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分析雄激素受体调控的长链非编码 RNA 图谱,鉴定出 ARLNC1 在前列腺癌进展中的作用。

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.

机构信息

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

出版信息

Nat Genet. 2018 Jun;50(6):814-824. doi: 10.1038/s41588-018-0120-1. Epub 2018 May 28.

Abstract

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

摘要

雄激素受体 (AR) 在正常前列腺和前列腺癌的发展中起着关键作用。通过对前列腺癌细胞系和组织的综合转录组分析,我们发现 ARLNC1(AR 调节的长非编码 RNA 1)是一种重要的长非编码 RNA,与前列腺癌进展中的 AR 信号密切相关。ARLNC1 不仅受 AR 蛋白诱导,还通过 RNA-RNA 相互作用稳定 AR 转录本。ARLNC1 敲低抑制了 AR 表达、全局 AR 信号和前列腺癌在体外和体内的生长。总之,这些数据支持 ARLNC1 在维持正向反馈环中发挥作用,该反馈环在前列腺癌进展过程中增强 AR 信号,并将 ARLNC1 鉴定为一种新的治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ece4/5980762/442bdb1581e5/nihms954411f1.jpg

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