外泌体 miR-92a 来源于癌症相关成纤维细胞,通过调控 G3BP2 促进乳腺癌的侵袭和转移。
Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.
机构信息
Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China; Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China.
Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China.
出版信息
Cell Signal. 2024 Jul;119:111182. doi: 10.1016/j.cellsig.2024.111182. Epub 2024 Apr 17.
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.
癌症相关成纤维细胞(CAFs)在多种癌症中发挥促肿瘤作用,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。在本研究中,我们鉴定了 CAF 来源的外泌体,这些外泌体将功能性 miR-92a 从 CAFs 转运到肿瘤细胞,从而增强乳腺癌的侵袭性。CAFs 下调乳腺癌细胞中 G3BP2 的表达,并且观察到 CAF 来源的外泌体中 miR-92a 水平显著升高。体内外实验均表明,miR-92a 通过直接靶向 G3BP2 增强乳腺癌细胞的迁移和侵袭,作为一种促瘤 miRNA 发挥作用。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 来源的外泌体减少 G3BP2 蛋白,将 TWIST1 释放到细胞核中,促进上皮-间充质转化(EMT),进一步加重乳腺癌的进展。此外,CAF 来源的外泌体 miR-92a 诱导小鼠肿瘤侵袭和转移。总之,我们的研究表明,CAF 来源的外泌体 miR-92a 通过减少 G3BP2 促进乳腺癌细胞的迁移和侵袭,可能成为乳腺癌的潜在新型肿瘤标志物。