lncRNA PTCSC1 在HCT116和SW480细胞中通过FOXO3a通路促进TRAIL抵抗
Changcheng Wang1, Jia Guo2, Zengan Wu3
1General Surgery Diagnosis and Treatment of Diseases and Comprehensive Treatment of Tumor, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Haidian District, Beijing 100091, China.
概括
长非编码RNA PTCSC1过度表达通过DR4/AKT/FOXO3a通路抑制亡,促进结肠直肠癌 (CRC) 抵抗TNF相关的亡诱导连接体 (TRAIL) 疗法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 结肠直肠癌 (CRC) 是一个重大的全球健康挑战,死亡率高.
- 与TNF相关的诱导亡联体 (TRAIL) 疗法显示出有前途,但在许多CRC患者中面临阻力.
- 长非编码RNA PTCSC1在CRC中TRAIL抗性的作用在很大程度上仍未被阐明.
研究的目的:
- 研究PTCSC1在TRAIL抗性结直肠癌 (CRC) 中的作用.
- 探索导致CRC中PTCSC1-介导的TRAIL抗性的潜在分子机制.
主要方法:
- 在TRAIL敏感和TRAIL抗性CRC细胞系中对PTCSC1表达的比较分析 (HCT116,SW480,HT-29,caco-2).
- 评估PTCSC1对TRAIL诱导的亡的影响.
- 研究PTCSC1对死亡受体4 (DR4) 的表达以及AKT和FOXO3a信号通路的激活的影响.
主要成果:
- 发现PTCSC1在与TRAIL敏感细胞相比,在抗TRAIL的CRC细胞中过度表达.
- 增加的PTCSC1表达抑制了TRAIL诱导的亡,而减少的PTCSC1表达增强了它.
- 观察到PTCSC1降低DR4表达的调节,并提高AKT和FOXO3a激活的调节.
结论:
- PTCSC1表达水平与CRC中对TRAIL诱导的亡的敏感性相关.
- 通过调节DR4/AKT/FOXO3a信号通路,PTCSC1有助于CRC中的TRAIL阻力.
- 向PTCSC1可能提供一种治疗策略,以克服结直肠癌中TRAIL抗性.
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