Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts

Ong, J; Faiz, A; Timens, W; van den Berge, M; Terpstra, MM; Kok, K; van den Berg, A; Kluiver, J; Brandsma, CA

Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts

Ong, J Faiz, A

Timens, W van den Berge, M Terpstra, MM Kok, K van den Berg, A Kluiver, J Brandsma, CA

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Publication Type:: Journal Article
Citation:: Scientific Reports, 2019, 9 (1)
Issue Date:: 2019-12-01

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Field	Value	Language
dc.contributor.author	Ong, J	en_US
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Timens, W	en_US
dc.contributor.author	van den Berge, M	en_US
dc.contributor.author	Terpstra, MM	en_US
dc.contributor.author	Kok, K	en_US
dc.contributor.author	van den Berg, A	en_US
dc.contributor.author	Kluiver, J	en_US
dc.contributor.author	Brandsma, CA	en_US
dc.date.available	2019-11-14	en_US
dc.date.issued	2019-12-01	en_US
dc.identifier.citation	Scientific Reports, 2019, 9 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/137480
dc.description.abstract	© 2019, The Author(s). COPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-β-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.	en_US
dc.relation.ispartof	Scientific Reports	en_US
dc.relation.isbasedon	10.1038/s41598-019-54728-4	en_US
dc.title	Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	9	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	0601 Biochemistry and Cell Biology	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
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	9	en_US

Abstract:

© 2019, The Author(s). COPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-β-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.

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http://hdl.handle.net/10453/137480