希斯H3Y99硫调节了对低氧反应的肝细胞癌
Sibi Yin1, Weixing Yu2, Runxin Zhou1
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
The Journal of biological chemistry
|February 4, 2024
概括
基素H3氨酸-99硫化 (H3Y99sulf) 是肝细胞癌 (HCC) 中的一种新型癌症相关标记. 这种标记通过控制关键基因来调节缺氧反应,抑制瘤生长.
科学领域:
- 表观遗传学和翻译后修改
- 癌症生物学 癌症生物学
- 疾病的分子机制.
背景情况:
- 基因组H3氨酸-99硫化 (H3Y99sulf) 是一种新发现的基因组修饰.
- 它在癌症中的作用,特别是低氧条件下的肝细胞癌 (HCC),仍然在很大程度上未被探索.
- 已知H3Y99硫与H4R3me2a相互作用,影响基因转录.
研究的目的:
- 研究H3Y99硫在肝细胞癌 (HCC) 细胞对低氧反应中的作用.
- 为了阐明涉及H3Y99硫,H4R3me2a和TDRD3在HCC中的分子途径.
- 为了确定针对H3Y99sulf-H4R3me2a-TDRD3轴的治疗潜力.
主要方法:
- 在低氧条件下对HCC细胞中H3Y99硫含量的分析.
- 研究了PAPSS2在低氧刺激的H3Y99硫生成中的作用.
- 研究了TDRD3作为下游效应器的功能,读取H3Y99sulf-H4R3me2a标记.
- 研究了SULT1B1耗尽对H3Y99sulf-H4R3me2a-TDRD3轴和基因表达的影响.
- 评估了破坏这一轴对HCC细胞增殖,瘤生长和生存的影响.
主要成果:
- 在响应低氧的HCC细胞中,H3Y99硫的上调调节,由SNAIL途径和PAPSS2.2介导.
- 双重标记H3Y99sulf-H4R3me2a将TDRD3招募到HIF1A和PDK1的促进者中,调节它们的转录.
- SULT1B1的耗尽减少了H3Y99硫-H4R3me2a-TDRD3复合体的形成,降低了HIF1A和PDK1.
- 这个轴的干扰抑制了关键的低氧反应基因,抑制了HCC的扩散和瘤的生长.
结论:
- H3Y99硫是一种关键的与癌症相关的组织蛋白标记,调解HCC对缺氧的反应.
- H3Y99sulf-H4R3me2a-TDRD3轴是一个关键的调节途径,涉及HIF1A和PDK1在HCC中.
- 针对这一轴提供了一种潜在的治疗策略,以抑制低氧压力下的HCC进展.
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