Details

Autor(en) / Beteiligte

• Sheng, Zhimei
• Wang, Xuejie
• Ding, Xiaodi
• Zheng, Yuanhang
• Guo, Ai
• Cui, Jiayu
• Ma, Jing
• Duan, Wanli
• Dong, Hao
• Zhang, Hongxing
• Cui, Meimei
• Su, Wenxia
• Zhang, Baogang

Titel

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2

Ist Teil von

• Cellular signalling, 2024-07, Vol.119, p.111182-111182, Article 111182

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •CAF-derived exosomes deliver functional miR-92a to breast cancer cells, enhancing breast cancer aggressiveness.•CAF-derived exosomal miR-92a promotes breast cancer cell migration and invasion through G3BP2 binding.•RNA-binding protein SNRPA facilitates CAF-derived exosomal miR-92a transfer to breast cancer cells.•CAF-derived exosomal miR-92a induces EMT, promoting breast cancer deterioration.•CAF-derived exosomal miR-92a induces mouse tumor metastasis and could be a new breast cancer marker.