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抑制KDM1A/LSD1可以提高卵巢癌的化疗反应

Yihong Chen^1,2, Jessica D Johnson¹, Sridharan Jayamohan¹

¹Department of Obstetrics and Gynecology, UT Health San Antonio, San Antonio, Texas, USA.

Molecular carcinogenesis

|July 11, 2024

概括

与化疗一起抑制氨酸特异性基因组脱甲酶1A (KDM1A) 显示出治疗卵巢癌 (OCa) 的前景. 这种组合疗法增强了药物敏感性,并在临床前模型中减少了瘤生长.

科学领域:

在瘤学瘤学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
妇科癌症妇科癌症

背景情况:

卵巢癌 (OCa) 是最致命的妇科癌症,由于获得的耐药性,标准基化疗往往失败.
氨酸特异性基因组脱甲酶1A (KDM1A/LSD1),一种表观遗传修饰剂,在OCa中过度表达,但其在化学抵抗中的作用尚不清楚.

研究的目的:

为了研究KDM1A在OCa化学抵抗中的作用.
为了确定KDM1A抑制是否可以提高OCa标准化疗的疗效.

主要方法:

对KDM1A表达与化疗反应相关的TCGA数据集的分析.
用化疗治疗的OCa细胞中KDM1A表达的西部斑分析.
在OCa细胞中KDM1A敲除 (KD) 或抑制和化学敏感性的评估.
RNA测序 (RNA-seq) 用于分析基因表达变化.
在体内研究中,使用了正体OCa异种移植模型.

主要成果:

高KDM1A表达与OCa患者对化疗反应不佳相关.
化疗药物增加了OCa细胞中的KDM1A表达.
KDM1A KD或抑制使OCa细胞对西斯,碳和帕克利塔塞尔敏感,降低活力并增加亡.
抑制KDM1A逆转了化疗诱导的上调表皮质-介质细胞转换 (EMT) 和NF-κB通路基因.
结合KDM1A KD和西斯丁,在体内显著降低了瘤生长.

结论:

KDM1A在OCa化学抵抗中发挥着至关重要的作用.
抑制KDM1A与标准化疗相结合,代表了对卵巢癌的有希望的治疗策略.
向KDM1A可能会克服化学抗药性并改善OCa的治疗结果.

关键词:

在KDM1A中,KDM1A是KDM1A.一个LSD1一个LSD1 化疗化疗是一种化学疗法.卵巢癌是发生在卵巢的癌症.

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