在胃癌中,JUNB通过染色质可访问性和转录基因分析通过MAPK信号通路调解氧沙抗性
Suyao Li1, Yichou Wei1, Xun Sun1
1Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Acta biochimica et biophysica Sinica
|June 20, 2023
概括
在胃癌中,JUNB过度表达通过激活MAPK通路驱动了oxaliplatin耐药性. 抑制JUNB或使用MAPK抑制剂与oxaliplatin一起可以恢复敏感性并改善患者的预后.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 基于的化疗,包括氧沙,是晚期胃癌的标准.
- 化疗耐药性显著限制了治疗疗效和患者的存活率.
- 了解抵抗机制对于开发有效的治疗策略至关重要.
研究的目的:
- 阐明在胃癌中抗氧化的分子机制的基础.
- 为了确定克服抗氧化抗性的关键分子标.
主要方法:
- 产生一种抗氧沙的胃癌细胞系.
- 检测转化酶可访问的染色体测序 (ATAC-seq) 和RNA测序 (RNA-seq).
- 染色体免疫沉降测序 (ChIP-seq) 和组织微阵列分析.
主要成果:
- 在耐药细胞中确定了3232个具有更高可访问性的基因组区域,这意味着JUNB是核心转录因子.
- 抗性细胞中JUNB过度表达与胃癌预后不佳相关.
- JUNB激活了MAPK信号通路,调解了氧化抗性.
结论:
- 通过MAPK通路激活,JUNB在胃癌中介于oxaliplatin耐药性方面发挥着关键作用.
- 准JUNB或将MAPK抑制剂与牛酸结合,提供了一种有前途的战略,以克服耐药性并改善患者的治疗结果.
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