Cancer-associated fibroblast-released extracellular vesicles carrying miR-199a-5p induces the progression of​ gastric cancer through regulation of FKBP5-mediated AKT1/mTORC1 signaling pathway

• Published in: Cell cycle (Georgetown, Tex.) Vol. 21; no. 24; pp. 2590 - 2601
• Main Authors: Wang, Yan, Li, Tao, Yang, Lei, Zhang, Xunlei, Wang, Xiaoli, Su, Xiaoqin, Ji, Congfei, Wang, Zhenxin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 17.12.2022
• Subjects: AKT1; Cancer-associated fibroblasts; Cancer-Associated Fibroblasts - metabolism; Carcinogenesis - pathology; extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - pathology; FKBP5; gastric cancer; Humans; Mechanistic Target of Rapamycin Complex 1 - genetics; Mechanistic Target of Rapamycin Complex 1 - metabolism; microRNA-199a-5p; MicroRNAs - genetics; MicroRNAs - metabolism; mTORC1; Proto-Oncogene Proteins c-akt - metabolism; Research Paper; Signal Transduction; Stomach Neoplasms - pathology; Cancer-associated fibroblasts; extracellular vesicles; gastric cancer; microRNA-199a-5p; AKT1; mTORC1; FKBP5
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2022.2105092

Accumulating evidence has unfolded the significance of extracellular vesicles (EVs) in diseases and cancers. Here, we attempted to discuss the role of cancer-associated fibroblasts (CAFs)-derived EVs containing miR-199a-5p in gastric tumorigenesis. Upregulated miR-199a-5p was first identified in cancer cells. Then, we selected CAFs for isolation of EVs which were co-cultured with AGS cells. We observed successful delivery of miR-199a-5p via CAF-derived EVs. Besides, miR-199a-5p promoted malignant properties of AGS cells. Moreover, miR-199a-5p downregulated FKBP5, leading to upregulated phosphorylation level of AKT1, which promoted the malignant phenotypes of AGS cells by activating mammalian target of rapamycin complex 1(mTORC1). Exosomal miR-199a-5p from CAFs promoted gastric tumorigenesis in vivo. Our findings point toward the critical role of CAFs-derived EVs carrying miR-199a-5p in gastric cancer progression.