UBR7和PRMT5之间的相互作用通过调节糖解和免疫微环境来驱动PDAC对凝素的耐药性
Maoxiao Feng1, Qinlian Jiao1, Yidan Ren1
1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
Cell death & disease
|October 18, 2024
概括
研究人员确定了UBR7-PRMT5轴对于胰腺癌中凝胺耐药性至关重要. 针对这一轴可能会克服药物耐药性,并改善胰腺癌治疗.
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:
- 胰腺管腺癌 (PDAC) 是一种致命的消化道恶性瘤.
- 耐吉他的耐药性显著限制了晚期胰腺癌的治疗疗效.
- 在PDAC中基因的基因机制仍然在很大程度上是未知的.
研究的目的:
- 为了研究胰腺癌中杰姆西塔宾耐药性的分子机制.
- 为了确定关键的基因和途径参与调解耐药性gemcitabine.
- 探索潜在的治疗点,以克服PDAC.中的格姆西塔宾耐药性.
主要方法:
- 使用ATAC-seq,ChIP-seq和RNA-seq在胰腺癌患者衍生瘤异种移植 (PDX) 模型上.
- 在对gemcitabine敏感和耐药PDX模型中比较染色质可访问性和基因表达.
- 研究了UBR7的功能作用及其在胰腺癌细胞中与PRMT5的相互作用.
主要成果:
- 发现了与凝胺耐药性相关的染色质可访问性的显著变化.
- 确定了UBR7作为PDAC中gemcitabine耐药性的关键调解者.
- 证明UBR7的耗尽可以通过增加PRMT5的稳定性和促进糖解来增强胰腺癌发生和免疫抑制.
- 表明PRMT5抑制剂 (DS-437) 有效地降低了凝胺耐药性.
结论:
- UBR7-PRMT5信号轴是胰腺管道腺癌中关键的代谢调节器.
- 这个轴在调解凝抗药性方面发挥着关键作用.
- 准UBR7-PRMT5轴是一个有希望的治疗策略,用于克服PDAC中的gemcitabine耐药性.
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