Exosomal microRNA-23b-3p promotes tumor angiogenesis and metastasis by targeting PTEN in salivary adenoid cystic carcinoma

血管生成 微泡 张力素 癌症研究 腺样囊性癌 转移 PTEN公司 间质细胞 生物 小RNA 下调和上调 肿瘤进展 血管通透性 癌症 病理 医学 细胞生物学 信号转导 PI3K/AKT/mTOR通路 基因 遗传学 生物化学
作者
Chen‐Xing Hou,Nannan Sun,Wei Han,Ying Meng,Chen-Xing Wang,Quing Zhu,Yuting Tang,Jinhai Ye
出处
期刊:Carcinogenesis [Oxford University Press]
卷期号:43 (7): 682-692 被引量:14
标识
DOI:10.1093/carcin/bgac033
摘要

MicroRNA (miR)-23b-3p is known to target various genes that are involved in cancer-related pathways. Exosomes are emerging intercellular communication agents. Exosomes secreted by cancer cells can deliver active molecules to the surrounding stromal cells, thereby influencing the recipient cells and promoting the development of cancers. However, the role of exosomal miR-23b-3p in salivary adenoid cystic carcinoma (SACC) is not yet clear. In this study, we set out to investigate the potential role of cancer-derived exosomal miR-23b-3p-related phosphatase and tensin homolog deleted on chromosome 10 in the alteration of angiogenesis and vascular permeability in SACC. We investigated the effect of exosomal miR-23b-3p on the progression of SACC. In vitro experiments indicated that exosomal miR-23b-3p led to an upregulation of vascular permeability, and reduced expression of tight junction proteins. In addition, exosomal miR-23b-3p also enhanced angiogenesis and migration. Next, the angiogenic effect of exosomal miR-23b-3p was validated in vivo, as it led to an increase in the tumor microvasculature. Furthermore, the growth rate of SACC was faster after injection of exosomes loaded with cholesterol-modified miR-23b-3p in mice. In conclusion, these results revealed that SACC cell-derived exosomes play an important role in promoting angiogenesis and local vascular microleakage of SACC by transporting miR-23b-3p, which suggests that miR-23b-3p in the exosomes may be a potential biomarker for distant metastasis of SACC. This suggests the potential of a novel therapeutic target by delivering anti-miR-23b-3p that focuses on exosomes.
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