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肿瘤来源的外泌体FGD5-AS1通过靶向miR-6838-5p/VAV2轴促进甲状腺癌的血管生成、血管通透性和转移。

Tumor-Derived Exosome FGD5-AS1 Promotes Angiogenesis, Vascular Permeability, and Metastasis in Thyroid Cancer by Targeting the miR-6838-5p/VAV2 Axis.

作者信息

Liu Bo, Chen Jiaming, Shang Fangjian, Lian Meng, Shen Xixi, Fang Jugao

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

Department of General Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, China.

出版信息

J Oncol. 2022 Apr 29;2022:4702855. doi: 10.1155/2022/4702855. eCollection 2022.

Abstract

Exosomes are small vesicles with a diameter of 30~150 nm secreted by cells, which are rich in mRNA, microRNA, and long noncoding RNA (lncRNA). The biological functions of most exosomal lncRNAs are not well understood. Studies have shown that tumor exosome FGD5-AS1 plays an important role in the proliferation, migration, and invasion of tumor cells. In this study, SW1736 and KAT18 TC cells with high expression of FGD5-AS1 were screened. Exosomes with high expression of FGD5-AS1 were collected. The collected exosomes were then added to HUVEC cells. After incubation for 24 h, the effects on the proliferation and migration of HUVEC cells and vascular permeability were detected. The results showed that TC cells SW1736 and KAT18 could secrete a large number of exosomes, which could be taken up by HUVEC cells. Overexpression of FGD5-AS1 enhanced proliferation, migration, angiogenesis, and permeability of HUVEC. This effect is achieved through activation of the miR-6838-5p/VAV2 axis. These results suggest that FGD5-AS1 in tumor-derived exoskeleton promotes angiogenesis, vascular permeability, and metastasis by regulating the endothelial miR-6838-5p/VAV2 axis and ultimately promotes the occurrence and development of TC.

摘要

外泌体是细胞分泌的直径为30~150纳米的小囊泡,富含信使核糖核酸(mRNA)、微小核糖核酸(microRNA)和长链非编码核糖核酸(lncRNA)。大多数外泌体lncRNA的生物学功能尚不清楚。研究表明,肿瘤外泌体FGD5-AS1在肿瘤细胞的增殖、迁移和侵袭中起重要作用。在本研究中,筛选出FGD5-AS1高表达的SW1736和KAT18甲状腺癌细胞(TC)。收集FGD5-AS1高表达的外泌体。然后将收集的外泌体添加到人脐静脉内皮细胞(HUVEC)中。孵育24小时后,检测其对HUVEC细胞增殖、迁移及血管通透性的影响。结果显示,TC细胞SW1736和KAT18可分泌大量外泌体,且能被HUVEC细胞摄取。FGD5-AS1的过表达增强了HUVEC细胞的增殖、迁移、血管生成及通透性。这种作用是通过激活微小核糖核酸-6838-5p/鸟嘌呤核苷酸交换因子2(miR-6838-5p/VAV2)轴实现的。这些结果表明,肿瘤来源外泌体中的FGD5-AS1通过调节内皮细胞miR-6838-5p/VAV2轴促进血管生成、血管通透性及转移,最终促进甲状腺癌的发生发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30dd/9076303/f034723d87d0/JO2022-4702855.001.jpg

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