current and ex-smokers. To obtain insights into the genes regulated by miR-335-5p in fibroblasts, we overlapped all proven miR-335-5p targets with our previously published miRNA targetome data in lung fibroblasts. This revealed
,
, and
as likely targets of miR-335-5p in lung fibroblasts. Our study indicates that miR-335-5p downregulation due to current smoking may affect its function in lung fibroblasts by targeting
,
and
.</description><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Cells, Cultured</subject><subject>Chromosome 5</subject><subject>Cigarette smoking</subject><subject>Cigarettes</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lung - physiopathology</subject><subject>Lung diseases</subject><subject>Lungs</subject><subject>Male</subject><subject>Methylation</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Respiratory function</subject><subject>RNA Interference</subject><subject>RNA, Messenger - genetics</subject><subject>Smokers</subject><subject>Smoking</subject><subject>Smoking - 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metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lung - physiopathology</topic><topic>Lung diseases</topic><topic>Lungs</topic><topic>Male</topic><topic>Methylation</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Respiratory function</topic><topic>RNA Interference</topic><topic>RNA, Messenger - genetics</topic><topic>Smokers</topic><topic>Smoking</topic><topic>Smoking - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ong, Jennie</creatorcontrib><creatorcontrib>van den Berg, Anke</creatorcontrib><creatorcontrib>Faiz, Alen</creatorcontrib><creatorcontrib>Boudewijn, Ilse M</creatorcontrib><creatorcontrib>Timens, Wim</creatorcontrib><creatorcontrib>Vermeulen, Cornelis J</creatorcontrib><creatorcontrib>Oliver, Brian G</creatorcontrib><creatorcontrib>Kok, Klaas</creatorcontrib><creatorcontrib>Terpstra, Martijn M</creatorcontrib><creatorcontrib>van den Berge, Maarten</creatorcontrib><creatorcontrib>Brandsma, Corry-Anke</creatorcontrib><creatorcontrib>Kluiver, Joost</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ong, Jennie</au><au>van den Berg, Anke</au><au>Faiz, Alen</au><au>Boudewijn, Ilse M</au><au>Timens, Wim</au><au>Vermeulen, Cornelis J</au><au>Oliver, Brian G</au><au>Kok, Klaas</au><au>Terpstra, Martijn M</au><au>van den Berge, Maarten</au><au>Brandsma, Corry-Anke</au><au>Kluiver, Joost</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-10-18</date><risdate>2019</risdate><volume>20</volume><issue>20</issue><spage>5176</spage><pages>5176-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in primary lung fibroblasts. Small RNA sequencing was performed on lung fibroblasts from nine current and six ex-smokers with normal lung function. MiR-335-5p and miR-335-3p were significantly downregulated in lung fibroblasts from current compared to ex-smokers (false discovery rate (FDR) <0.05). Differential miR-335-5p expression was validated with RT-qPCR (
-value = 0.01). The results were validated in lung tissue from current and ex-smokers and in bronchial biopsies from non-diseased smokers and never-smokers (
-value <0.05). The methylation pattern of the miR-335 host gene, determined by methylation-specific qPCR, did not differ between current and ex-smokers. To obtain insights into the genes regulated by miR-335-5p in fibroblasts, we overlapped all proven miR-335-5p targets with our previously published miRNA targetome data in lung fibroblasts. This revealed
,
, and
as likely targets of miR-335-5p in lung fibroblasts. Our study indicates that miR-335-5p downregulation due to current smoking may affect its function in lung fibroblasts by targeting
,
and
.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31635387</pmid><doi>10.3390/ijms20205176</doi><orcidid>https://orcid.org/0000-0002-7122-9262</orcidid><orcidid>https://orcid.org/0000-0002-3280-1414</orcidid><orcidid>https://orcid.org/0000-0002-8894-2638</orcidid><orcidid>https://orcid.org/0000-0001-8655-3439</orcidid><orcidid>https://orcid.org/0000-0002-4146-6363</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biomarkers Biopsy Cells, Cultured Chromosome 5 Cigarette smoking Cigarettes DNA Methylation Female Fibroblasts Fibroblasts - metabolism Gene expression Gene Expression Profiling Gene Expression Regulation Humans Inflammation Kinases Lung - metabolism Lung - pathology Lung - physiopathology Lung diseases Lungs Male Methylation MicroRNAs MicroRNAs - genetics miRNA Respiratory function RNA Interference RNA, Messenger - genetics Smokers Smoking Smoking - adverse effects |
title | Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts |
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