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通过诱导p53-介导的核应力,RPS15a敲击阻碍了B-ALL的进展

Xinxin Li¹, Sijia Di², Fengze Nie²

¹Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710114, China; Shenzhen Research Institute of Northwestern Polytechnical University, Shenzhen, 518000, China.

Biochemical and biophysical research communications

|April 16, 2025

概括

一种核糖体蛋白质RPS15a在B细胞急性淋巴细胞白血病 (B-ALL) 中表达高. 它的淘汰会损害B-ALL细胞的生长,并通过p53信号诱导核应激,这表明RPS15a是治疗点.

科学领域:

分子生物学分子生物学
癌症生物学癌症生物学
血液学血液学血液学

背景情况:

核糖体生物发生对于细胞生长至关重要,并与B细胞急性淋巴细胞白血病 (B-ALL) 病原发生有关.
在B-ALL中,对核糖体生物发生的精确调节机制尚不完全理解.

研究的目的:

调查RPS15a在B-ALL进展中的作用.
阐明RPS15a影响B-ALL细胞行为和核细胞功能的分子机制.

主要方法:

在B-ALL患者中确定了RPS15a表达水平.
在B-ALL细胞中进行RPS15a淘汰 (KD).
评估了细胞增殖,细胞循环和细胞亡.
使用核蛋白 (NPM1,FBL) 的免疫光染色.
分析了核糖体RNA (rRNA) 的合成和处理.
研究了p53信号通路的激活.
通过p53敲击 (KD) 进行了救援实验.

主要成果:

在B-ALL中,RPS15a被显著上调.
RPS15a KD抑制了B-ALL细胞的增殖,细胞周期的进展,并诱导了细胞亡.
RPS15a KD 破坏了核结构,改变了 NPM1/FBL 的定位,并触发了核应激.
RPS15a KD抑制了rRNA的合成和处理.
RPS15a的耗尽激活了p53信号通路,增加了p53和p21的表达.
p53 KD 挽救了 RPS15a KD 对核糖体生物发生,细胞循环和亡的影响.

结论:

在B-ALL的进展中,RPS15a起着至关重要的作用.
RPS15a通过p53信号介导的核应力来调节B-ALL.
RPS15a代表了B-ALL治疗的潜在治疗标.

关键词:

B-ALL,所有的人.核状应激压力核状应激压力在RPS15a中使用RPS15a.p53 信号传输信号传输

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