Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer

被引：194
作者：
Wang, M. [1 ]
Zhao, C. [1 ]
Shi, H. [1 ]
Zhang, B. [1 ]
Zhang, L. [1 ]
Zhang, X. [1 ]
Wang, S. [2 ]
Wu, X. [1 ]
Yang, T. [1 ]
Huang, F. [1 ]
Cai, J. [1 ]
Zhu, Q. [1 ]
Zhu, W. [1 ]
Qian, H. [1 ]
Xu, W. [1 ]
机构：
[1] Jiangsu Univ, Sch Med Sci & Lab Med, Zhenjiang 212013, Jiangsu, Peoples R China
[2] First Peoples Hosp Zhenjiang, Dept Surg, Zhenjiang 212001, Jiangsu, Peoples R China
来源：
BRITISH JOURNAL OF CANCER | 2014年 / 110卷 / 05期
基金：
中国国家自然科学基金;
关键词：
TUMOR MICROENVIRONMENT; EXOSOMES; PROGRESSION; EXPRESSION; HALLMARKS; PATHWAYS; STROMA; ROLES;
D O I：
10.1038/bjc.2014.14
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: MicroRNAs (miRNAs) are involved in gastric cancer development and progression. However, the expression and role of miRNAs in gastric cancer stromal cells are still unclear. Methods: The miRNAs differentially expressed in gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) relative to adjacent non-cancerous tissue-derived MSCs (GCN-MSCs) and in cancer tissues relative to adjacent non-cancerous tissues were screened using miRNA microarray and validated by quantitative RT-PCR. The impact of GC-MSCs on HGC-27 cells was observed in vitro using colony formation and transwell assays, and these cells were subcutaneously co-injected into mice to assess tumour growth in vivo. Exogenous downregulation of miR-221 expression in cells was achieved using an miRNA inhibitor. Results: miR-214, miR-221 and miR-222 were found to be commonly upregulated in GC-MSCs and cancer tissues. Their levels were tightly associated with lymph node metastasis, venous invasion and the TNM stage. Gastric cancer tissue-derived mesenchymal stem cells significantly promoted HGC-27 growth and migration and increased the expression of miR-221 via paracrine secretion, and the targeted inhibition of miR-221 in GC-MSCs could block its tumour-supporting role. GC-MSC-derived exosomes were found to deliver miR-221 to HGC-27 cells and promoted their proliferation and migration. Conclusions: Gastric cancer tissue-derived mesenchymal stem cells favour gastric cancer progression by transferring exosomal miRNAs to gastric cancer cells, thus providing a novel mechanism for the role of GC-MSCs and new biomarkers for gastric cancer.
引用
收藏
页码：1199 / 1210
页数：12
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