通过招募染色体化酶DNA结合蛋白1的ESS2控制前列腺癌的进展
Sayuri Takahashi1,2, Ichiro Takada3,4, Kenichi Hashimoto5
1Department of Urology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan. t-sayuri@athena.ocn.ne.jp.
Scientific reports
|July 31, 2023
概括
转录性核心调节器ESS2驱动前列腺癌的生长和进展. 向ESS2提供了一种新的表观遗传治疗策略,用于割耐性前列腺癌 (CRPC).
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 多 (ADP-ribose) 聚合酶抑制剂改善了割抵抗性前列腺癌 (CRPC) 的存活率,但只在具有特定突变的患者中有效.
- 需要在CRPC治疗中发现针对表观遗传调节器的新药.
研究的目的:
- 为了研究转录性核心调节器ESS2在前列腺癌中的作用.
- 评估ESS2作为CRPC的潜在治疗点.
主要方法:
- 在PC3细胞中ESS2倒置和随后在裸体小鼠中进行瘤异种移植研究.
- 微阵列分析以确定ESS2调节基因.
- 染色体免疫沉测试用于评估蛋白质招募和基因组修饰.
- 在Tamoxifen诱导的Ess2-Knockout小鼠中分析前列腺发育.
主要成果:
- 在体内,ESS2倒置显著抑制了前列腺癌细胞的增殖.
- ESS2调节关键的与癌症相关的基因,包括那些涉及染色体酶DNA结合蛋白1 (CHD1),PPAR-γ,WNT5A和TGF-β的基因.
- 减少核因子 (NF) -κB/CHD1招募和H3K36me3水平在目标基因促进体.
- ESS2增强NF-κB,NFAT和SMAD2/3.3的转录活动.
- 在小鼠中,Ess2 缺乏导致前列腺发育延迟和细胞异常.
结论:
- 在前列腺癌中,ESS2 起到关键的转录性核心调节作用.
- ESS2代表了一种有前途的新型表观遗传治疗割抵抗性前列腺癌 (CRPC) 的目标.
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