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基脱甲酶KDM5D上调导致结肠癌的性别差异
Jiexi Li1, Zhengdao Lan1, Wenting Liao1,2
1Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nature
|June 21, 2023
概括
男性性别和KRAS突变通过Y染色体基因KDM5D驱动结直肠癌 (CRC) 的转移. 针对KDM5D提供了一种治疗策略,以减少男性KRAS突变CRC的转移.
科学领域:
- 癌症学
- 遗传学
- 分子生物学
背景情况:
- 性行为对癌症,特别是结肠直肠癌 (CRC) 有很大影响,男性的死亡率更高.
- 在CRC中性别差异的分子基础,特别是在KRAS突变病例中,仍然不太清楚.
研究的目的:
- 阐明导致KRAS突变结直肠癌 (CRC) 性差异的分子机制.
- 确定可操作的治疗点,以减少KRAS突变CRC的男性患者的转移.
主要方法:
- 使用一种可诱导的瘤性KRAS和瘤抑制基因删除的小鼠CRC模型 (iKAP).
- 进行了跨物种的综合分子和转录组分析.
- 研究了Y染色体基因KDM5D在CRC进展和转移中的作用.
主要成果:
- 在男性中,KRAS突变CRC的转移率和死亡率较高.
- Y染色体基因KDM5D被确定为KRAS- STAT4信号的上调.
- 干扰KDM5D损害了紧密的结节,增加了侵入性,并减少了CD8+T细胞的死亡.
- 构成性KDM5D表达在体内促进了更多的侵入性瘤.
结论:
- 通过KRAS*-STAT4调节的Y染色体KDM5D显著导致KRAS*CRC的性别差异.
- 破坏了癌细胞的粘附和瘤免疫力,促进了转移.
- 针对KDM5D是一种治疗策略,可降低KRAS* CRC男性的转移风险.
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