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非编码 RNA 与雄激素受体的相互作用及其在前列腺癌中的特殊作用。

Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer.

机构信息

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1983535511, Iran.

Institute of Human Genetics, Jena University Hospital, 07747 Jena, Germany.

出版信息

Cells. 2021 Nov 16;10(11):3198. doi: 10.3390/cells10113198.

Abstract

The androgen receptor (AR) is a member of the nuclear receptor superfamily and has three functional domains, namely the N-terminal, DNA binding, and C-terminal domain. The N-terminal domain harbors potent transactivation functions, whereas the C-terminal domain binds to androgens and antiandrogens used to treat prostate cancer. AR has genomic activity being DNA binding-dependent or through interaction with other DNA-bound transcription factors, as well as a number of non-genomic, non-canonical functions, such as the activation of the ERK, AKT, and MAPK pathways. A bulk of evidence indicates that non-coding RNAs have functional interactions with AR. This type of interaction is implicated in the pathogenesis of human malignancies, particularly prostate cancer. In the current review, we summarize the available data on the role of microRNAs, long non-coding RNAs, and circular RNAs on the expression of AR and modulation of AR signaling, as well as the effects of AR on their expression. Recognition of the complicated interaction between non-coding RNAs and AR has practical importance in the design of novel treatment options, as well as modulation of response to conventional therapeutics.

摘要

雄激素受体 (AR) 是核受体超家族的成员,具有三个功能域,即 N 端、DNA 结合和 C 端结构域。N 端结构域具有强大的转录激活功能,而 C 端结构域与用于治疗前列腺癌的雄激素和抗雄激素结合。AR 具有基因组活性,这依赖于 DNA 结合或与其他 DNA 结合转录因子的相互作用,以及许多非基因组、非规范的功能,如 ERK、AKT 和 MAPK 途径的激活。大量证据表明,非编码 RNA 与 AR 具有功能相互作用。这种相互作用与人类恶性肿瘤的发病机制有关,特别是前列腺癌。在本综述中,我们总结了关于 microRNAs、长非编码 RNA 和环状 RNA 对 AR 表达和 AR 信号转导的调节作用,以及 AR 对其表达的影响的现有数据。认识到非编码 RNA 和 AR 之间复杂的相互作用在设计新的治疗选择以及调节对传统治疗的反应方面具有实际意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76c7/8619311/aea5c761535d/cells-10-03198-g001.jpg

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