Abstract：
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.
摘要：
癌症相关成纤维细胞（CAFs）在各种癌症中发挥肿瘤促进作用，包括乳腺癌.CAFs分泌含有miRNA和蛋白质的外泌体，影响肿瘤微环境。在这项研究中,我们鉴定了CAF衍生的外泌体，将功能性miR-92a从CAF转运至肿瘤细胞，从而增强乳腺癌的侵袭性。CAFs下调乳腺癌细胞中G3BP2的表达，并且在CAF衍生的外泌体中观察到miR-92a水平显著升高。体外和体内实验均表明，miR-92a通过直接靶向G3BP2来增强乳腺癌细胞的迁移和侵袭，从而起到促进肿瘤的miRNA的作用。我们验证了RNA结合蛋白SNRPA促进CAF来源的外泌体miR-92a向乳腺癌细胞的转移。CAF来源的外泌体对G3BP2蛋白的减少将TWIST1释放到细胞核中，促进上皮-间质转化（EMT）并进一步加剧乳腺癌进展。此外，CAF来源的外泌体miR-92a诱导小鼠肿瘤侵袭和转移。总的来说,我们的研究表明,CAF来源的外泌体miR-92a通过降低G3BP2而在乳腺癌细胞的迁移和侵袭中发挥启动子的作用,并且可能是一种潜在的新型乳腺癌肿瘤标志物.
