MicroRNA-506 suppresses tumor proliferation and metastasis in colon cancer by directly targeting the oncogene EZH2

被引:67
作者
Zhang, Yi [1 ,2 ]
Lin, Changwei [3 ]
Liao, Guoqing [1 ]
Liu, Sheng [1 ]
Ding, Jie [4 ]
Tang, Fang [5 ]
Wang, Zhenran [5 ]
Liang, Xingsi [5 ]
Li, Bo [5 ]
Wei, Yangchao [5 ]
Huang, Qi [5 ]
Li, Xuan [5 ]
Tang, Bo [5 ]
机构
[1] Cent S Univ, Xiangya Hosp, Dept Gastrointestinal Surg, Changsha 410008, Hunan, Peoples R China
[2] Xuzhou Med Coll, Dept Surg Oncol, Affiliated Hosp, Xuzhou 221000, Peoples R China
[3] Cent S Univ, Xiangya Hosp 3, Dept Gastrointestinal Surg, Changsha 410008, Hunan, Peoples R China
[4] Guizhou Prov Peoples Hosp, Dept Gastrointestinal Surg, Guiyang 550000, Peoples R China
[5] Guilin Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp, Guilin 541000, Guangxi, Peoples R China
来源
ONCOTARGET | 2015年 / 6卷 / 32期
基金
湖南省自然科学基金; 中国国家自然科学基金;
关键词
miR-506; EZH2; proliferation; metastasis; colon cancer; ZESTE HOMOLOG 2; OVARIAN-CANCER; MESENCHYMAL TRANSITION; CELLS; MIR-506; EXPRESSION; GROWTH; GENE; SIGNATURES; ENHANCER;
D O I
10.18632/oncotarget.5309
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Increasing evidence reveals that aberrant expression of microRNA contributes to the development and progression of colon cancer, but the roles of microRNA-506 (miR-506) in colon cancer remain elusive. Here, we demonstrated that miR-506 was down-regulated in colon cancer tissue and cells and that miR-506 expression was inversely correlated with EZH2 expression, tumor size, lymph node invasion, TNM stage and metastasis. A high level of miR-506 identified patients with a favorable prognosis. In vitro and in vivo experiments confirmed that miR-506 inhibits the proliferation and metastasis of colon cancer, and a luciferase reporter assay confirmed that EZH2 is a direct and functional target of miR-506 via the 3' UTR of EZH2. The restoration of EZH2 expression partially reversed the proliferation and invasion of miR-506-overexpressing colon cancer cells. Moreover, we confirmed that the miR-506-EZH2 axis inhibits proliferation and metastasis by activating/suppressing specific downstream tumor-associated genes and the Wnt/beta-catenin signaling pathway. Taking together, our study sheds light on the role of miR-506 as a suppressor for tumor growth and metastasis and raises the intriguing possibility that miR-506 may serve as a new potential marker for monitoring and treating colon cancer.
引用
收藏
页码:32586 / 32601
页数:16
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