Fu Wei-Ming, Lu Ying-Fei, Hu Bao-Guang, Liang Wei-Cheng, Zhu Xiao, Yang Hai-di, Li Gang, Zhang Jin-Fang
Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, P.R. China.
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China.
Oncotarget. 2016 Jan 26;7(4):4712-23. doi: 10.18632/oncotarget.6731.
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.
鼻咽癌(NPC)作为一种独特的头颈癌类型,在东亚等某些地理区域尤为普遍。到目前为止,治疗选择主要限于放疗或化疗。然而,即使采用联合放化疗,临床治疗效果仍不尽人意。因此,迫切需要开发针对鼻咽癌的有效新疗法。在本研究中,我们发现lncRNA Hotair在NPC细胞和临床NPC样本中极其丰富。进一步研究表明,敲低Hotair可显著减弱体外和体内肿瘤细胞的生长及血管生成。我们的研究还表明,Hotair通过直接激活血管生成因子VEGFA的转录以及通过GRP78介导的VEGFA和Ang2表达上调来促进血管生成。因此,Hotair可能成为鼻咽癌患者有前景的诊断标志物和治疗靶点。