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 730 sunken lake road 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 nightstick twm-850xl carcinoma, angiogenesis, exosomes, microRNA-21, Sprouty RTK signaling antagonist 1, vascular endothelial growth factor.