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NRF2 与远端增强剂相互作用,并在KRAS驱动的胰腺癌细胞中抑制氧化合成酶2的表达
Eros Di Giorgio1, Ylenia Cortolezzis1, Nicolò Gualandi1
1Department of Medicine, Laboratory of Biochemistry, P.le Kolbe 4, 33100 Udine, Italy.
Biochimica et biophysica acta. Molecular cell research
|October 18, 2023
概括
核因素红色素2相关因子2 (NRF2) 在胰腺癌中抑制可诱导的氧化合成酶 (NOS2). 丢失NRF2激活NOS2,增加癌细胞恶性和侵入性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 氧化 (NO) 是一种信号分子,与癌症有关.
- 诱导性氧化合成酶 (NOS2) 在瘤开始和进展中起作用.
- 转录因子NRF2参与细胞对氧化应激反应.
研究的目的:
- 研究胰腺癌细胞中NRF2和NOS2之间的调节关系.
- 阐明这种相互作用在癌细胞恶性和侵入性中的作用.
主要方法:
- RNA测序 (RNA-seq) 是指RNA的测序.
- 染色体免疫沉降测序 (ChIP-seq) 是一种
- 定量逆转录PCR (qRT-PCR) 是一种方法.
- 生物信息学分析分析
- 小干扰RNA (siRNA) 的淘汰方式
- 3D球形形成试验.
- 马特里格尔入侵检测试验
主要成果:
- NRF2通过保持远端增强剂处于不活跃状态来作为NOS2的抑制剂.
- 删除NRF2导致增强剂激活和增加NOS2表达.
- 在NRF2-贫乏的胰腺癌细胞中,NOS2和NO促进了上皮细胞向介质细胞的转变 (EMT).
- 抑制NOS2阻断了NRF2缺乏的胰腺管腺癌 (PDAC) 细胞的入侵.
结论:
- NRF2是胰腺癌中NOS2的抑制剂.
- NRF2直接结合并禁用一个NOS2增强剂,需要NRF2抑制NOS2激活.
- NOS2对于NRF2贫乏的胰腺癌细胞的恶性和侵入性至关重要.
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