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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

FANCI沉默促进DNA损伤并使卵巢癌细胞对卡铂敏感

卷 22, 期 7, 2022

发表于: 23 May, 2022

页: [591 - 602] 页: 12

弟呕挨: 10.2174/1568009622666220331091709

价格: $65

摘要

背景: 卵巢癌（OVCA）在同源重组（HR）中具有独特的表观遗传学改变和缺陷。尽管最初对铂类化疗敏感，HR功能失调的肿瘤最终获得耐药性。范科尼贫血（FA）的特征是骨髓衰竭（BMF）和消除DNA链间交联（ICL）的能力降低。然而，在OVCA中FANCI介导的耐药机制尚不清楚。 摘要: 我们探索确定FANCI是否参与OVCA中的化疗耐药 方法:使用TIMER和cBioPortal分别分析FANCI表达和表观遗传学改变。使用Kaplan-Meier绘图仪、GSE63885和TCGA-OVCA数据集分析FANCI表达与OVCA患者生存率之间的相关性。免疫组化检测OVCA中FANCI的表达。通过CCK-8和Transwell评估FANCI抑制细胞中的细胞增殖、迁移和侵袭。流式细胞术和免疫荧光法检测细胞凋亡和DNA损伤。同时，用caspase GloR 3/7试剂盒检测caspase 3/7的活性。此外，通过Western blot检测FANCI、γH2AX和凋亡效应子的表达。 结果: FANCI在OVCA中有拷贝数变异（CNV）。OVCA患者FANCI的高表达与低生存率相关。此外，FANCI表达与OVCA的化疗反应相关。卡铂以时间依赖性方式诱导OVCA细胞中FANCI的表达。FANCI的沉默对细胞增殖没有影响，但阻碍OVCA细胞迁移和侵袭。机械地，FANCI的敲除通过CHK1/2-P53-P21途径增强DNA损伤诱导的凋亡。 结论: FANCI可能是OVCA患者的潜在治疗靶点。

关键词: FANCI, FANCD2, 卵巢癌，化疗耐药，DNA损伤， P53.

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