Long noncoding RNA hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways

Abstract

// Wei-ming Fu 2, * , Ying-fei Lu 2, 3, * , Bao-guang Hu 4 , Wei-cheng Liang 5 , Xiao Zhu 6 , Hai-di Yang 7 , Gang Li 3, 8 , Jin-fang Zhang 1, 3, 8 1 School of Medicine, South China University of Technology, Guangzhou 511458, P.R. China 2 Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, P.R. China 3 Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China 4 Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China 5 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, P. R. China 6 Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Guangdong Medical College, Dong guan, 523808, P.R. China 7 Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China 8 Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, P.R. China * These authors contributed equally to this work Correspondence to: Jin-fang Zhang, e-mail: zhangjf06@cuhk.edu.hk Keywords: Hotair, angiogenesis, nasopharyngeal carcinoma, GRP78 Received: July 10, 2015      Accepted: November 25, 2015      Published: December 22, 2015 ABSTRACT Nasopharyngeal carcinoma (NPC), as a unique head and neck cancer type, is particularly prevalent in certain geographic areas such as eastern Asia. Until now, the therapeutic options have been restricted mainly to radiotherapy or chemotherapy. However, the clinical treatment effect remains unsatisfactory even if the combined radio-chemotherapies. Therefore, it is urgently needed to develop effective novel therapies against NPC. In this study, we discovered that lncRNA Hotair was extremely abundant in NPC cells and clinical NPC samples. Further studies showed that Hotair knockdown significantly attenuated both in vitro and in vivo tumor cell growth and angiogenesis. Our study also demonstrated that Hotair promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as through GRP78-mediated upregulation of VEGFA and Ang2 expression. Therefore, Hotair may serve as a promising diagnostic marker and therapeutic target for NPC patients.