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RET 是肠道瘤发生的性别偏差调节剂
Sean T Koester1,2, Naisi Li1, Neelendu Dey1,3,4
1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Frontiers in gastroenterology (Lausanne, Switzerland)
|August 16, 2024
概括
RET原基因以特定性别的方式影响结肠直肠癌 (CRC) 的发展,由肠道微生物群调节. 准RET可能为CRC治疗提供新的途径.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 微生物学 微生物学
背景情况:
- 在结直肠癌 (CRC) 中,RET原型瘤基因起着双重作用,同时作为瘤基因和瘤抑制剂.
- 了解RET信号在CRC发病过程中的作用,特别是与遗传背景和环境因素相关的理解至关重要.
研究的目的:
- 为了研究RET信号在瘤发生中的作用,在Apoc缺乏的CRC临床前模型中.
- 为了确定RET信号是否表现出CRC发育的性别偏差调节.
- 探索肠道微生物对RET介导的CRC瘤发生的影响.
主要方法:
- 使用了一种临床前小鼠模型,该模型缺少Apc,对Ret有异合性 (ApcRet+/-).
- 分析了与性别和微生物群状况相关的瘤负担和基因表达特征.
- 服用抗生素以耗尽微生物群,并评估对瘤发展的影响.
- 重建了微生物组,以评估其在拯救表型中的作用.
主要成果:
- 观察到一个显著的性别偏差的表型:ApcRet+/-女性比男性表现出更大的瘤负担.
- 功能障碍的RET信号与瘤和正常结肠组织中基因表达的改变相关.
- 抗生素治疗逆转了性别偏差,微生物群枯竭的男性显示瘤负担增加.
- 微生物组复合逆转了抗生素诱导的表型,恢复了性别偏差.
结论:
- RET信号作为一个性二态的,微生物组介导的CRC瘤发生的调节器.
- 肠道微生物组显著影响RET在CRC发育中的性别特异性影响.
- 这些发现突出了宿主基因,性别和CRC进展中的微生物群之间的复杂相互作用.
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