Exosomes miR-24-3p Target S1PR1 to Promote Angiogenesis and Induce Tumor Metastasis in non-small cell lung cancer

Abstract

Abstract Background Angiogenesis is critical to the growth and metastasis of malignant tumors. The aim of this study is to investigate the molecular mechanism of exosome miR-24-3p in angiogenesis and metastasis of non-small cell lung cancer (NSCLC). Materials and methods Plasma samples of 60 patients with confirmed NSCLC, 20 patients with benign lung disease, 20 healthy controls, and cancer and paracancerous tissues of 12 NSCLC patients were collected in authors’ hospital from June 2020 to December 2020 for the screening of reliable exocytotic microRNAs. Six cell lines were used to investigate the effect of exosome-derived miR-24-3p on vascular endothelial cells in tumors to clarify the pathways promoting tumor migration and proliferation. Animal experiments were conducted to further verify the function of miR-24-3p. Results The expression levels of miR-24-3p in plasma extracellular vesicles of NSCLC patients were significantly increased and correlated positively with disease stage. The miR-24-3p promoted angiogenesis and increased vascular permeability by inhibiting the expression of sphingosinel-phosphate receptor 1(S1PR1) in endothelial cells, indicating S1PR1 is a downstream target gene of miR-24-3p, which binds to the S1PR1 3’- UTR region. Conclusions Tumor-derived exosome miR-24-3p could enter vascular endothelial cells and promote angiogenesis and vascular permeability in NSCLC, which also enter the circulatory system to improve the pre-metastasis microenvironment in distant organs and ultimately promote the occurrence of tumor metastasis. miR-24-3p is a promising potential molecular biomarker and new drug therapeutic target for patients with NSCLC.