雌激素受体α调控的长链非编码RNA NEAT1是前列腺癌的关键调节因子。
The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.
作者信息
Chakravarty Dimple, Sboner Andrea, Nair Sujit S, Giannopoulou Eugenia, Li Ruohan, Hennig Sven, Mosquera Juan Miguel, Pauwels Jonathan, Park Kyung, Kossai Myriam, MacDonald Theresa Y, Fontugne Jacqueline, Erho Nicholas, Vergara Ismael A, Ghadessi Mercedeh, Davicioni Elai, Jenkins Robert B, Palanisamy Nallasivam, Chen Zhengming, Nakagawa Shinichi, Hirose Tetsuro, Bander Neil H, Beltran Himisha, Fox Archa H, Elemento Olivier, Rubin Mark A
机构信息
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.
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.
出版信息
Nat Commun. 2014 Nov 21;5:5383. doi: 10.1038/ncomms6383.
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.
雄激素受体（AR）在建立驱动前列腺癌进展的致癌级联反应中起核心作用。一些前列腺癌逃避雄激素依赖，且常与侵袭性表型相关。雌激素受体α（ERα）在前列腺癌中表达，与AR状态无关。然而，ERα的作用仍不明确。通过结合染色质免疫沉淀（ChIP）和RNA测序数据，我们鉴定出一种ERα特异性非编码转录组特征。在推测由ERα调控的基因间长链非编码RNA（lncRNA）中，我们确定核富集丰富转录本1（NEAT1）是前列腺癌中表达最显著上调的lncRNA。对两个大型临床队列的分析还表明，NEAT1表达与前列腺癌进展相关。表达高水平NEAT1的前列腺癌细胞对雄激素或AR拮抗剂具有抗性。最后，我们提供证据表明，NEAT1通过改变靶基因启动子的表观遗传景观以促进转录来驱动致癌生长。
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