title: The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.
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.
authors.affiliation: 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.
authors.forename: Dimple
authors.initials: D
authors.lastname: Chakravarty
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington DC 20037, USA.
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Nair
authors.affiliation: 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.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Giannopoulou
authors.affiliation: School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
authors.forename: Ruohan
authors.initials: R
authors.lastname: Li
authors.affiliation: Chemical Genomics Centre, 44227 Dortmund, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hennig
authors.affiliation: 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.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pauwels
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA.
authors.forename: Kyung
authors.initials: K
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Myriam
authors.initials: M
authors.lastname: Kossai
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA.
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.affiliation: 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.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fontugne
authors.affiliation: Research and Development, GenomeDx Biosciences, Vancouver, British Columbia, Canada V6B 1B8.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.affiliation: Research and Development, GenomeDx Biosciences, Vancouver, British Columbia, Canada V6B 1B8.
authors.forename: Ismael A
authors.initials: IA
authors.lastname: Vergara
authors.affiliation: Research and Development, GenomeDx Biosciences, Vancouver, British Columbia, Canada V6B 1B8.
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Ghadessi
authors.affiliation: Research and Development, GenomeDx Biosciences, Vancouver, British Columbia, Canada V6B 1B8.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: 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.
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, New York 10021, USA.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Chen
authors.affiliation: RNA Biology Laboratory, RIKEN Advanced Research Institute, Hirosawa 2-1, Wako 351-0198, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Department of Urology, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.affiliation: 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.
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.affiliation: School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
authors.forename: Archa H
authors.initials: AH
authors.lastname: Fox
authors.affiliation: 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.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: 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.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C577276:NEAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding