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多梳抑制复合物 2 在乳腺癌中的功能(综述)。

Polycomb repressor complex 2 function in breast cancer (Review).

机构信息

Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1, Canada.

出版信息

Int J Oncol. 2020 Nov;57(5):1085-1094. doi: 10.3892/ijo.2020.5122. Epub 2020 Sep 17.

Abstract

Epigenetic modifications are important contributors to the regulation of genes within the chromatin. The polycomb repressive complex 2 (PRC2) is a multi‑subunit protein complex that is involved in silencing gene expression through the trimethylation of lysine 27 at histone 3 (H3K27me3). The dysregulation of this modification has been associated with tumorigenicity through the increased repression of tumour suppressor genes via condensing DNA to reduce access to the transcription start site (TSS) within tumor suppressor gene promoters. In the present review, the core proteins of PRC2, as well as key accessory proteins, will be described. In addition, mechanisms controlling the recruitment of the PRC2 complex to H3K27 will be outlined. Finally, literature identifying the role of PRC2 in breast cancer proliferation, apoptosis and migration, including the potential roles of long non‑coding RNAs and the miR‑200 family will be summarized as will the potential use of the PRC2 complex as a therapeutic target.

摘要

表观遗传修饰是调节染色质中基因的重要因素。多梳抑制复合物 2(PRC2)是一种多亚基蛋白复合物,通过组蛋白 3(H3)赖氨酸 27 的三甲基化(H3K27me3)参与基因表达沉默。这种修饰的失调与肿瘤发生有关,通过凝聚 DNA 来减少肿瘤抑制基因启动子中转录起始位点(TSS)的可及性,从而增加肿瘤抑制基因的抑制。在本综述中,将描述 PRC2 的核心蛋白以及关键辅助蛋白。此外,还将概述控制 PRC2 复合物募集到 H3K27 的机制。最后,将总结 PRC2 在乳腺癌增殖、凋亡和迁移中的作用,包括长非编码 RNA 和 miR-200 家族的潜在作用,以及 PRC2 复合物作为治疗靶点的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/435e/7549536/d1aab054ced3/IJO-57-05-1085-g00.jpg

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