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

Autor: Sheng Z; 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., Wang X; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Ding X; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Zheng Y; Department of Pathology, Weifang people's Hospital, Weifang, Shandong, China., Guo A; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Cui J; Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China., Ma J; Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China., Duan W; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Dong H; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Zhang H; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Cui M; Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China., Su W; Department of Physiology, Second Medical University, Weifang, Shandong, China., Zhang B; 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. Electronic address: Zhangbg@wfmc.edu.cn.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2024 Jul; Vol. 119, pp. 111182. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1016/j.cellsig.2024.111182
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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