Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth

The current study tried to elucidate the regulatory role of tumor cell-derived exosomes (Exos)-circ_0064516 in angiogenesis and growth of cervical cancer. Related cirRNAs and downstream target genes were identified through bioinformatics analysis. Exos were isolated from cervical cancer cell line CaSki, followed by co-cultured with human umbilical vein endothelial cells (HUVECs). Then, the roles of circ_0064516, miR-6805-3p, and MAPK1 in migration and angiogenesis of HUVECs were assayed. Furthermore, xenografted tumors were transplanted into nude mice for in vivo validation. In vitro assay validated highly expressed circ_0064516 in cervical cancer cells. Tumor cell-derived Exos carried circ_0064516 to HUVECs. circ_0064516 increased MAPK1 expression by binding to miR-6805-3p, thus enhancing migration and angiogenesis. Exos containing circ_0064516 also promoted tumorigenesis of cervical cancer cells in nude mice. We confirmed the oncogenic role of tumor cell-derived Exos carrying circ_0064516 in cervical cancer progression through miR-6805-3p/MAPK1.

本研究旨在阐明肿瘤细胞来源的外泌体（exosomes, Exos）携带的circ_0064516在宫颈癌血管生成与肿瘤生长中的调控作用。通过生物信息学分析筛选相关环状RNA（circRNAs）及下游靶基因。从宫颈癌细胞系CaSki中分离外泌体，与人脐静脉内皮细胞（human umbilical vein endothelial cells, HUVECs）进行共培养。随后检测circ_0064516、miR-6805-3p及MAPK1对HUVEC迁移与血管生成的调控作用。进一步将移植瘤接种至裸鼠体内开展体内验证实验。体外实验证实circ_0064516在宫颈癌细胞中呈高表达状态。肿瘤细胞来源的外泌体可将circ_0064516递送至HUVECs。circ_0064516通过靶向结合miR-6805-3p上调MAPK1的表达水平，进而增强HUVEC的迁移能力与血管生成能力。携带circ_0064516的外泌体还可促进裸鼠体内宫颈癌细胞的致瘤活性。本研究证实，肿瘤细胞来源的外泌体通过携带circ_0064516，经由miR-6805-3p/MAPK1信号轴在宫颈癌进展中发挥致癌功能。