Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells
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Wei Wang1,2,5,*, Mei Yi3,*, Shengnan Chen1,2, Junjun Li2, Guo Li4, Jianbo Yang6, Pan Zheng2, Haijing Zhang2, Wei Xiong2, James B. McCarthy6, Guiyuan Li2, Xiaoling Li2, Bo Xiang1,2
1Hunan Provincial Cancer Hospital and Cancer Hospital Affiliated to Xiangya Medical School, The Central South University, Changsha, Hunan 410013, China
2Cancer Research Institute, Xiangya School of Medicine, The Central South University, Changsha 410078, China
3Department of Dermatology, Xiangya Hospital, The Central South University, Changsha, 410008, Hunan, China
4Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, The Central South University, Changsha, 410008, Hunan, China
5Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, China
6Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
*These authors have contributed equally to this work
Bo Xiang, e-mail: email@example.com
Xiaoling Li, e-mail: firstname.lastname@example.org
Keywords: epithelial-mesenchymal transition, nasopharyngeal carcinoma, FOXA1, NOR1
Received: July 02, 2015 Accepted: January 01, 2016 Published: February 27, 2016
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.
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