微泡
癌相关成纤维细胞
乳腺癌
癌症研究
转移
外体
肿瘤微环境
小RNA
癌细胞
癌症
肿瘤进展
细胞迁移
生物
上皮-间质转换
医学
细胞
内科学
肿瘤细胞
基因
生物化学
遗传学
作者
Zhimei Sheng,Xuejie Wang,Xiaodi Ding,Yuanhang Zheng,Ai Guo,Jing Cui,Juan Ma,Wanxing Duan,Hongbiao Dong,Hongxing Zhang,Ming Cui,Wenxia Su,Baogang Zhang
标识
DOI:10.1016/j.cellsig.2024.111182
摘要
Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.
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