Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells.

// Wei Wang 1, 2, 5, * , Mei Yi 3, * , Shengnan Chen 1, 2 , Junjun Li 2 , Guo Li 4 , Jianbo Yang 6 , Pan Zheng 2 , Haijing Zhang 2 , Wei Xiong 2 , James B. McCarthy 6 , Guiyuan Li 2 , Xiaoling Li 2 , Bo Xiang 1, 2 1 Hunan Provincial Cancer Hospital and Cancer Hospital Affiliated to Xiangya Medical School, The Central South University, Changsha, Hunan 410013, China 2 Cancer Research Institute, Xiangya School of Medicine, The Central South University, Changsha 410078, China 3 Department of Dermatology, Xiangya Hospital, The Central South University, Changsha, 410008, Hunan, China 4 Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, The Central South University, Changsha, 410008, Hunan, China 5 Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, China 6 Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA * These authors have contributed equally to this work Correspondence to: Bo Xiang, e-mail: xiangbolin@csu.edu.cn Xiaoling Li, e-mail: lixiaoling@csu.edu.cn Keywords: epithelial-mesenchymal transition, nasopharyngeal carcinoma, FOXA1, NOR1 Received: July 02, 2015      Accepted: January 01, 2016      Published: February 27, 2016 ABSTRACT The epithelial-mesenchymal transition (EMT) process is believed to play a crucial role in nasopharyngeal carcinoma (NPC) progression, a squamous cell carcinoma of the head and neck with the tendency to metastasize early. At present, much attention has been given to the inducer of EMT involved in NPC progression, while antagonists have been less intensively characterized. In this study, unbiased analysis of EMT-associated gene expression patterns was performed using data mining of global gene expression profiles derived from NPC samples, leading to the successful identification of NOR1, FOXA1, and Slug, all of which showed aberrant expression during NPC progression. The effect of tumor suppressor NOR1 on Slug-induced NPC cells during the EMT process was investigated by use of ectopic expression and RNA interference methods. The molecular mechanisms underlying the tumor-suppressing effect of NOR1 on Slug-induced EMT were thought to be dependent on the cooperation of NOR1 with the FOXA1-HDAC2 complex. We also showed that FOXA1 and HDAC2 bind the slug promoter and directly repress its transcription. Our data revealed a previously unrecognized role of the NOR1-FOXA1/HDAC2-Slug network in the regulation of the EMT process and aggressiveness of NPC.