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

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.

SUBMITTER: Zhuang H

PROVIDER: S-EPMC7604463 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhuang Huirong H Wang Hongjun H Yang Haibo H Li Hongli H

Cancer management and research 20201028

<h4>Objective</h4>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.<h4>Materials and methods</h4>Initially, the expression patterns of miR-21, SPRY1, and VEGF were determined in ESCC tissues and cells. The relationship between miR-21 and SP ...[more]

PMID: 33149673

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Project description:BackgroundDue to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1.MethodsTMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue (TB), immunohistochemical (IHC) staining, Western blotting (WB) and RT-qPCR. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. WB, RT-qPCR, IHC and TB were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo chorioallantoic membrane (CAM) assay and WB.ResultsIn the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged, and miR-21-5p and UAC model were shown to affect the expression of Spry1, IL-1β, MMP-13, and VEGF. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1β, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway.ConclusionThis study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.

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Dataset Information

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

Publications

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

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