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

  • Cell Cycle. 2022 Aug 25;1-12. doi: 10.1080/15384101.2022.2105092.
Yan Wang  1  2 ,  Tao Li  2 ,  Lei Yang  2 ,  Xunlei Zhang  2 ,  Xiaoli Wang  2 ,  Xiaoqin Su  2 ,  Congfei Ji  2 ,  Zhenxin Wang  1
Affiliations
  • 1. Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
  • 2. Department of Medical Oncology, Tumor Hospital Affiliated to Nantong University & Nantong Tumor Hospital, Nantong, P.R. China.
PMID: 36005478 DOI: 10.1080/15384101.2022.2105092
Abstract

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.

Keywords
AKT1; Cancer-associated fibroblasts; FKBP5; extracellular vesicles; gastric cancer; mTORC1; microRNA-199a-5p.
Products