Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer

The pulmonary endothelium is dysfunctional in chronic obstructive pulmonary disease (COPD), a known risk factor for lung cancer. The pulmonary endothelium is altered in emphysema, which is disproportionately affected by cancers. Gene and microRNA expression differs between COPD and non-COPD lung. We...

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Main Authors: Clara E. Green, Joseph Clarke, Roy Bicknell, Alice M. Turner
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/7/830
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author Clara E. Green
Joseph Clarke
Roy Bicknell
Alice M. Turner
author_facet Clara E. Green
Joseph Clarke
Roy Bicknell
Alice M. Turner
author_sort Clara E. Green
collection DOAJ
description The pulmonary endothelium is dysfunctional in chronic obstructive pulmonary disease (COPD), a known risk factor for lung cancer. The pulmonary endothelium is altered in emphysema, which is disproportionately affected by cancers. Gene and microRNA expression differs between COPD and non-COPD lung. We hypothesised that the alteration in microRNA expression in the pulmonary endothelium contributes to its dysfunction. A total of 28 patients undergoing pulmonary resection were recruited and endothelial cells were isolated from healthy lung and tumour. MicroRNA expression was compared between COPD and non-COPD patients. Positive findings were confirmed by quantitative polymerase chain reaction (qPCR). Assays assessing angiogenesis and cellular migration were conducted in Human Umbilical Vein Endothelial Cells (<i>n</i> = 3–4) transfected with microRNA mimics and compared to cells transfected with negative control RNA. Expression of miR-181b-3p, miR-429 and miR-23c (all <i>p</i> < 0.05) was increased in COPD. Over-expression of miR-181b-3p was associated with reduced endothelial sprouting (<i>p</i> < 0.05). miR-429 was overexpressed in lung cancer as well and exhibited a reduction in tubular formation. MicroRNA-driven changes in the pulmonary endothelium thus represent a novel mechanism driving emphysema. These processes warrant further study to determine if they may be therapeutic targets in COPD and lung cancer.
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spelling doaj.art-44b35a3130e84602ac505c05f4c0a91e2023-11-22T03:17:43ZengMDPI AGBiomedicines2227-90592021-07-019783010.3390/biomedicines9070830Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung CancerClara E. Green0Joseph Clarke1Roy Bicknell2Alice M. Turner3Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKInstitute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UKThe pulmonary endothelium is dysfunctional in chronic obstructive pulmonary disease (COPD), a known risk factor for lung cancer. The pulmonary endothelium is altered in emphysema, which is disproportionately affected by cancers. Gene and microRNA expression differs between COPD and non-COPD lung. We hypothesised that the alteration in microRNA expression in the pulmonary endothelium contributes to its dysfunction. A total of 28 patients undergoing pulmonary resection were recruited and endothelial cells were isolated from healthy lung and tumour. MicroRNA expression was compared between COPD and non-COPD patients. Positive findings were confirmed by quantitative polymerase chain reaction (qPCR). Assays assessing angiogenesis and cellular migration were conducted in Human Umbilical Vein Endothelial Cells (<i>n</i> = 3–4) transfected with microRNA mimics and compared to cells transfected with negative control RNA. Expression of miR-181b-3p, miR-429 and miR-23c (all <i>p</i> < 0.05) was increased in COPD. Over-expression of miR-181b-3p was associated with reduced endothelial sprouting (<i>p</i> < 0.05). miR-429 was overexpressed in lung cancer as well and exhibited a reduction in tubular formation. MicroRNA-driven changes in the pulmonary endothelium thus represent a novel mechanism driving emphysema. These processes warrant further study to determine if they may be therapeutic targets in COPD and lung cancer.https://www.mdpi.com/2227-9059/9/7/830pulmonary endotheliumCOPDlung cancermiRNAmicroarrayangiogenesis
spellingShingle Clara E. Green
Joseph Clarke
Roy Bicknell
Alice M. Turner
Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer
Biomedicines
pulmonary endothelium
COPD
lung cancer
miRNA
microarray
angiogenesis
title Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer
title_full Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer
title_fullStr Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer
title_full_unstemmed Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer
title_short Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer
title_sort pulmonary microrna changes alter angiogenesis in chronic obstructive pulmonary disease and lung cancer
topic pulmonary endothelium
COPD
lung cancer
miRNA
microarray
angiogenesis
url https://www.mdpi.com/2227-9059/9/7/830
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AT josephclarke pulmonarymicrornachangesalterangiogenesisinchronicobstructivepulmonarydiseaseandlungcancer
AT roybicknell pulmonarymicrornachangesalterangiogenesisinchronicobstructivepulmonarydiseaseandlungcancer
AT alicemturner pulmonarymicrornachangesalterangiogenesisinchronicobstructivepulmonarydiseaseandlungcancer