在晚期前列腺癌亚型中,EZH2的血统特定的正规和非正规活性
Varadha Balaji Venkadakrishnan1,2,3, Adam G Presser1, Richa Singh4
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature communications
|August 8, 2024
概括
增强血清同源2 (EZH2) 驱动前列腺癌的进展. 抑制EZH2促进神经内分泌前列腺癌 (NEPC) 的分化,并建议共同向策略来克服抗性.
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:
- 增强体质同源2 (EZH2) 是一种在割抵抗性前列腺癌中过度表达的基因组甲基转移酶.
- EZH2与疾病进展和对荷尔蒙疗法的耐药性有关,使其成为治疗点.
研究的目的:
- 确定EZH2在前列腺腺癌和神经内分泌前列腺癌 (NEPC) 中的特异性作用和差异性活性.
- 了解EZH2在调节差异化和谱系可塑性的作用.
- 为了确定对EZH2抑制剂治疗的反应和耐药性的媒介.
主要方法:
- 研究了EZH2在不同前列腺癌亚型中的作用机制.
- 分析了EZH2抑制对基因表达和细胞分化的影响.
- 检查了对细胞周期基因和潜在的抵抗机制的下游影响.
主要成果:
- EZH2调节双价基因,上调NEPC相关的转录驱动器,如ASCL1和NEPC中的神经元基因程序.
- 在NEPC中抑制EZH2导致向前分化.
- 观察到EZH2抑制对细胞周期基因的亚型特异效应.
结论:
- EZH2在驱动NEPC和调节谱系可塑性方面发挥着至关重要的作用.
- 准EZH2可以诱导NEPC的分化.
- 与环林/CDK抑制剂共同向EZH2可能会在晚期前列腺癌中克服对EZH2抑制的抵抗力.
更多相关视频
10:26Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
Published on: January 16, 2015
8.4K
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
6.9K
相关概念视频
Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Spreading of Chromatin Modifications
8.2K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.2K
