在乳腺癌中,27-基胆固醇通过雌激素受体α抑制G9a的表达
Ravindran Vini1,2, Asha Lekshmi3, Swathy Ravindran1
1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, India.
Journal of cellular and molecular medicine
|August 24, 2023
概括
胆固醇代谢物27-基胆固醇 (27-HC) 抑制G9a表达并减少H3K9me2标记,促进乳腺癌的进展和入侵. 这种表观遗传调节会影响瘤生长和转移.
科学领域:
- 生物化学 生物化学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 27胆固醇 (27-HC) 是一种内源性胆固醇代谢物和选择性雌激素受体调节器 (SERM).
- 27-HC在乳腺癌中表现出增殖和转移性活性.
- 27-HC对乳腺癌表观遗传特征的影响在很大程度上是未知的.
研究的目的:
- 研究27-HC是否调节乳腺癌中的表观遗传特征.
- 阐明27-HC在调节基因表达和乳腺癌进展中的表观遗传修饰中的作用.
主要方法:
- 对G9a表达和H3K9me2水平进行定量分析.
- 染色体免疫沉测序 (ChIP-seq) 用于H3K9me2.2.进行测序.
- 乳腺癌患者组织的免疫组合化学分析.
- 在G9a促销器的雌激素受体α (ERα) 占用率分析.
主要成果:
- 27-HC抑制了 euchromatic 基因组合素氨酸甲基转移酶 G9a 的表达.
- 27-HC降低了与癌症进展,扩散和转移相关的基因上的H3K9me2水平.
- 在G9a促进体上的ERα占用减少了27-HC,表明转录抑制.
- 在27-HC治疗后观察到H3K9me2向基因的升级.
- 在患者组织中发现了G9a表达和CYP7B1之间的正相关性.
结论:
- 27-HC通过ERα介导的转录抑制来负面调节G9a的表达.
- 在H3K9me2表观遗传标记的27-HC诱导的减少促进乳腺癌瘤发生和入侵.
- 这些发现揭示了一个新的表观遗传机制,27-HC有助于乳腺癌的进展.
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