ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2021; 12(7):2140-2150. doi:10.7150/jca.47817 This issue Cite
Research Paper
Exosomal miR-10b-5p mediates cell communication of gastric cancer cells and fibroblasts and facilitates cell proliferation
1. Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China.
2. Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
3. Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
4. Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
5. Department of Physiology, Nanjing Medical University, Nanjing 211166, China.
6. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
7. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
#These authors contributed equally to this work.
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 α-SMA was detected in GC tissues with advanced stages. The overexpression of miR-10b-5p down-regulated KLF11 expression and elevated TGFβR1 expression in fibroblasts. In addition, miR-10b-5p inhibitor blocked the secretion of TGFβ1 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 TGFβ signaling pathway.
Keywords: miR-10b-5p, exosome, gastric cancer, cell proliferation, fibroblast
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