死细胞改变IRE1α-XBP1信号,并诱导质母细胞瘤的转录变化
Jiwoo Lim1,2, Seulgi Lee1, Ye-Seon Hong1
1Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.
International journal of molecular sciences
|January 10, 2026
概括
性质母细胞细胞通过损害IRE1α-XBP1通路激活来破坏内质网膜应激信号,导致转录性变化,可能导致瘤进展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞应激反应的应激反应
背景情况:
- 亡是多形质母细胞瘤 (GBM) 的标志,与炎症和不良预后有关.
- 死细胞死亡对内分泌网膜 (ER) 压力信号的影响在GBM中仍然不太清楚.
研究的目的:
- 研究死细胞对ER应激信号和人类质母细胞瘤细胞系中未折叠蛋白质反应 (UPR) 的影响.
- 阐明死细胞影响GBM细胞行为的分子机制.
主要方法:
- 人类质母细胞瘤细胞系暴露于死细胞.
- 对ER应激信号通路 (IRE1α,PERK,ATF6) 和UPR标记物的分析.
- 对IκBα酸化,自降解和PKAc酸化的评估.
- 转录基因分析和定量逆转录PCR (qRT-PCR).
- 在XBP1中进行了敲击实验.
主要成果:
- 死细胞减少了IRE1α酸化,增加了未连接的XBP1 (XBP1u) 积累,选择性地影响了IRE1α-XBP1通路.
- 死亡细胞对PERK和ATF6通路没有影响.
- 死细胞增强IκBα酸化,并降低了自细胞的降解.
- ER应激诱导剂没有逆转XBP1u积累;观察到减少PKAc酸化和IRE1α激活.
- 转录组分析揭示了XBP1相关基因的改变表达,在XBP1敲击后出现了类似的变化和加剧的影响.
结论:
- 死亡细胞在质母细胞瘤中破坏了正规的IRE1α-XBP1信号传递.
- 死细胞在质母细胞瘤细胞中诱导显著的转录重编程.
- 这些分子变化可能会导致质母细胞瘤的进展和不良的临床结果.
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