microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer

被引:68
|
作者
Chen, Dong-liang [1 ,2 ]
Zhang, Dong-sheng [1 ,2 ]
Lu, Yun-xin [1 ,2 ]
Chen, Le-zong [1 ,2 ]
Zeng, Zhao-lei [1 ,3 ]
He, Ming-ming [1 ,2 ]
Wang, Feng-hua [1 ,2 ]
Li, Yu-hong [1 ,2 ]
Zhang, Hui-zhong [1 ,4 ]
Pelicano, Helene [5 ]
Zhang, Wei [6 ]
Xu, Rui-hua [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510275, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Ctr Canc, Dept Pathol, Guangzhou 510275, Guangdong, Peoples R China
[5] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
[6] Univ Texas MD Anderson Canc Ctr, Ctr RNAi & Noncoding RNA, Unit 85, Dept Pathol, Houston, TX 77030 USA
基金
中国国家自然科学基金; 国家高技术研究发展计划(863计划);
关键词
microRNA; microRNA-217; EZH2; gastric cancer; metastasis; PANCREATIC DUCTAL ADENOCARCINOMA; CELL-PROLIFERATION; EXPRESSION; POLYCOMB; GLIOBLASTOMA; MIGRATION; OVEREXPRESSION; CARCINOMA; SURVIVAL; INVASION;
D O I
10.18632/oncotarget.3451
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
microRNA-217 (miR-217) is frequently dysregulated in cancer. Here, we report that miR-217 levels were lower in tumor tissue compared with the adjacent normal tissue. Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased cell proliferation and invasion. Further experiments revealed that Polycomb group protein enhancer of zeste homolog 2 (EZH2) was a direct target of miR-217 in gastric cancer cells. Knockdown of EZH2 mimicked the tumor-suppressive effects of miR-217 in gastric cancer cells, whereas the reintroduction of EZH2 abolished its effects. Taken together, these results demonstrated that miR-217 may be used as a prognostic marker, and the newly identified miR-217-EZH2 axis may be a potential target in the development of therapeutic strategies for gastric cancer patients.
引用
收藏
页码:10868 / 10879
页数:12
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