BPTF通过增强染色质可访问性和稳定AR-FOXA1相互作用来调节雄激素受体活性
Hee-Young Jeon1,2, Sudeep Khadka1,2, Majid Pornour1,2
1Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD, USA.
Nature communications
|December 11, 2025
概括
含基蛋白蛋白1 (BPTF) 在前列腺癌 (PCa) 中被上调,并通过增强雄激素受体 (AR) 信号来推动进展. 抑制BPTF的作用
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 含原蛋白蛋白1 (BPTF) 是核细胞重塑因子 (NURF) 复合体的关键组成部分.
- 在前列腺癌 (PCa) 进展中BPTF的作用,特别是在抵抗割的PCa (CRPC) 中,尚不清楚.
研究的目的:
- 调查BPTF在前列腺癌进展中的作用.
- 阐明BPTF影响PCa中的雄激素受体 (AR) 信号传递的分子机制.
主要方法:
- RNA测序 (RNA-seq) 用于分析基因表达变化.
- 染色体免疫沉测序 (ChIP-seq) 用于评估AR结合.
- 使用测序 (ATAC-seq) 测定转化酶可访问的染色质,以评估染色质的可访问性.
- 同免疫沉试验用于研究蛋白质与蛋白质相互作用.
主要成果:
- 在CRPC中,BPTF是上调调的,通过增强AR基因表达来促进疾病的进展.
- 通过增加染色质可访问性,BPTF促进AR与DNA结合,部分通过SMARCA1.
- BPTF与AR和FOXA1形成一个复合体,FOXA1招募复合体,BPTF稳定相互作用.
- BPTF的基因对其与AR的相互作用至关重要,其抑制抑制PCa细胞生长.
结论:
- 在前列腺癌中,BPTF作为AR活性的关键调节者.
- 通过提高染色质可访问性和稳定AR-FOXA1复合体,BPTF促进AR信号传递.
- 在前列腺癌治疗中,BPTF是一个有前途的治疗标.
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