Ets-1 promoter-associated noncoding RNA regulates the NONO/ERG/Ets-1 axis to drive gastric cancer progression

• Published in: Oncogene Vol. 37; no. 35; pp. 4871 - 4886
• Main Authors: Li, Dan, Chen, Yajun, Mei, Hong, Jiao, Wanju, Song, Huajie, Ye, Lin, Fang, Erhu, Wang, Xiaojing, Yang, Feng, Huang, Kai, Zheng, Liduan, Tong, Qiangsong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2018; Nature Publishing Group
• Subjects: 13/1; 13/109; 13/44; 13/51; 13/89; 14/32; 38/77; 45/90; 631/67/1504/1829; 631/67/395; Amino acids; Antisense RNA; Apoptosis; Cancer; Cancer cells; Cancer metastasis; Cancer research; Care and treatment; Cell Biology; Cellular signal transduction; Development and progression; Electrophoretic mobility; Gastric cancer; Gene expression; Genes; Genetic aspects; Health aspects; Human Genetics; Immunoprecipitation; Internal Medicine; Medicine; Medicine & Public Health; Metastases; Oncogenes; Oncology; Protein binding; Ribonucleic acid; RNA; Stomach cancer; Transcription; Transcription (Genetics); Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-018-0302-4

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.