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研究源自舌鳞状细胞癌细胞的外泌体miR-205-5p是否通过靶向AMOT刺激人脐静脉内皮细胞的血管生成活性。

Investigating whether exosomal miR-205-5p derived from tongue squamous cell carcinoma cells stimulates the angiogenic activity of HUVECs by targeting AMOT.

作者信息

Huang Wenxi, Zeng Zanwen, Xu Yonghui, Mai Zhibin

机构信息

Stomatology Department, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China.

Thyroid and Vascular Department, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China.

出版信息

Cancer Biomark. 2023;38(2):215-224. doi: 10.3233/CBM-220350.

Abstract

BACKGROUND

Although exosomal microRNAs (exo-miRNAs) regulate angiogenesis, they are not sufficient for the development of anti-vascular drugs for tongue squamous cell carcinoma (TSCC). miR-205-5p is an exo-miRNA that is highly expressed in the saliva of patients with oral SCC.

OBJECTIVE

We aimed to clarify the role and molecular mechanism of exosomal miR-205-5p in regulating TSCC angiogenesis.

METHODS

Effect of exosomes derived from TSCC cells on human umbilical vein endothelial cell (HUVEC) function was determined using the CCK-8, Transwell, Transwell-Matrigel, and Matrigel-based tube formation assays. Protein levels were detected by western blot. The binding between miR-205-5p and the 3'UTR of AMOT was verified using a luciferase reporter assay.

RESULTS

Exosomal miR-205-5p (exo-miR-205-5p) promoted the proliferation, migration, and invasion of HUVECs, increased the number of tubes formed by HUVECs, and increased the vascular endothelial growth factor receptor 2 levels in HUVECs. Exo-miR-205-5p downregulated the AMOT level in HUVECs. Results of the luciferase reporter assay showed that miR-205-5p could bind to the 3'UTR of AMOT. AMOT overexpression blocked the effect of exo-miR-205-5p on HUVEC functions.

CONCLUSION

Exo-miR-205-5p derived from TSCC regulates the angiogenic activity of HUVECs by targeting AMOT and might be a new molecular target for the development of anti-vascular drugs for TSCC.

摘要

背景

尽管外泌体微小RNA(外泌体miRNA)可调节血管生成,但它们不足以用于开发针对舌鳞状细胞癌(TSCC)的抗血管生成药物。miR-205-5p是一种在外口腔鳞状细胞癌患者唾液中高表达的外泌体miRNA。

目的

我们旨在阐明外泌体miR-205-5p在调节TSCC血管生成中的作用及分子机制。

方法

使用CCK-8、Transwell、Transwell-基质胶和基于基质胶的管形成实验,确定TSCC细胞来源的外泌体对人脐静脉内皮细胞(HUVEC)功能的影响。通过蛋白质印迹法检测蛋白质水平。使用荧光素酶报告基因实验验证miR-205-5p与AMOT的3'非翻译区(3'UTR)之间的结合。

结果

外泌体miR-205-5p(外泌体miR-205-5p)促进了HUVEC的增殖、迁移和侵袭,增加了HUVEC形成的管的数量,并提高了HUVEC中血管内皮生长因子受体2的水平。外泌体miR-205-5p下调了HUVEC中的AMOT水平。荧光素酶报告基因实验结果表明,miR-205-5p可与AMOT的3'UTR结合。AMOT过表达阻断了外泌体miR-205-5p对HUVEC功能的影响。

结论

TSCC来源的外泌体miR-205-5p通过靶向AMOT调节HUVEC的血管生成活性,可能是开发TSCC抗血管生成药物的新分子靶点。

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