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金属硫蛋白1X是一种肿瘤抑制基因,可抑制肾细胞癌中的氧化应激和转移。

Metallothionein 1X is a tumor suppressor gene and inhibits oxidative stress and metastasis in renal cell carcinoma.

作者信息

Rui Rui, Huang Cong, Wu Yucai, Guo Heng, Gong Yanqing, Li Xuesong, Zhou Liqun, He Shiming

机构信息

Department of Urology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng, Beijing, 100034, China.

The Institution of Urology, Peking University, Beijing, 100034, China.

出版信息

Discov Oncol. 2025 Aug 13;16(1):1545. doi: 10.1007/s12672-025-02949-7.

Abstract

Metallothioneins 1X (MT1X) is expressed at low levels in renal cell carcinoma (RCC) and correlates with tumor progression, stage, grade and prognosis, but the mechanism of MT1X's role in renal cell carcinoma is not fully understood at present, and the aim of this study was to investigate the molecular mechanism of MT1X's role in renal cell carcinoma. We used immunofluorescence and flow cytometry to detect intracellular reactive oxygen species (ROS) levels and immunoblotting to detect the expression levels of key proteins of the epithelial-mesenchymal transition (EMT) signaling pathway, transwell assay to assess the cell migration and invasion capacity. It was found that MT1X knockdown significantly upregulated HO-induced intracellular ROS, activated the EMT pathway, and ultimately promoted cell migration and invasion whereas Trolox inhibited cell migration and invasion by suppressing the elevated ROS induced by MT1X knockdown. Here, we reported that MT1X is low-expressed in RCC and that MT1X knockdown promotes cell migration and invasion through the upregulation of intracellular ROS levels, thereby activating the EMT pathway.

摘要

金属硫蛋白1X(MT1X)在肾细胞癌(RCC)中低表达,且与肿瘤进展、分期、分级及预后相关,但目前MT1X在肾细胞癌中作用的机制尚未完全明确,本研究旨在探讨MT1X在肾细胞癌中作用的分子机制。我们采用免疫荧光和流式细胞术检测细胞内活性氧(ROS)水平,免疫印迹法检测上皮-间质转化(EMT)信号通路关键蛋白的表达水平,Transwell实验评估细胞迁移和侵袭能力。结果发现,敲低MT1X显著上调HO诱导的细胞内ROS水平,激活EMT通路,并最终促进细胞迁移和侵袭,而曲洛司坦通过抑制敲低MT1X诱导的ROS升高来抑制细胞迁移和侵袭。在此,我们报道MT1X在RCC中低表达,且敲低MT1X通过上调细胞内ROS水平促进细胞迁移和侵袭,从而激活EMT通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd96/12350890/c1381e934b63/12672_2025_2949_Fig1_HTML.jpg

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