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长链非编码RNA NEAT1通过稳定ELF3信使核糖核酸促进胰腺癌的生长和转移。

LncRNA NEAT1 facilitates pancreatic cancer growth and metastasis through stabilizing ELF3 mRNA.

作者信息

Feng Yaguang, Gao Ling, Cui Guangfei, Cao Yan

机构信息

Department of Gastrointestinal and Hepatobiliary Surgery, The First People's Hospital of Shangqiu Shangqiu 476000, Henan Province, China.

出版信息

Am J Cancer Res. 2020 Jan 1;10(1):237-248. eCollection 2020.

Abstract

Recently, increasing evidence has revealed that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of multiple cancers. Although the oncogenic effects of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in some cancers have been reported, the functional significance and molecular mechanism of NEAT1 in pancreatic cancer (PC) progression remains elusive. In this study, our findings showed that NEAT1 expression was upregulated in PC tissues and cell lines; high NEAT1 expression was associated with tumor size, TNM stage, lymph node and distant metastasis, and also predicted poor prognosis. Functional experiments demonstrated that NEAT1 could promote PC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NEAT1 could associate with E74 like ETS transcription factor 3 (ELF3) mRNA and enhance the combination of Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and ELF3 mRNA, subsequently suppressing the degradation of ELF3 mRNA. Overall, our research indicates that NEAT1 might be a potential therapeutic target for patients with PC.

摘要

最近,越来越多的证据表明,长链非编码RNA(lncRNAs)在多种癌症的发病机制中发挥着重要作用。尽管lncRNA富核丰富转录本1(NEAT1)在某些癌症中的致癌作用已有报道,但NEAT1在胰腺癌(PC)进展中的功能意义和分子机制仍不清楚。在本研究中,我们的研究结果表明,NEAT1在PC组织和细胞系中表达上调;NEAT1高表达与肿瘤大小、TNM分期、淋巴结和远处转移相关,并且还预示着预后不良。功能实验表明,NEAT1在体外和体内均可促进PC细胞增殖和转移。机制上,NEAT1可与E74样ETS转录因子3(ELF3)mRNA结合,并增强胰岛素样生长因子2 mRNA结合蛋白1(IGF2BP1)与ELF3 mRNA的结合,随后抑制ELF3 mRNA的降解。总体而言,我们的研究表明,NEAT1可能是PC患者的潜在治疗靶点。

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