AP-1通过弥合促进剂-增强剂相互作用,促进肺癌细胞中的瘤转录
Xianglong Tan1, Michael Kroneberg2, Fei Sun2
1Department of Biological Chemistry and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. xianglongtan@mednet.ucla.edu.
像AP-1这样的转录因子通过增强促进剂-增强剂相互作用来驱动肺癌中的癌基因表达. 抑制AP-1可以降低瘤转录,并改善非小细胞肺癌患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 了解转录因子在肺癌癌基因表达中的作用至关重要.
- 异常的基因调节驱动非小细胞肺癌 (NSCLC) 的发展和进展.
研究的目的:
- 研究转录因子调节NSCLC中的基因表达的机制.
- 为了确定特定的转录因子及其基因组相互作用驱动肺癌瘤发生.
主要方法:
- 综合的多原子分析包括促进物捕获Hi-C (pcHiC),ATAC-seq,ChIP-seq和转录组学.
- 利用了与癌症基因组图谱 (TCGA) 患者数据验证的癌症细胞系模型.
- 使用药理抑制剂来评估转录因子抑制的功能影响.
主要成果:
- 在肺癌细胞中发现了AP-1转录因子的异常激活.
- AP-1激活与NSCLC患者的不良结果相关,特别是肺状细胞癌.
- 已证明AP-1通过增强的促进剂-增强剂相互作用来调节瘤基因的上调.
结论:
- AP-1在驱动NSCLC中的瘤转录中发挥着关键作用.
- 转录因子通过调节3D基因组结构和促进剂-增强剂循环来调节基因表达.
- 针对AP-1或其上游途径为NSCLC提供了潜在的治疗策略.
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