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

Abstract

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 (n = 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 p < 0.05) was increased in COPD. Over-expression of miR-181b-3p was associated with reduced endothelial sprouting (p < 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.

Endothelial-mesenchymal transition induced by metastatic 4T1 breast cancer cells in pulmonary endothelium in aged mice

“…The injection of 4T1 breast cancer cells did not affect plasma concentration of the following biomarkers of endothelial dysfunction: SDC-1, ESM-1, sVCAM-1, sICAM-1, sE-sel, t-PA, sP-sel, sTie-2, Ang-2, and sFLT (results not shown). Finally, we evaluated plasma expression levels of miR-29a-3p and miR-181b-3p which might affect EndMT progression ( Srivastava et al, 2019 ; Green et al, 2021 ). Plasma expression of miR-29a-3p and miR-181-b-3p was lower in 40-week-old mice than in 20-week-old mice two days post-injection ( Figure 6E ).…”

Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review

“…Notably, these four miRNAs have been previously described as anti-angiogenic miRNAs ( Zhao et al, 2017 ; Dong et al, 2019 ; Tang et al, 2020 ; Witvrouwen et al, 2021 ). Furthermore, anti-angiogenic miRNAs, miR-206, miR-320, miR-365, miR-181b, and miR-24 were overexpressed in PE; however, miR-181b and miR-24 were anti-inflammatory in previous studies ( Wu et al, 2014 ; Fu et al, 2016 ; Liang et al, 2016 ; Xu et al, 2020 ; Green et al, 2021 ; Liu and Li, 2021 ; Wu et al, 2021 ; Yuan et al, 2021 ). The anti-inflammatory miRNAs (miR-24 and miR-130a) and pro-inflammatory miR-29b were repressed and overexpressed in COVID-19, respectively, consistent with their roles ( Lorenzen et al, 2014 ; Zheng et al, 2016 ; Chen et al, 2020 ).…”

Chronic Obstructive Pulmonary Disease: The Present and Future

“…Frequent exacerbator LABA, LAMA, ICS, roflumilast, macrolides Optimisation of comorbid physical and mental health conditions [27] Chronic bronchitis Roflumilast, mucolytics Use of CFTR modulators [13] Emphysema Lung volume reduction surgery Correction of miR overexpression [8] Type 1 respiratory failure Long-term oxygen therapy Increased vigilance for VTE in acute illness [29] Type 2 respiratory failure Domiciliary NIV Consideration of comorbidities such as OSA/ORRF [21] Eosinophilic COPD Steroids Identification of distinct microbiome in eosinophil-predominant COPD [15] Investigation of immunomodulatory alternatives to steroids [30] Bronchiectasis Targeted antibiotics, chest physiotherapy Identify severity clusters using biomarkers, to stratify follow-up and hospitalisation [33] α-1 antitrypsin deficiency LABA, LAMA, ICS α-1 antitrypsin augmentation therapy [17] Subgroups requiring further study Biomass and pollutant COPD Removal of pollutant exposure Use of predictive machine-learning to target individuals at greatest risk of pollutant-induced emphysema [31] Premalignant COPD Smoking cessation…”

“…An included study by Green et al compares microRNA targets between tumour and non-tumour lung tissues from a mixture of COPD and non-COPD patients [ 8 ]. Green et al identified that several microRNA targets were upregulated in tumours, including targets previously associated with non-pulmonary smoking-related cancers.…”