Exosomal miR-625-3p secreted by cancer-associated fibroblasts in colorectal cancer promotes EMT and chemotherapeutic resistance by blocking the CELF2/WWOX pathway. (December 2022)

• Record Type: Journal Article
• Authors: Zhang, Ying; Yin, Changjun; Wei, Chao; Xia, Shuai; Qiao, Zhu; Zhang, Xue-Wen; Yu, Bin; Zhou, Jun; Wang, Rong
• Is Part Of: Pharmacological research. Volume 186(2022)
• Publication Date: 2022-12
• Subjects: Colorectal cancer -- Micro RNA -- Cancer-associated fibroblast -- Exosomal -- Epithelial-mesenchymal transformation -- Chemotherapeutic resistance; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106534
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Migration, invasion, epithelial-mesenchymal transformation (EMT), and chemotherapeutic resistance are the leading causes of therapeutic failure in people with colorectal cancer (CRC). The migration of exosomal miRNA between cancer cells and the tumor microenvironment is directly associated with malignant behavior in cancer-associated fibroblasts (CAFs). In the context of earlier research, the purpose of the current study was to assess the role and potential mechanism of miR-625-3p released by CAFs in CRC cells. Exosomes were extracted and purified from CAFs conditioned medium by ultracentrifugation. Western blot, immunohistochemistry, CCK-8, transwell assay, H&E staining, Tunnel, real-time PCR, double luciferase assay, RNA-binding protein immunoprecipitation (RIP), and immunofluorescence double staining experiments were used to investigate the effects of CAFs-Exo and miR-625-3p on CRC cell invasion, migration, proliferation, EMT, chemotherapeutic resistance, and molecular mechanisms. The current results indicated that CAFs-Exo was directly internalized by CRC cells, and exosomal miR-625-3p derived from CAFs might promote migration, invasion, EMT and chemotherapeutic resistance in CRC cells by inhibiting the CELF2/WWOX pathway, providing a potential candidate for CRC prediction and treatment. Graphical Abstract: Schematic diagram of mechanisms by which CAFs derived exosome miR-625-3p promote EMT and drug resistance in CRC by inhibiting the CELF2/WWOX pathway. ga1