Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
Department of Medical Oncology, Tumor Hospital Affiliated to Nantong University & Nantong Tumor Hospital, Nantong, P.R. China.
Cell Cycle. 2022 Dec;21(24):2590-2601. doi: 10.1080/15384101.2022.2105092. Epub 2022 Aug 25.
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 . Our findings point toward the critical role of CAFs-derived EVs carrying miR-199a-5p in gastric cancer progression.
越来越多的证据揭示了细胞外囊泡（EVs）在疾病和癌症中的重要作用。在这里，我们试图探讨含有 miR-199a-5p 的癌相关成纤维细胞（CAFs）衍生的 EVs 在胃肿瘤发生中的作用。首先在癌细胞中鉴定到上调的 miR-199a-5p。然后，我们选择 CAFs 分离 EVs，并用其与 AGS 细胞共培养。我们观察到 miR-199a-5p 通过 CAF 衍生的 EVs 成功传递。此外，miR-199a-5p 促进了 AGS 细胞的恶性特性。此外，miR-199a-5p 下调 FKBP5，导致 AKT1 的磷酸化水平上调，通过激活雷帕霉素靶蛋白复合物 1（mTORC1）促进 AGS 细胞的恶性表型。来自 CAFs 的外泌体 miR-199a-5p 促进了胃癌的发生。我们的研究结果表明，携带 miR-199a-5p 的 CAFs 衍生 EVs 在胃癌进展中起着关键作用。
