Long noncoding RNAs (lncRNAs) are frequently implicated in various cancers. However, the significances of lncRNAs in nasopharyngeal carcinoma (NPC) are largely unclear. In this study, we identified a novel lncRNA nasopharyngeal carcinoma copy number amplified transcript-1 (NPCCAT1), whose expression is increased in NPC tissues compared with nasopharyngeal normal tissues. Furthermore, we found the genomic copy number of NPCCAT1 is amplified in NPC, which contributes to the upregulation of NPCCAT1 in NPC. Functional experiments demonstrated that overexpression of NPCCAT1 promotes NPC cell growth and migration in vitro and NPC tumor growth in vivo. Knockdown of NPCCAT1 suppresses NPC cell grow and migration. Mechanistically, we found that NPCCAT1 directly binds YY1 mRNA 5′UTR, promotes YY1 mRNA translation, and upregulates YY1 protein level. Gain-of-function and loss-of-function assays revealed that YY1 promoted NPC cell proliferation and migration. Moreover, rescue assays showed that depletion of YY1 attenuated the roles of NPCCAT1 overexpression in promoting NPC cell growth and migration in vitro and NPC tumor growth in vivo. Overall, our study identified NPCCAT1 as an oncogenic lncRNA which promotes NPC progression via upregulating YY1, and suggested that lncRNA NPCCAT1 may be a promising therapeutic target for NPC.

长的非编码RNA（lncRNA）经常与各种癌症有关。但是，lncRNA在鼻咽癌（NPC）中的意义尚不清楚。在这项研究中，我们确定了一种新型的lncRNA鼻咽癌拷贝数扩增转录本1（NPCCAT1），其在鼻咽癌组织中的表达与鼻咽正常组织相比有所增加。此外，我们发现NPCCAT1的基因组拷贝数在NPC中得到了扩增，这有助于NPCCAT1在NPC中的上调。功能实验表明，NPCCAT1的过表达促进体外NPC细胞的生长和迁移以及体内NPC肿瘤的生长。敲低NPCCAT1可抑制NPC细胞的生长和迁移。从机理上讲，我们发现NPCCAT1直接与YY1 mRNA 5'UTR结合，促进YY1 mRNA的翻译，并上调YY1蛋白的水平。功能获得和功能丧失测定显示YY1促进NPC细胞增殖和迁移。此外，营救试验显示，YY1的耗竭减弱了NPCCAT1过表达在促进NPC细胞体外生长和迁移以及体内NPC肿瘤生长中的作用。总体而言，我们的研究确定NPCCAT1为通过上调YY1促进NPC进展的致癌lncRNA，并暗示lncRNA NPCCAT1可能是NPC的有希望的治疗靶标。