The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

• Published in: Nature communications 2014-11, Vol.5 (1), p.5383-5383, Article 5383
• Main Authors: Chakravarty, Dimple, Sboner, Andrea, Nair, Sujit S., Giannopoulou, Eugenia, Li, Ruohan, Hennig, Sven, Mosquera, Juan Miguel, Pauwels, Jonathan, Park, Kyung, Kossai, Myriam, MacDonald, Theresa Y., Fontugne, Jacqueline, Erho, Nicholas, Vergara, Ismael A., Ghadessi, Mercedeh, Davicioni, Elai, Jenkins, Robert B., Palanisamy, Nallasivam, Chen, Zhengming, Nakagawa, Shinichi, Hirose, Tetsuro, Bander, Neil H., Beltran, Himisha, Fox, Archa H., Elemento, Olivier, Rubin, Mark A.
• Format: Article
• Language: English
• Subjects: 13/109; 13/89; 14/32; 38/77; 38/91; 59/5; 631/67/589/466; 631/80/86; 64/60; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Cell Line, Tumor; Chromatin Immunoprecipitation; Disease Progression; Epigenesis, Genetic; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Humanities and Social Sciences; Humans; Male; multidisciplinary; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Science; Science (multidisciplinary); Sequence Analysis, RNA
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6383

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription. While prostate cancer predominantly exhibits androgen dependence, oestrogen receptor (ER) signalling is also involved. Here, Chakravarty et al. show that ERα regulates the expression of the NEAT1 long non-coding RNA, which in turn promotes tumorigenesis by maintaining an oncogenic programme/cascade.