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

TitleThe oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.
Publication TypeJournal Article
Year of Publication2014
AuthorsChakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, Mosquera JMiguel, Pauwels J, Park K, Kossai M, MacDonald TY, Fontugne J, Erho N, Vergara IA, Ghadessi M, Davicioni E, Jenkins RB, Palanisamy N, Chen Z, Nakagawa S, Hirose T, Bander NH, Beltran H, Fox AH, Elemento O, Rubin MA
JournalNat Commun
Date Published2014 Nov 21
KeywordsAdenocarcinoma, Cell Line, Tumor, Chromatin Immunoprecipitation, Disease Progression, Epigenesis, Genetic, Estrogen Receptor alpha, Humans, Male, Prostatic Neoplasms, RNA, Long Noncoding, Sequence Analysis, RNA

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.

Alternate JournalNat Commun
PubMed ID25415230
PubMed Central IDPMC4241506
Grant ListR01 CA152057 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UL1TR000457 / TR / NCATS NIH HHS / United States