NF-κB表观遗传吸引力景观驱动乳腺癌异质性异质性
Francisco Lopes1,2, Bruno R B Pires3,4, Alexandre A B Lima5
1Universidade Federal do Rio de Janeiro, Campus Duque de Caxias Professor Geraldo Cidade, Duque de Caxias, Brazil. flopes@ufrj.br.
NPJ systems biology and applications
|November 24, 2025
概括
核因子-kappa B (NF-κB) 的表观遗传变异性推动了乳腺癌 (BC) 亚型的转变. NF-κB水平的波动导致HER2+和三阴性乳腺癌 (TNBC) 亚型之间的不可逆转转移,影响治疗耐药性.
科学领域:
- 分子生物学分子生物学
- 系统生物学 系统生物学
- 癌症研究 癌症研究
背景情况:
- 乳腺癌 (BC) 亚型异质性是治疗耐药性和复发的关键驱动因素.
- 瘤异质性源于遗传/表观遗传变化,表型可塑性和微环境选择.
- 了解驱动BC亚型进展的机制对于开发有效的治疗方法至关重要.
研究的目的:
- 调查核因子-kappa B (NF-κB) 表观遗传变异性在HER2+BC进展中的作用.
- 描述BC亚型之间的动态转换.
- 为了建模管理这些亚型相互作用的基因调节网络 (GRN).
主要方法:
- 在HER2+和三阴性乳腺癌 (TNBC) 细胞系中,NF-κB,TWIST1,SIP1和SLUG的量化表达水平.
- 开发并校准了一个GRN模型来模拟转录相互作用.
- 通过计算建模和实验验证 (DHMEQ治疗,患者数据) 分析了表观遗传景观,吸引子盆地和过渡动态.
主要成果:
- GRN模型的表观遗传景观有两个吸引子盆地 (HER2+和TNBC),被一个不稳定的状态隔开.
- 在NF-κB水平的随机波动驱动HER2+和TNBC亚型之间的自发,不可逆转的过渡.
- NF-κB可用性的变化会改变亚型流域大小和过渡概率.
结论:
- NF-κB表观遗传变异性是BC亚型异质性和进展的关键因素.
- 这项研究增强了吸引子景观模型,以了解动态细胞状态过渡.
- 结果为改善BC分类,预后和向治疗策略提供了洞察力.
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