<p>Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1</p>

Abstract

Objective 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.

RETRACTED ARTICLE: microRNA-10a-5p from gastric cancer cell-derived exosomes enhances viability and migration of human umbilical vein endothelial cells by targeting zinc finger MYND-type containing 11

“…CCK-8 kit (MAO218, Meilun Biomeilunbio® Company, Dalian, China) was used. After seeding in 96-well plates, HUVECs were added with 10% CCK-8 reagent on the 1, 2, 3, 4, and 5 d, and incubated for 2 h. A microplate reader (Stat Fax 2100; Awareness, USA) was employed to measure the optical density 450 nm [ 23 ].…”

Small Extracellular Vesicles in the Development, Diagnosis, and Possible Therapeutic Application of Esophageal Squamous Cell Carcinoma

“…For example, compared with normal exosomes, hypoxic exosomes have played a unique role in facilitating the aggressive behavior of human umbilical vein endothelial cells (HUVECs) both in vitro and in vivo , and HUVECs exposed to hypoxic exosomes induce enhanced proliferation, metastatic dissemination, and vessel formation ability in ESCC ( 86 ). Consistent with that study, Zhuang showed that ESCC cell-derived exosomal miRNA-21 potentiates the angiogenesis ability of HUVEC by targeting sprouty RTK signaling antagonist 1 (SPRY1) in ESCC ( 60 ). Moreover, exosomal miRNA-21-5p has been shown to significantly promote the angiogenesis of targeted cells via the activation of programmed cell death 4 and downgrading of the signaling pathway or the PTEN/Akt signal pathway in ESCC ( 59 ).…”

Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells

“…Among the biomolecules carried by EVs, miRNAs have been found to play roles in tumor-induced inflammation, angiogenesis and immune modulation to facilitate tumor spreading, and tumor escape from immune surveillance [ 34 ]. Modulation of cellular miR-21 levels has been shown to cause changes in chemo-sensitivity [ 31 ], however direct evidence of EV-mediated modulation of chemo-sensitivity via miR-21 expression remains elusive, in contrast to the more widely available indirect evidence based on cancer cell proliferation rates [ 35 ]. Ren and colleagues verified that EVs from hypoxic mesenchymal stem cells promote NSCLC growth by delivering miR-21, which downregulates PTEN [ 36 ].…”