Journal
BRITISH JOURNAL OF CANCER
Volume 110, Issue 5, Pages 1199-1210Publisher
SPRINGERNATURE
DOI: 10.1038/bjc.2014.14
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Funding
- Major Research Plan of the National Natural Science Foundation of China [91129718]
- National Natural Science Foundation of China [81071421, 81302119]
- Jiangsu Province's Project of Scientific and Technological Innovation and Achievements Transformation [BL2012055]
- Jiangsu Province's Outstanding Medical Academic Leader and Sci-tech Innovation Team Program [LJ201117]
- Natural Science Foundation of the Jiangsu Province [BK2012709, BK20130540]
- Doctoral Program Foundation of State Education Ministry [20113227110011]
- Jiangsu Province for Natural Scicence Research in Colleges and Universities [13KJB320001]
- Scientific Research Foundation of Jiangsu University for Senior Professional Talents [13JDG088]
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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.
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