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Nat Commun. 2014 Nov 21;5:5383. doi: 10.1038/ncomms6383.

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

Author information

1
1] Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA [2] Institute for Precision Medicine, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York 10021, USA.
2
1] Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA [2] Institute for Precision Medicine, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York 10021, USA [3] Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.
3
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington DC 20037, USA.
4
1] Biological Sciences Department, New York City College of Technology, City University of New York, Brooklyn, New York 11201, USA [2] Arthritis and Tissue Degeneration Program and the David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, New York 10021, USA.
5
School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
6
Chemical Genomics Centre, 44227 Dortmund, Germany.
7
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA.
8
Research and Development, GenomeDx Biosciences, Vancouver, British Columbia, Canada V6B 1B8.
9
Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
10
1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48105, USA [2] Henry Ford Health System, Medical Group Urology - Prostate Cancer Research, 1 Ford Place, Room 2D26, Detroit, Michigan 48202, USA.
11
Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, New York 10021, USA.
12
RNA Biology Laboratory, RIKEN Advanced Research Institute, Hirosawa 2-1, Wako 351-0198, Japan.
13
Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
14
Department of Urology, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.
15
1] Institute for Precision Medicine, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York 10021, USA [2] Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.

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.

PMID:
25415230
PMCID:
PMC4241506
DOI:
10.1038/ncomms6383
[Indexed for MEDLINE]
Free PMC Article

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