Zhang Ziping, Liu Shaoqun, Shi Rongliang, Zhao Guangfa
General Surgery, Central Hospital of Shanghai Minhang District, China.
Cancer Genet. 2011 Sep;204(9):486-91. doi: 10.1016/j.cancergen.2011.07.004.
microRNAs (miRNAs) play an important role in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In the current study, we defined the target genes and biological functions of miR-27 with a luciferase reporter assay and Western blot analysis. We verified that miR-27 levels were increased in gastric cancer tissues. The overexpression of miR-27 promoted the metastasis of AGS cells, whereas its depletion decreased cell metastasis. Up-regulation of miR-27 increased the levels of the epithelial-mesenchymal transition (EMT)-associated genes ZEB1, ZEB2, Slug, and Vimentin, as well as decreased E-cadherin levels. We demonstrated that miR-27 promoted EMT by activating the Wnt pathway. Finally, the APC gene was identified as the direct and functional target of miR-27. These results suggest an important role of miR-27 in regulating metastasis of gastric cancer and implicate the potential application of miR-27 in gastric cancer therapy.
微小RNA（miRNA）在肿瘤发生过程中发挥着重要作用。然而，miRNA调控胃癌转移的机制仍知之甚少。在本研究中，我们通过荧光素酶报告基因检测和蛋白质印迹分析确定了miR-27的靶基因和生物学功能。我们证实，胃癌组织中miR-27水平升高。miR-27的过表达促进了AGS细胞的转移，而其表达缺失则降低了细胞转移。miR-27的上调增加了上皮-间质转化（EMT）相关基因ZEB1、ZEB2、Slug和波形蛋白的水平，同时降低了E-钙黏蛋白水平。我们证明miR-27通过激活Wnt信号通路促进EMT。最后，APC基因被确定为miR-27的直接功能性靶标。这些结果表明miR-27在调控胃癌转移中具有重要作用，并提示miR-27在胃癌治疗中的潜在应用价值。
