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Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

2014; National Academy of Sciences; Volume: 111; Issue: 20 Linguagem: Inglês

10.1073/pnas.1324151111

1091-6490

Chen-Lin Hsieh, Fei Teng, Yiwen Chen, Tiantian Li, Yanfei Gao, Xiaodong Wang, Tong Sun, Christopher J. Sweeney, Gwo‐Shu Mary Lee, Shaoyong Chen, Steven P. Balk, Xiaole Shirley Liu, Myles Brown, Philip W. Kantoff,

Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Significance We report that enhancer RNAs (eRNAs), a class of long noncoding RNAs, participate in the androgen receptor (AR)-dependent looping complex that enhances spatial communication of distal enhancers and target promoters, leading to transcriptional activation events. Furthermore, our data show that KLK3 eRNA (KLK3e) selectively enhances the gene expression of AR-regulated genes, and provide evidence for a positive regulatory loop in which AR-dependent transcription is modulated by an intermediate eRNA. These findings may translate into improved RNA-based therapy (eRNA suppression) to enhance the durability of androgen deprivation therapy (ADT) and prediction of the efficacy of ADT by measuring the enhancer-derived activity (eRNA expression) in prostate tumors.