miR-374 mediates the malignant transformation of gastric cancer-associated mesenchymal stem cells in an experimental rat model

Ji,Runbi; Zhang,Xu; Qian,Hui; Gu,Hongbing; Sun,Zixun; Mao,Fei; Yan,Yongmin; Chen,Jingyan; Liang,Zhaofeng; Xu,Wenrong

doi:10.3892/or.2017.5831

miR-374 mediates the malignant transformation of gastric cancer-associated mesenchymal stem cells in an experimental rat model

Authors:
- Runbi Ji
- Xu Zhang
- Hui Qian
- Hongbing Gu
- Zixun Sun
- Fei Mao
- Yongmin Yan
- Jingyan Chen
- Zhaofeng Liang
- Wenrong Xu
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Affiliations: Department of Clinical Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
Published online on: July 18, 2017 https://doi.org/10.3892/or.2017.5831
Pages: 1473-1481
Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mesenchymal stem cells (MSCs) are a critical component of the tumor microenvironment. Upon distinct pathological stimulus, MSCs show phenotypic and functional changes. Gastric cancer is one of the leading causes of cancer‑related deaths worldwide. The roles and mechanisms of MSCs in gastric cancer have not been well characterized. In the present study, we investigated the roles of MSCs in the malignant transformation from gastritis to gastric cancer using an N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer model. We isolated MSCs from the gastric tissues of normal (RGN-MSCs) and MNNG-exposed rats (RGI-MSCs), and compared the biological properties of RGI-MSCs with RGN-MSCs. We found that RGI-MSCs had increased proliferative and migratory capabilities than these capacities noted in the RGN-MSCs. In addition, RGI-MSCs produced higher levels of IL-6, CXCL10 and MCP-1 than RGN-MSCs. Moreover, RGI-MSCs promoted the migration of normal gastric mucosa epithelial cells by inducing epithelial-mesenchymal transition (EMT). The upregulation of miR-374 in RGI-MSCs was partially responsible for their increased proliferative and migratory capabilities. Collectively, our findings provide new evidence for the roles of MSCs in gastric carcinogenesis, suggesting that targeting gastric cancer-associated MSCs may represent a novel avenue for gastric cancer therapy.

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