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通过DNA-PKcs激酶活性对基因表达的基底和以太化物诱导的变化的比较分析

Sk Imran Ali¹, Mohammad J Najaf-Panah¹, Kennedi B Pyper¹

¹Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, United States.

Frontiers in genetics

|April 5, 2024

概括

DNA-PKcs 激酶活性抑制了DNA损伤后的炎症. 基因酶不活性DNA-PKcs导致炎症反应增加,影响癌症治疗策略.

科学领域:

分子生物学分子生物学
遗传学是一个遗传学.
细胞生物学细胞生物学

背景情况:

基因组维护对细胞生存至关重要;DNA损伤反应缺陷与癌症和神经系统疾病有关.
DNA-蛋白激酶催化子单元 (DNA-PKcs) 对于DNA修复和基因表达调节至关重要.
它在调节细胞对DNA损伤反应中的作用至关重要.

研究的目的:

为了研究野生类型 (WT) 与激酶不活性 (KR) DNA-PKcs.的细胞中的全球基因表达变化.
了解在DNA-PKcs激酶活性存在或不存在的情况下对DNA损伤的转录反应.
为了确定受DNA-PKcs状态影响的关键转录调节者.

主要方法:

全球基因表达分析使用在WT和KRDNA-PKcs细胞上的RNA测序.
评估未经处理的细胞和以太胺诱导的DNA损伤后的转录变化.
途径分析以确定主转录调节剂和qPCR进行验证.

主要成果:

基因酶不活性DNA-PKcs细胞显示出不同的基因表达特征,特别是与WT细胞相比,炎症反应加剧.
下调基因主要参与两种基因型的生物合成途径.
途径分析揭示了对组织素修饰,炎症,细胞循环,Wnt/β-catenin信号传递和细胞发育的调节者的显著影响.

结论:

DNA-PKcs 激酶活性对于抑制基因毒性压力后的促炎信号是必不可少的.
了解抑制DNA-PKcs激酶活性的转录后果对于优化结合DNA破坏剂和DNA-PK抑制剂的癌症疗法至关重要.

关键词:

修复DNA损伤的修复这就是DNA-PKcscs.这里是etoposide的位置.基因表达的基因表达方式不同类的末端连接.转录组 (transcriptome) 是一个转录组.

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