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

// Dong-liang Chen 1, 2 * , Dong-sheng Zhang 1, 2 * , Yun-xin Lu 1, 2 , Le-zong Chen 1, 2 , Zhao-lei Zeng 1, 3 , Ming-ming He 1, 2 , Feng-hua Wang 1, 2 , Yu-hong Li 1, 2 , Hui-zhong Zhang 1, 4 , Helene Pelicano 5 , Wei Zhang 6 , Rui-hua Xu 1, 2 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China 2 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China 3 Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China 4 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China 5 Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Department 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: xurh@sysucc.org.cn 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.