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

Dimple Chakravarty, Andrea Sboner, Sujit S. Nair, Eugenia Giannopoulou, Ruohan Li, Sven Hennig, Juan Miguel Mosquera, Jonathan Pauwels, Kyung Park, Myriam Kossai, Theresa Y. MacDonald, Jacqueline Fontugne, Nicholas Erho, Ismael A. Vergara, Mercedeh Ghadessi, Elai Davicioni, Robert B. Jenkins, Nallasivam Palanisamy, Zhengming Chen, Shinichi Nakagawa, Tetsuro Hirose, Neil H. Bander, Himisha Beltran, Archa H. Fox, Olivier Elemento and Mark A. Rubin ()
Additional contact information
Dimple Chakravarty: Weill Medical College of Cornell University
Andrea Sboner: Weill Medical College of Cornell University
Sujit S. Nair: School of Medicine and Health Sciences, George Washington University
Eugenia Giannopoulou: New York City College of Technology, City University of New York
Ruohan Li: School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia
Sven Hennig: Chemical Genomics Centre
Juan Miguel Mosquera: Weill Medical College of Cornell University
Jonathan Pauwels: Weill Medical College of Cornell University
Kyung Park: Weill Medical College of Cornell University
Myriam Kossai: Weill Medical College of Cornell University
Theresa Y. MacDonald: Weill Medical College of Cornell University
Jacqueline Fontugne: Weill Medical College of Cornell University
Nicholas Erho: Research and Development, GenomeDx Biosciences
Ismael A. Vergara: Research and Development, GenomeDx Biosciences
Mercedeh Ghadessi: Research and Development, GenomeDx Biosciences
Elai Davicioni: Research and Development, GenomeDx Biosciences
Robert B. Jenkins: Mayo Clinic
Nallasivam Palanisamy: Michigan Center for Translational Pathology, University of Michigan
Zhengming Chen: Weill Cornell Medical College
Shinichi Nakagawa: RNA Biology Laboratory, RIKEN Advanced Research Institute
Tetsuro Hirose: Institute for Genetic Medicine, Hokkaido University
Neil H. Bander: Weill Cornell Medical College of Cornell University
Himisha Beltran: Weill Medical College of Cornell University
Archa H. Fox: School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia
Olivier Elemento: Institute for Precision Medicine, Weill Medical College of Cornell University and New York Presbyterian Hospital
Mark A. Rubin: Weill Medical College of Cornell University

Nature Communications, 2014, vol. 5, issue 1, 1-16

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6383

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