Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer.
Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer.
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胃癌组织来源的间充质干细胞中失调的 microRNA：新型生物标志物和胃癌的机制
DOI：
10.1038/bjc.2014.14
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发表时间：
2014-03-04
影响因子：
8.8
通讯作者：
Xu, W.
中科院分区：
文献类型：
--
作者：
Wang, M.;Zhao, C.;Shi, H.;Zhang, B.;Zhang, L.;Zhang, X.;Wang, S.;Wu, X.;Yang, T.;Huang, F.;Cai, J.;Zhu, Q.;Zhu, W.;Qian, H.;Xu, W.
背景：microRNAs（miRNAs）参与胃癌的发生、发展。方法：采用miRNA芯片技术筛选胃癌组织间充质干细胞（GC-MSCs）与癌旁组织间充质干细胞（GCN-MSCs）、胃癌组织与癌旁组织间充质干细胞（GCN-MSCs）中差异表达的miRNA，并通过定量RT-PCR方法进行验证。使用集落形成和transwell测定在体外观察GC-MSC对HGC-27细胞的影响，并将这些细胞皮下共注射到小鼠中以评估体内肿瘤生长。结果：miR-214、miR-221和miR-222在GC-MSCs和癌组织中普遍表达上调。其水平与淋巴结转移、静脉浸润及TNM分期密切相关。胃癌组织来源的间充质干细胞通过旁分泌方式显著促进HGC-27的生长和迁移，并增加miR-221的表达，靶向抑制GC-MSCs中的miR-221可阻断其肿瘤支持作用。结论：胃癌组织来源的间充质干细胞通过向胃癌细胞转移exosomal miRNAs促进胃癌的进展，为GC-MSC的作用机制提供了新的思路，并为胃癌的生物学标志物提供了新的参考。
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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影响因子：
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