Cancer Management and Research (Oct 2020)
Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1
Abstract
Huirong Zhuang,1 Hongjun Wang,2 Haibo Yang,2 Hongli Li1 1Operating Room, East Medical District of Linyi People’s Hospital, Linyi 276034, People’s Republic of China; 2Department of Occupational Disease, Linyi People’s Hospital, Linyi 276000, People’s Republic of ChinaCorrespondence: Hongli LiOperating Room, East Medical District of Linyi People’s Hospital, No. 233, Fenghuang Street, Hedong District, Linyi, Shandong Province 276034, People’s Republic of ChinaTel +86-539-8096762Email [email protected]: Esophageal squamous cell carcinoma (ESCC) persists among the most prevalent cancers worldwide. Angiogenesis represents a crucial element necessitated for tumor growth and metastasis in ESCC. In this study, we aimed to study the effect of microRNA (miR)-21 on angiogenesis in ESCC and its underlying mechanism.Materials and Methods: Initially, the expression patterns of miR-21, SPRY1, and VEGF were determined in ESCC tissues and cells. The relationship between miR-21 and SPRY1 was identified using dual-luciferase reporter assay. Exosomes were subsequently isolated from the ESCC cells, followed by co-culture with the human umbilical venous endothelial cells (HUVECs). HUVEC proliferation and angiogenesis were determined by means of CCK-8, colony formation, and microtubule formation in vitro. Chicken chorioallantoic membrane (CAM) model and mouse xenograft model of ESCC cells were established to substantiate the function of miR-21 corresponding to the angiogenesis and tumor growth of ESCC, followed by microvascular density (MVD) evaluation.Results: Expression patterns of miR-21 and VEGF were elevated, while the SPRY1 expression pattern was repressed in ESCC tissues and cells. The downregulation of miR-21 and exosome-derived miR-21 impeded the proliferation and angiogenesis in HUVECs. Our data revealed that miR-21 could negatively target SPRY1, and positively target VEGF. The downregulation of miR-21 could evidently encumber the angiogenesis and tumor growth of ESCC in vivo, as evidenced by the decrease in number of branches of the microvessels and MVD.Conclusion: Collectively, ESCC cell-derived exosome containing miR-21 promotes the proliferation and angiogenesis of HUVECs via SPRY1 downregulation and VEGF upregulation.Keywords: esophageal squamous cell carcinoma, angiogenesis, exosomes, microRNA-21, Sprouty RTK signaling antagonist 1, vascular endothelial growth factor
