Human umbilical vein endothelial cells-derived microRNA-203-containing extracellular vesicles alleviate non-small-cell lung cancer progression through modulating the DTL/p21 axis

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and is characterized by extensive metastasis and poor prognosis. Extracellular vesicles (EVs) derived from endothelial cells carrying microRNAs (miRNAs/miRs) have diagnostic and therapeutic potential for NSCLC. We herein investigate the potential of EVs derived from human umbilical vein endothelial cells (HUVECs) to transfer miR-203 to affect the progression of NSCLC. miR-203 and p21 were poorly expressed while DTL was highly expressed both in NSCLC tissues and cell lines. We employed CCK-8 proliferation, colony formation, and Transwell migration and invasion assays to evaluate the effects of miR-203 on NSCLC cell behaviors using loss- and gain-function approaches. EVs were isolated from HUVECs and then co-cultured with the A549 cells transfected with mimic-NC or miR-203 inhibitor. miR-203 targeted DTL and downregulated its expression, subsequently leading to increased stability of p21 which is a tumor suppressor. EV-enriched miR-203 from HUVECs suppressed malignant phenotypes of NSCLC cells and delayed tumor growth. In conclusion, miR-203 from HUVEC-derived EVs exerts inhibitory effects on the progression of NSCLC by targeting DTL and promoting p21 protein stability.