Long noncoding RNA XIST promotes malignancies of esophageal squamous cell carcinoma via regulation of miR-101/EZH2

// Xiaoliang Wu 1, 2, * , Xiaoxiao Dinglin 3, * , Xing Wang 2, * , Wen Luo 1 , Qi Shen 1 , Yong Li 1 , Ling Gu 2, 4 , Qianghua Zhou 2 , Haotu Zhu 2 , Yanjie Li 5 , Chaodi Tan 6 , Xianzi Yang 7 and Zhenfeng Zhang 8, 2 1 Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang, China 2 State Key Laboratory of Oncology in South China & Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China 3 Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 4 Puer University, Puer, China 5 The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 6 Sun Yat-sen University, Guangzhou, China 7 Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China 8 Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Zhenfeng Zhang, email: zhangzhf@gzhmu.edu.cn Xianzi Yang, email: yangxz@mail2.sysu.edu.cn Keywords: long non-coding RNA, XIST, EZH2, esophageal squamous cell carcinoma, EMT Received: March 08, 2017      Accepted: May 22, 2017      Published: June 27, 2017 ABSTRACT The long non-coding RNA XIST is a long non-coding RNA that associates with polycomb repressive complex 2 to regulate X-chromosome inactivation in female mammals. The biological roles as well as the underlying mechanisms of XIST in esophageal squamous cell carcinoma remained yet to be solved. Our data indicated that XIST was significantly upregulated in esophageal squamous cancerous tissues and cancer cell lines, as compared with that in the corresponding non-cancerous tissues and immortalized normal squamous epithelial cells. High XIST expression predicted poor prognosis of esophageal squamous cancer patients. Lentivirus mediated knockdown of XIST inhibited proliferation, migration and invasion of esophageal squamous cancer cells in vitro and suppressed tumor growth in vivo . Knockdown of XIST resulted in elevated expression of miR-101 and decreased expression of EZH2. Further analysis showed that XIST functioned as the competitive endogenous RNA of miR-101 to regulate EZH2 expression. Moreover, enforced expression of EZH2 significantly attenuated the anti-proliferation activity upon XIST knockdown. Conclusively, XIST plays an important role in malignant progression of ESCC via modulation of miR-101/EZH2 axis.