miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition

被引:268
作者
Zhang, Ziping [2 ]
Liu, Shaoqun [2 ]
Shi, Rongliang [2 ]
Zhao, Guangfa [1 ]
机构
[1] Shanghai Canc Hosp, Shanghai, Peoples R China
[2] Cent Hosp Shanghai Minhang Dist, Shanghai, Peoples R China
关键词
Gastric cancer; miR-27; EMT; metastasis; BETA-CATENIN; BREAST-CANCER; EXPRESSION; MICRORNAS; PATHWAY; LOOP;
D O I
10.1016/j.cancergen.2011.07.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:486 / 491
页数:6
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