Oncotarget

Research Papers:

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

Dong-liang Chen, Dong-sheng Zhang, Yun-xin Lu, Le-zong Chen, Zhao-lei Zeng, Ming-ming He, Feng-hua Wang, Yu-hong Li, Hui-zhong Zhang, Helene Pelicano, Wei Zhang and Rui-hua Xu _

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Oncotarget. 2015; 6:10868-10879. https://doi.org/10.18632/oncotarget.3451

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Abstract

Dong-liang Chen1,2*, Dong-sheng Zhang1,2*, Yun-xin Lu1,2, Le-zong Chen1,2, Zhao-lei Zeng1,3, Ming-ming He1,2, Feng-hua Wang1,2, Yu-hong Li1,2, Hui-zhong Zhang1,4, Helene Pelicano5, Wei Zhang6, Rui-hua Xu1,2

1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

3Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China

4Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China

5Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

6Department of Pathology, Unit 85, Center for RNAi and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, TX, USA

*These authors have contributed equally to this work

Correspondence to:

Rui-hua Xu, e-mail: [email protected]

Keywords: microRNA, microRNA-217, EZH2, gastric cancer, metastasis

Received: January 9, 2015     Accepted: February 25, 2015     Published: March 26, 2015

ABSTRACT

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.


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