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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

通过与VDAC1相互作用调节线粒体钙摄取并促进子宫内膜癌进展的线粒体钙单转运蛋白(MCU

卷 24, 期 3, 2024

发表于: 27 September, 2023

页: [354 - 367] 页: 14

弟呕挨: 10.2174/1568009624666230912095526

价格: $65

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摘要

背景:虽然子宫内膜癌是一种常见的女性生殖道恶性肿瘤，但我们对控制子宫内膜癌的因素知之甚少。 目的:探讨MCU在子宫内膜肿瘤发生中的作用及其分子机制。 材料与方法:共纳入94例子宫内膜癌患者。采用免疫组化和免疫荧光法检测肿瘤组织和正常组织中MCU和VDAC1的表达。评估MCU和VDAC1表达与临床病理特征的关系。转染靶向MCU或全长MCU质粒的shRNA后，Ishikawa和RL95-2细胞分别出现克隆形成、伤口愈合、transwell和MitoTracker Red染色。此外，利用Western blotting或免疫荧光检测VDAC1敲低和/或MCU过表达或敲低时MCU、VDAC1、Na+/Ca2+/Li+交换剂(NCLX)和β-catenin的表达。 结果:MCU和VDAC1表达在子宫内膜癌组织中显著上调，且与组织学分级、子宫肌层浸润深度和淋巴结状态显著相关。MCU上调可增强子宫内膜癌细胞的克隆形成、迁移和线粒体活性。当MCU被静音时，结果与之相反。MCU或VDAC1沉默降低了MCU、VDAC1、NCLX和β-catenin的表达。此外，VDAC1敲低可减轻MCU过表达对上述蛋白的促进作用。 结论:本研究表明mcu诱导的线粒体钙摄取通过与VDAC1的相互作用在子宫内膜肿瘤发生中起关键作用。

关键词: 子宫内膜癌，MCU, VDAC1，增殖，迁移，线粒体膜电位，线粒体钙摄取。

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