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; Mark A. Rubin

doi:10.1038/ncomms6383

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 NakagawaTetsuro Hirose, Neil H. Bander, Himisha Beltran, Archa H. Fox, Olivier Elemento, Mark A. Rubin

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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.

Original language	English (US)
Article number	5383
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6383
State	Published - 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Chakravarty, D., Sboner, A., Nair, S. S., Giannopoulou, E., Li, R., Hennig, S., Mosquera, J. M., Pauwels, J., Park, K., Kossai, M., Macdonald, T. Y., Fontugne, J., Erho, N., Vergara, I. A., Ghadessi, M., Davicioni, E., Jenkins, R. B., Palanisamy, N., Chen, Z., ... Rubin, M. A. (2014). The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nature communications, 5, Article 5383. https://doi.org/10.1038/ncomms6383

Chakravarty, D, Sboner, A, Nair, SS, Giannopoulou, E, Li, R, Hennig, S, Mosquera, JM, 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 2014, 'The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer', Nature communications, vol. 5, 5383. https://doi.org/10.1038/ncomms6383

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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.",

author = "Dimple Chakravarty and Andrea Sboner and Nair, {Sujit S.} and Eugenia Giannopoulou and Ruohan Li and Sven Hennig and Mosquera, {Juan Miguel} and Jonathan Pauwels and Kyung Park and Myriam Kossai and Macdonald, {Theresa Y.} and Jacqueline Fontugne and Nicholas Erho and Vergara, {Ismael A.} and Mercedeh Ghadessi and Elai Davicioni and Jenkins, {Robert B.} and Nallasivam Palanisamy and Zhengming Chen and Shinichi Nakagawa and Tetsuro Hirose and Bander, {Neil H.} and Himisha Beltran and Fox, {Archa H.} and Olivier Elemento and Rubin, {Mark A.}",

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T1 - The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

AU - Chakravarty, Dimple

AU - Sboner, Andrea

AU - Nair, Sujit S.

AU - Giannopoulou, Eugenia

AU - Li, Ruohan

AU - Hennig, Sven

AU - Mosquera, Juan Miguel

AU - Pauwels, Jonathan

AU - Park, Kyung

AU - Kossai, Myriam

AU - Macdonald, Theresa Y.

AU - Fontugne, Jacqueline

AU - Erho, Nicholas

AU - Vergara, Ismael A.

AU - Ghadessi, Mercedeh

AU - Davicioni, Elai

AU - Jenkins, Robert B.

AU - Palanisamy, Nallasivam

AU - Chen, Zhengming

AU - Nakagawa, Shinichi

AU - Hirose, Tetsuro

AU - Bander, Neil H.

AU - Beltran, Himisha

AU - Fox, Archa H.

AU - Elemento, Olivier

AU - Rubin, Mark A.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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

Abstract

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