Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Biochimie. 2019 Feb;157:184-194. doi: 10.1016/j.biochi.2018.11.014. Epub 2018 Nov 24.
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.
长链非编码 RNA(lncRNAs)在各种癌症中经常被涉及。然而,lncRNAs 在鼻咽癌(NPC)中的意义在很大程度上尚不清楚。在这项研究中,我们鉴定了一种新型的 lncRNA 鼻咽癌拷贝数扩增转录本-1(NPCCAT1),其在 NPC 组织中的表达水平高于鼻咽正常组织。此外,我们发现 NPCCAT1 的基因组拷贝数在 NPC 中扩增,这导致了 NPCCAT1 在 NPC 中的上调。功能实验表明,NPCCAT1 的过表达促进 NPC 细胞在体外的生长和迁移以及 NPC 肿瘤在体内的生长。NPCCAT1 的敲低抑制 NPC 细胞的生长和迁移。机制上,我们发现 NPCCAT1 直接结合 YY1 mRNA 5'UTR,促进 YY1 mRNA 的翻译,并上调 YY1 蛋白水平。功能获得和功能丧失实验表明,YY1 促进 NPC 细胞的增殖和迁移。此外,挽救实验表明,YY1 的耗竭减弱了 NPCCAT1 过表达在促进 NPC 细胞在体外的生长和迁移以及 NPC 肿瘤在体内的生长中的作用。总之,我们的研究鉴定了 NPCCAT1 作为一种致癌 lncRNA,通过上调 YY1 促进 NPC 进展,并表明 lncRNA NPCCAT1 可能是 NPC 的一种有前途的治疗靶点。