Current smoking is associated with decreased expression of mir-335-5p in parenchymal lung fibroblasts

Ong, J; Berg, AVD; Faiz, A; Boudewijn, IM; Timens, W; Vermeulen, CJ; Oliver, BG; Kok, K; Terpstra, MM; Berge, MVD; Brandsma, CA; Kluiver, J

Current smoking is associated with decreased expression of mir-335-5p in parenchymal lung fibroblasts

Ong, J Berg, AVD Faiz, A

Boudewijn, IM Timens, W Vermeulen, CJ

Oliver, BG

Kok, K

Terpstra, MM Berge, MVD Brandsma, CA Kluiver, J

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Publication Type:: Journal Article
Citation:: International Journal of Molecular Sciences, 2019, 20 (20)
Issue Date:: 2019-10-02

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Field	Value	Language
dc.contributor.author	Ong, J	en_US
dc.contributor.author	Berg, AVD	en_US
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Boudewijn, IM	en_US
dc.contributor.author	Timens, W	en_US
dc.contributor.author	Vermeulen, CJ https://orcid.org/0000-0002-3280-1414	en_US
dc.contributor.author	Oliver, BG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Kok, K https://orcid.org/0000-0001-8655-3439	en_US
dc.contributor.author	Terpstra, MM	en_US
dc.contributor.author	Berge, MVD	en_US
dc.contributor.author	Brandsma, CA	en_US
dc.contributor.author	Kluiver, J	en_US
dc.date.available	2019-10-16	en_US
dc.date.issued	2019-10-02	en_US
dc.identifier.citation	International Journal of Molecular Sciences, 2019, 20 (20)	en_US
dc.identifier.issn	1661-6596	en_US
dc.identifier.uri	http://hdl.handle.net/10453/136644
dc.description.abstract	© 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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 (p-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 (p-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 Rb1, CARF, and SGK3 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 Rb1, CARF and SGK3.	en_US
dc.relation.ispartof	International Journal of Molecular Sciences	en_US
dc.relation.isbasedon	10.3390/ijms20205176	en_US
dc.subject.classification	Chemical Physics	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Fibroblasts	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Smoking	en_US
dc.subject.mesh	DNA Methylation	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	RNA Interference	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Biomarkers	en_US
dc.subject.mesh	Smokers	en_US
dc.title	Current smoking is associated with decreased expression of mir-335-5p in parenchymal lung fibroblasts	en_US
dc.type	Journal Article
utslib.citation.volume	20	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0604 Genetics	en_US
utslib.for	0399 Other Chemical Sciences	en_US
utslib.for	0699 Other Biological Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	20	en_US
pubs.publication-status	Published	en_US
pubs.volume	20	en_US

Abstract:

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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 (p-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 (p-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 Rb1, CARF, and SGK3 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 Rb1, CARF and SGK3.

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http://hdl.handle.net/10453/136644