综合性分析揭示了高度血清性卵巢癌的早期表观遗传变化
Hidenori Machino1,2, Ai Dozen3,4, Mariko Konaka5
1Cancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo, 103-0027, Japan. hidenori.machino@riken.jp.
Experimental & molecular medicine
|October 1, 2023
概括
这项研究揭示了早期表观遗传变化和转录因子失调在高度血清性卵巢癌 (HGSOC) 的发展. MEK 抑制剂疗法在治疗抗化疗性 HGSOC 的治疗方面显示出有前途.
科学领域:
- 妇科瘤学 妇科瘤学
- 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:
- 高度血清性卵巢癌 (HGSOC) 是一种具有良好特征的遗传改变的致命妇科癌症.
- 在早期HGSOC瘤发生过程中表观遗传修饰和转录因子失调仍然不完全理解.
- 研究早期的分子事件对于开发有效的治疗策略至关重要.
研究的目的:
- 为了阐明HGSOC瘤发生中的早期表观遗传变化和转录因子失调.
- 使用整合性奥米克学方法,分析逐步的HGSOC进展.
- 为了确定HGSOC的潜在治疗点.
主要方法:
- 综合性奥米克分析包括ATAC-seq,ChIP-seq和RNA-seq在逐步的HGSOC模型上.
- 确认正常,癌前 (STICs) 和癌症HGSOC组织中的蛋白质表达变化.
- 转录因子动机分析以确定失调的DNA结合活动.
主要成果:
- 在早期瘤发生过程中观察到的AP-1复合体和GATA家族转录因子的失调.
- 增加了JUN和FOSL2,减少了GATA6和DAB2蛋白质,与上皮介质转换 (EMT) 和蛋白质酶体下调相关.
- 在蛋白质酶抑制后,对卡德林集群区域的表观遗传抑制和化学基因基因的上调调节.
- 在HGSOC模型中,MEK抑制剂治疗逆转了瘤原性变化.
结论:
- 早期的HGSOC发育涉及特定的表观遗传变化和转录因子失调.
- 蛋白质酶抑制和随后的化学激素上调可能有助于免疫逃避.
- MEK 抑制剂疗法对一小部分高高血压患者,包括耐化疗患者,显示出潜在的临床有效性.
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