Exosomal miR-10b-5p mediates cell communication of gastric cancer cells and fibroblasts and facilitates cell proliferation
Ting Yan, Xiaping Wang, Guo‐Hua Wei, Hai Li, Leiyu Hao, Yan Liu, Xinqian Yu, Wei Zhu, Ping Liu, Yichao Zhu, Xin Zhou
Abstract
Tumor microenvironment interacts with gastric cancer (GC) cells and affects tumor development. The communication between GC cells and fibroblasts has not been clearly studied and understood. MiR-10b-5p was found highly expressed in tissue and serum samples of patients with advanced stages (stage III+IV) than that in early stage patients (stage I+II). The expression determination of serum exosomal microRNA was also shown with high expression of miR-10b-5p in GC patients with advanced stages. Dual-luciferase activity assays indicated that miR-10b-5p targeted PTEN in GC cells and KLF11 in fibroblasts. The silence of miR-10b-5p up-regulated the expression of PTEN and repressed PI3K/Akt/mTORC1 signaling in GC cells. Clonogenic assay and MTT assay demonstrated that miR-10b-5p inhibitor could significantly reduce the colony formation and cell viability of GC cells. And the incubation of exosomal miR-10b-5p could increase the proliferation of GC cells. Immunohistochemistry staining revealed that high expression of -SMA was detected in GC tissues with advanced stages. The overexpression of miR-10b-5p down-regulated KLF11 expression and elevated TGFR1 expression in fibroblasts. In addition, miR-10b-5p inhibitor blocked the secretion of TGF1 in GC cells and the directional migration of fibroblasts. Therefore, up-regulated exosomal miR-10b-5p is involved in the interaction of GC cells and fibroblasts in tumor microenvironment via participating in the regulation of TGF signaling pathway.