拷贝数变化影响口腔状细胞癌的电离辐射敏感性
Tadahide Izumi1,2, Piotr Rychahou2,3, Li Chen2,4
1Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Cells
|October 27, 2023
概括
拷贝数变化 (CNVs) 在癌症影响辐射抵抗. 与CNVs相关的PRMT5和APE1的高表达与生存率低下和放射电阻相关,表明治疗点.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 辐射瘤学 辐射瘤学
背景情况:
- 基因组不稳定性,包括拷贝数变异 (CNVs),是癌症的标志.
- CNVs在获得的放射电阻中的作用在很大程度上是未知的.
- PRMT5和APE1是位于14号染色体上的DNA修复基因.
研究的目的:
- 研究CNVs对PRMT5和APE1.1表达的影响.
- 确定PRMT5/APE1表达,CNV和口腔状细胞癌 (OSCC) 患者结局之间的关联.
- 评估PRMT5和APE1对放射电阻的影响.
主要方法:
- 在OSCC患者中分析PRMT5和APE1的TCGA基因组学数据.
- 对基因表达,CNV和临床结果的相关性分析.
- 在体外和体内实验评估DNA修复和PRMT5/APE1调制后的放射敏感性.
主要成果:
- PRMT5和APE1在OSCC组织中表现出高度相关的CNV和表达.
- 高的PRMT5和APE1表达水平与辐射治疗后的生存率低下有关.
- 同时降低PRMT5和APE1的调节,导致DNA修复受损,辐射敏感性增加.
结论:
- 在PRMT5-APE1区域的CNV显著影响癌细胞的放射电阻.
- 在该地区对CNV进行分析,可以阐明所获得的放射电阻的机制.
- 联合抑制PRMT5和APE1可以提高放射治疗的疗效.
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