作为癌症治疗的分子标,PVRL4的表达是由FOS转录调节的
Tomoyuki Nanamiya1, Kiyoko Takane1, Kiyoshi Yamaguchi1
1Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo 108‑8639, Japan.
Oncology reports
|December 8, 2023
概括
该研究发现,FOS调节了乳腺癌细胞中PVRL4 (nectin-4) 的表达. 这一发现可能解释了 PVRL4 的升高如何影响癌细胞对细胞因子和免疫系统的反应.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
背景情况:
- 在各种癌症中,PVRL4 (nectin-4) 被上调,是像恩福图马布 (enfortumab) 韦多丁 (vedotin) 等疗法的标.
- 导致癌症,特别是乳腺癌PVRL4表达升高的机制尚不清楚.
研究的目的:
- 研究乳腺癌细胞中PVRL4表达升高背后的调节机制.
- 为了确定参与PVRL4基因调节的特定转录因子.
主要方法:
- 用转化酶可访问的染色体测序 (ATAC-seq) 和染色体免疫沉测序 (ChIP-seq) 来确定调控区域.
- 使用ChIP试验和报告者试验验证了FOS与PVRL4增强剂的相互作用.
- 在用PVRL4小干扰RNA治疗的细胞上进行了RNA测序 (RNA-seq).
主要成果:
- 在乳腺癌细胞中发现了一种调节PVRL4的增强器区域.
- 发现FOS与这种PVRL4增强器区域相互作用,FOS结合基因的改变降低了记者活性.
- 外源性FOS表达增加了乳腺癌细胞中的记者活性和PVRL4表达.
- PVRL4与细胞因子反应和免疫系统调节有关.
结论:
- 在乳腺癌中,FOS在调节PVRL4表达方面发挥作用.
- 增加PVRL4表达可能会影响乳腺癌细胞对细胞因子和免疫信号的反应.
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