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Long noncoding RNA NPCCAT1 promotes nasopharyngeal carcinoma progression via upregulating YY1

Author:
Su, Hongxia, Liu, Lei, Zhang, Yuan, Wang, Jia, Zhao, Yulin
Source:
Biochimie 2019 v.157 pp. 184-194
ISSN:
0300-9084
Subject:
5' untranslated regions, carcinoma, cell growth, cell proliferation, gain-of-function mutation, gene expression regulation, genomics, loss-of-function mutation, non-coding RNA, protein content, therapeutics, tissues, translation (genetics)
Abstract:
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.
Agid:
6236132