Emerging studies have indicated the essential functions of long noncoding RNAs (lncRNAs) during cancer progression. However, whether lncRNAs contribute to the upregulation of v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), an established oncogenic protein facilitating tumor invasion and metastasis, in gastric cancer remains elusive. Herein, we identified Ets-1 promoter-associated noncoding RNA (pancEts-1) as a novel lncRNA associated with the gastric cancer progression via mining of publicly available datasets and rapid amplification of cDNA ends. RNA pull-down, RNA immunoprecipitation, in vitro binding, and RNA electrophoretic mobility shift assays indicated the binding of pancEts-1 to non-POU domain containing octamer binding (NONO) protein. Mechanistically, pancEts-1 facilitated the physical interaction between NONO and Ets related gene (ERG), resulting in increased ERG transactivation and transcription of Ets-1 associated with gastric cancer progression. In addition, pancEts-1 facilitated the growth and aggressiveness of gastric cancer cells via interacting with NONO. In gastric cancer tissues, pancEts-1, NONO, and ERG were upregulated and significantly correlated with Ets-1 levels. High levels of pancEts-1, NONO, ERG, or Ets-1 were respectively associated with poor survival of gastric cancer patients, whereas simultaneous expression of all of them (HR = 3.012, P = 0.105) was not an independent prognostic factor for predicting clinical outcome. Overall, these results demonstrate that lncRNA pancEts-1 exhibits oncogenic properties that drive the progression of gastric cancer via regulating the NONO/ERG/Ets-1 axis.

中文翻译：

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Ets-1启动子相关的非编码RNA调节NONO / ERG / Ets-1轴以驱动胃癌的进展。

新兴研究表明，在癌症进展过程中长非编码RNA（lncRNA）的基本功能。然而，lncRNAs是否有助于上调v-ets成红细胞病病毒E26癌基因同源物1（Ets-1），一种已经建立的致癌蛋白，促进肿瘤的侵袭和转移，目前尚不清楚。本文中，我们通过挖掘可公开获得的数据集和快速扩增cDNA末端，将Ets-1启动子相关的非编码RNA（pancEts-1）确定为与胃癌进展相关的新型lncRNA。RNA下拉，RNA免疫沉淀，体外结合和RNA电泳迁移率变动分析表明pancEts-1与非POU域包含八聚体结合（NONO）蛋白的结合。机械上，pancEts-1促进了NONO与Ets相关基因（ERG）之间的物理相互作用，导致与胃癌进展相关的ERG-1转录激活和Ets-1转录增加。此外，pancEts-1通过与NONO相互作用促进了胃癌细胞的生长和侵袭性。在胃癌组织中，pancEts-1，NONO和ERG上调，并与Ets-1水平显着相关。pancEts-1，NONO，ERG或Ets-1的高水平分别与胃癌患者的不良生存相关，而所有这些基因的同时表达（HR = 3.012，P = 0.105）不是预测的独立预后因素。临床结果。全面的，