通过与 hnRNPM 相互作用,KHSRP 通过调节 GPX4 表达来保护结直肠癌细胞免受铁亡
Xia Ding1, Ningjing Zhang1, Shuai Zhan2
1Institute of Marine Biology and Pharmacology, Ocean College, Zhejiang University, Zhoushan, 316021, China.
Experimental cell research
|November 1, 2025
概括
高KHSRP表达通过稳定GPX4mRNA来保护结直肠癌细胞免受铁亡. 准这种KHSRP-hnRNPM-GPX4通路可能会在癌症治疗中克服铁灭菌耐药性.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞死亡机制 细胞死亡机制
背景情况:
- 铁亡是依赖铁的细胞死亡,涉及脂质过氧化物.
- KHSRP调节细胞过程,但其在铁亡中的作用尚不清楚.
- 结肠直肠癌 (CRC) 的预后与铁亡调节有关.
研究的目的:
- 调查KHSRP在结肠直肠癌ferroptosis中的作用.
- 阐明KHSRP在ferroptosis中的分子机制.
- 确定CRC铁灭菌耐药性的潜在治疗点.
主要方法:
- 在CRC患者数据中评估KHSRP表达.
- 在CRC细胞中进行KHSRP敲击,观察铁亡标记物 (脂质过氧化,MDA,GSH).
- 通过分子试验研究了KHSRP与hnrnpm的相互作用以及与GPX4mRNA的结合.
主要成果:
- 升高的KHSRP与不良的CRC预后相关.
- 通过增加脂质过氧化和MDA,并降低GSH,KHSRP敲击诱导铁亡.
- KHSRP 与 hnRNPM 相互作用,调节 GPX4 的 mRNA 稳定性,维持 GPX4 的表达.
- 在KHSRP中断后, hnRNPM过度表达挽救了GPX4水平和铁化表型.
结论:
- 通过hnRNPM-GPX4轴,KHSRP保护CRC细胞免受铁亡.
- 在KHSRP-hnRNPM复合体稳定GPX4mRNA后转录.
- 针对KHSRP-hnRNPM-GPX4轴提供了一种潜在的策略来对抗CRC铁灭菌耐药性.
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