Long and noncoding RNAs (Inc-RNAs) determine androgen receptor dependent gene expression in prostate cancer growth in vivo

• 来源期刊: 亚洲男性学杂志（英文版）
• 年，卷（期）: 2014,（2）
• 页码范围: 268-269
• 页数: 2页
• 语种: 英文
• DOI: 10.4103/1008-682X.122364

摘要

Hyperactive androgen receptor (AR)activity remains a key determinant of the onset and progression of prostate cancer and resistance to current therapies.The mechanisms governing castrate resistant prostate cancer are poorly understood,but defining these molecular events is essential in order to impact deaths from prostate cancer.Yang et al.demonstrate that two lnc-RNAs known to be overexpressed in therapy resistant prostate cancer,PRNCR1 (also known as PCAT8) and PCGEM1,bound to the AR to enhance ligand-dependent and ligand-independent AR gene expression and proliferation of prostate cancer cells.1 The sequence of these interactions involved the binding of PRNCR1 to the acetylated AR and a subsequent association of DOT1L,which was required for the sequential recruitment of the IncRNA PCGEM1 to the AR amino terminus,which in turn was methylated by DOT1L. The AR is a nuclear receptor gene superfamily member that is activated by androgens (5 α-dihydrotestosterone).Ligand-dependent activation of the AR induces cytoplasmic translocation of the receptor to the nucleus and the subsequent formation of multiprotein complexes that coordinates gene expression.The AR is a determinant of reproductive cell function and also governs functions in nonreproductive tissues,including the muscle and brain.The AR undergoes posttranslational modification by phosphorylation,acetylation,and sumoylation.2 The AR binds and is regulated by both histone acetylates (p300,p/CAF) and histone deacetylases.3 AR acetylation3 has been shown to serve as a key node for diverse signaling pathways,including regulation by long noncoding RNAs in the current studies.