Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways
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Wei-ming Fu2,*, Ying-fei Lu2,3,*, Bao-guang Hu4, Wei-cheng Liang5, Xiao Zhu6, Hai-di Yang7, Gang Li3,8, Jin-fang Zhang1,3,8
1School of Medicine, South China University of Technology, Guangzhou 511458, P.R. China
2Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, P.R. China
3Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China
4Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China
5School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, P. R. China
6Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Guangdong Medical College, Dong guan, 523808, P.R. China
7Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
8Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, P.R. China
*These authors contributed equally to this work
Jin-fang Zhang, e-mail: [email protected]
Keywords: Hotair, angiogenesis, nasopharyngeal carcinoma, GRP78
Received: July 10, 2015 Accepted: November 25, 2015 Published: December 22, 2015
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.
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