幾個(gè)“長的非編碼RNAs”(lncRNAs) 已知在前列腺癌中過度表達(dá),。Michael Rosenfeld及同事研究了這些“長的非編碼RNAs”中的兩個(gè)的機(jī)制功能和生物功能，它們分別是PRNCR1 和 PCGEM1,。二者都被發(fā)現(xiàn)依賴于特定的翻譯后修飾與雄性激素受體(AR)發(fā)生相互作用,，增強(qiáng)與AR結(jié)合在一起的增強(qiáng)子向目標(biāo)基因啟動(dòng)子的成環(huán)作用(looping),，導(dǎo)致基因表達(dá)增強(qiáng)。它們還增強(qiáng)前列腺癌細(xì)胞由AR-介導(dǎo)的增殖,，并且是一個(gè)前列腺癌異種移植小鼠模型的腫瘤生長所需要的,。PRNCR1 和 PCGEM1在“去勢抵抗性前列腺癌”細(xì)胞系中被上調(diào)。這篇文章中所揭示的lncRNAs在前列腺癌中的調(diào)控作用也許能為新的治療方法開辟道路,。（生物谷 Bioon.com）

生物谷推薦的英文摘要

Nature  doi:10.1038/nature12451

lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs

Liuqing Yang,  Chunru Lin,  Chunyu Jin,  Joy C. Yang,  Bogdan Tanasa,  Wenbo Li,  Daria Merkurjev,  Kenneth A. Ohgi,  Da Meng,  Jie Zhang,  Christopher P. Evans  & Michael G. Rosenfeld

Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis1, their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells2, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy3. Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated androgen receptor on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the androgen receptor amino terminus that is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus 2 PHD domain enhances selective looping of androgen-receptor-bound enhancers to target gene promoters in these cells. In ‘resistant’ prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length androgen receptor, causing ligand-independent activation of the androgen receptor transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumour xenograft growth in vivo. Together, these results indicate that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumours.