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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MDPI AG
2021-07-01
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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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id | doaj.art-44b35a3130e84602ac505c05f4c0a91e |
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issn | 2227-9059 |
language | English |
last_indexed | 2024-03-10T09:44:52Z |
publishDate | 2021-07-01 |
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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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