miRNA-206 regulates human pulmonary microvascular endothelial cell apoptosis via targeting in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death due to tis high morbidity and mortality. microRNAs have emerged as new biomarkers for the prognosis and diagnosis of patients with COPD. In this study, we aimed to investigate the expression of microRNA-206 (miR-206) in lung tissues from COPD patients and to explore the regulatory role of miR-206 in the human pulmonary microvascular endothelial cells (HPMECs). Our results showed that cigarette smoke extract (CSE) promoted cell apoptosis, increased caspase-3 activity, and upregulated the expression of miR-206 in HPMECs, which was significantly reversed by the miR-206 knockdown. Transfection with miR-206 mimics led to cell apoptosis and was closely related to changes in the protein expression levels of caspase-3, caspase-9, and Bcl-2 in HPMECs. Further bioinformatics prediction analysis revealed that the 3 '-untranslated region (3 ' UTR) of Notch3 and vascular endothelial growth factor-A (VEGFA) harbored miR-206-binding sites, and overexpression of miR-206 repressed the luciferase activity of the vectors containing Notch3 and VEGFA 3 ' UTR. Overexpression of either Notch3 or VEGFA attenuated miR-206-induced cell apoptosis in HPMECs. More importantly, miR-206 expression was upregulated in the lung tissues from COPD patients and was positively corrected with forced expiratory volume 1% predicted in COPD patients, while Notch3 and VEGFA mRNA levels were downregulated and were negatively correlated with the expression level of miR-206 in the lung tissues from COPD patients. In conclusion, our results showed that miR-206 was upregulated in COPD patients and CSE-treated HPMECs, promoted cell apoptosis via directly targeting Notch3 and VEGFA in HPMECs.