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

Overview

abstract

  • 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.

publication date

  • November 21, 2014

Research

keywords

  • Adenocarcinoma
  • Epigenesis, Genetic
  • Estrogen Receptor alpha
  • Prostatic Neoplasms
  • RNA, Long Noncoding

Identity

PubMed Central ID

  • PMC4241506

Scopus Document Identifier

  • 84923284989

Digital Object Identifier (DOI)

  • 10.1038/ncomms6383

PubMed ID

  • 25415230

Additional Document Info

volume

  • 5