Human umbilical vein endothelial cells-derived microRNA-203-containing extracellular vesicles alleviate non-small-cell lung cancer progression through modulating the DTL/p21 axis
- 8 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Gene Therapy
- Vol. 29 (1), 87-100
- https://doi.org/10.1038/s41417-020-00292-3
Abstract
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.This publication has 45 references indexed in Scilit:
- Association between downexpression of MiR-203 and poor prognosis in non-small cell lung cancer patientsClinical and Translational Oncology, 2015
- MicroRNA-203 Regulates Growth and Metastasis of Breast CancerCellular Physiology and Biochemistry, 2015
- Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrinsJournal of Controlled Release, 2015
- Regulation of cancer metastasis by microRNAsJournal of Biomedical Science, 2015
- Long Noncoding RNA ANRIL Promotes Non–Small Cell Lung Cancer Cell Proliferation and Inhibits Apoptosis by Silencing KLF2 and P21 ExpressionMolecular Cancer Therapeutics, 2015
- Cancer cells remodel themselves and vasculature to overcome the endothelial barrierCancer Letters, 2014
- The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligaseOncotarget, 2014
- CXCR2 Macromolecular Complex in Pancreatic Cancer: A Potential Therapeutic Target in Tumor GrowthTranslational Oncology, 2013
- PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complexGenes & Development, 2008
- The Cell Cycle Inhibitor p21 Binds to the myc and cdc25A Promoters upon DNA Damage and Induces Transcriptional RepressionPublished by Elsevier BV ,2006