Oncogene:BCOR偶联H2A单泛素化来抑制雄激素受体靶标基因来调控前列腺癌增殖

2020-01-20 AlexYang MedSci原创

有研究人员已经鉴定了BCL6共阻遏物(BCOR)是一个激素依赖的雄激素受体(AR)互作伴侣,并且是正常前列腺和癌变前列腺发展的关键转录因子。BCOR在癌症和血液疾病中经常突变,并且是非典型多梳抑制复合物1(ncPRC1.1)的组分,对细胞分化的多个方面是需要的。然而,其在雄激素信号或者前列腺癌细胞中的作用仍旧未知。最近,有研究人员利用全基因组分析的方法阐释了在去势难治性前列腺癌(CRPC)中,BC

有研究人员已经鉴定了BCL6共阻遏物(BCOR)是一个激素依赖的雄激素受体(AR)互作伴侣,并且是正常前列腺和癌变前列腺发展的关键转录因子。BCOR在癌症和血液疾病中经常突变,并且是非典型多梳抑制复合物1(ncPRC1.1)的组分,对细胞分化的多个方面是需要的。然而,其在雄激素信号或者前列腺癌细胞中的作用仍旧未知。

最近,有研究人员利用全基因组分析的方法阐释了在去势难治性前列腺癌(CRPC)中,BCOR在大多数的AR结合染色质位点中都以雄激素依赖的方式被招募。有趣的是,BCOR的缺失对于细胞增殖调控、分化和发育有关的雄激素抑制基因的表达具有显著的影响。这些基因的许多基因,比如HOX基因,其缺失能够导致H2A K119单泛素化减少以及mRNA表达的增加。一致的是,BCOR缺失能够损伤CRPC细胞的增殖和生存,并诱导它们的凋亡。

最后,研究人员指出,他们的数据表明了BCOR-ncPRC1.1复合物在共阻遏一系列AR靶基因中以及前列腺癌细胞增殖调控中的关键作用。

原始出处:

Joanna K. Lempiäinen, A. B. M. Kaiser Manjur, Marjo Malinen et al. BCOR-coupled H2A monoubiquitination represses a subset of androgen receptor target genes regulating prostate cancer proliferation. Oncogene. 10 Jan 2019

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    2020-02-07 cy0324
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    2020-01-22 zhaojie88
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    2020-01-22 zsyan
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    2020-01-21 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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