![conference banner](/images/conference-banner.jpeg)
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。
[http://dx.doi.org/10.1038/s41436-019-0536-8] [PMID: 31086306]
[http://dx.doi.org/10.1186/s13046-020-01679-8] [PMID: 32847606]
[http://dx.doi.org/10.1038/s41388-020-01555-x] [PMID: 33208911]
[http://dx.doi.org/10.1016/j.ajog.2020.08.032] [PMID: 32805208]
[http://dx.doi.org/10.1136/ijgc-2020-001822] [PMID: 33082238]
[http://dx.doi.org/10.1016/j.cell.2020.08.049] [PMID: 33035451]
[http://dx.doi.org/10.1016/j.apsb.2016.11.001] [PMID: 28119804]
[http://dx.doi.org/10.1016/j.ceca.2020.102345] [PMID: 33508514]
[http://dx.doi.org/10.1016/j.celrep.2018.11.084] [PMID: 30566870]
[http://dx.doi.org/10.1038/s41392-020-0155-5] [PMID: 32371956]
[http://dx.doi.org/10.1073/pnas.0908099107] [PMID: 20018762]
[http://dx.doi.org/10.1016/j.molcel.2020.04.017] [PMID: 32559424]
[http://dx.doi.org/10.3390/cells9020432] [PMID: 32059571]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3082] [PMID: 29531160]
[http://dx.doi.org/10.1016/j.canlet.2017.09.020] [PMID: 28947137]
[http://dx.doi.org/10.1038/s41388-020-01514-6] [PMID: 33067576]
[http://dx.doi.org/10.3390/biomedicines8110451] [PMID: 33114428]
[http://dx.doi.org/10.1007/s00432-020-03179-w] [PMID: 32152662]
[http://dx.doi.org/10.3892/ol.2021.12947] [PMID: 34434285]
[http://dx.doi.org/10.1155/2021/6650791] [PMID: 34189138]
[http://dx.doi.org/10.1038/s41589-020-0602-1] [PMID: 32778841]
[http://dx.doi.org/10.1152/ajpcell.00502.2020] [PMID: 33296287]
[http://dx.doi.org/10.1073/pnas.2005976117] [PMID: 32801213]
[http://dx.doi.org/10.1016/j.semcdb.2019.01.009] [PMID: 30658153]
[http://dx.doi.org/10.7554/eLife.59686] [PMID: 32914752]
[http://dx.doi.org/10.1002/iub.2407] [PMID: 33179373]
[http://dx.doi.org/10.1111/j.1365-2184.2008.00579.x] [PMID: 19222485]
[http://dx.doi.org/10.1186/s12957-022-02667-2] [PMID: 35729567]
[http://dx.doi.org/10.3390/cancers13112850] [PMID: 34200480]
[http://dx.doi.org/10.18632/aging.103229] [PMID: 32436862]
[http://dx.doi.org/10.7150/ijbs.42019] [PMID: 32210729]
[http://dx.doi.org/10.1016/j.bbrc.2021.04.104] [PMID: 33971568]
[http://dx.doi.org/10.3390/ijms22052537] [PMID: 33802591]
[http://dx.doi.org/10.1186/s13045-020-00990-3] [PMID: 33276800]
![Wayfinder Image](/images/wayfinder.jpg)