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外泌体传递的致癌性miR-27a与SFRP1结合并促进肾透明细胞癌的血管生成。

Oncogenic miR-27a delivered by exosomes binds to SFRP1 and promotes angiogenesis in renal clear cell carcinoma.

作者信息

Hou Yi, Fan Li, Li Hai

机构信息

Department of Urology, China-Japan Union Hospital of Jilin University, Changchun 130000, P.R. China.

出版信息

Mol Ther Nucleic Acids. 2020 Nov 26;24:92-103. doi: 10.1016/j.omtn.2020.11.019. eCollection 2021 Jun 4.

Abstract

Exosomes derived from cancer cells have emerged as important mediators of malignant phenotypes of tumors, being involved in the transmission of biological signals between cells. Herein, we intended to clarify the role of exosome-mediated transfer of oncogenic microRNA-27a (miR-27a) in angiogenesis of renal clear cell carcinoma (RCCC). Through bioinformatics analysis, we identified the differentially expressed genes of RCCC and predicted miRNAs targeting SFRP1. We manipulated the expression of miR-27a and/or SFRP1 in RCCC cells to explore their roles in angiogenesis through Cell Counting Kit-8 (CCK-8), Transwell, and Matrigel tubule formation assays. miR-27a loaded in exosomes was overexpressed and downregulated and to verify its effect on angiogenesis. SFRP1 was poorly expressed and miR-27a was highly expressed in RCCC tissues, showing a negative correlation. Dual-luciferase assay verified that miR-27a targeted and downregulated SFRP1 expression. Notably, miR-27a enhanced angiogenesis by downregulating SFRP1 expression. miR-27a-loaded exosomes can be delivered from RCCC cells to human umbilical vein endothelial cells (HUVECs). and experiments substantiated that miR-27a-loaded exosomes from RCCC cells repressed SFRP1, augmenting the viability, migration, and angiogenesis of RCCC cells. Together, RCCC-derived miR-27a-loaded exosomes inhibit SFRP1 expression and accelerate tumor angiogenesis in RCCC.

摘要

癌细胞衍生的外泌体已成为肿瘤恶性表型的重要介质,参与细胞间生物信号的传递。在此,我们旨在阐明外泌体介导的致癌性微小RNA-27a(miR-27a)转移在肾透明细胞癌(RCCC)血管生成中的作用。通过生物信息学分析,我们鉴定了RCCC的差异表达基因,并预测了靶向SFRP1的微小RNA。我们在RCCC细胞中调控miR-27a和/或SFRP1的表达,通过细胞计数试剂盒-8(CCK-8)、Transwell和基质胶小管形成试验探索它们在血管生成中的作用。对外泌体中加载的miR-27a进行过表达和下调,以验证其对血管生成的影响。SFRP1在RCCC组织中表达较低,而miR-27a表达较高,呈负相关。双荧光素酶测定证实miR-27a靶向并下调SFRP1表达。值得注意的是,miR-27a通过下调SFRP1表达增强血管生成。加载miR-27a的外泌体可以从RCCC细胞传递到人脐静脉内皮细胞(HUVECs)。实验证实,来自RCCC细胞的加载miR-27a的外泌体抑制SFRP1,增强RCCC细胞的活力、迁移和血管生成。总之,RCCC衍生的加载miR-27a的外泌体抑制SFRP1表达并加速RCCC中的肿瘤血管生成。

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