The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.

中文翻译：

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SLC7A11 与错配修复基因表达负相关，并赋予胶质母细胞瘤细胞在低葡萄糖条件下对辐射敏感。

胱氨酸/谷氨酸逆向转运蛋白 xCT (SLC7A11) 在许多癌症中经常上调，包括胶质母细胞瘤 (GBM)。SLC7A11 介导的吸收的胱氨酸被还原为半胱氨酸，这是一种用于谷胱甘肽合成和抗氧化细胞防御的前体氨基酸。然而，关于 SLC7A11 的生物学功能及其对 GBM 治疗反应的影响知之甚少。在这里，我们报告说，与正常脑组织相比，GBM 中 SLC7A11 的表达更高，但在 TCGA 和 CGGA 数据库的生物信息学分析中与肿瘤分级呈负相关，并且对生存产生积极影响。此外，通过 Pearson 相关分析确定了 SLC7A11 与错配修复 (MMR) 基因表达之间的负相关。在葡萄糖限制培养条件下的 GBM 细胞中，SLC7A11 的过表达显着降低了 MMR 基因的表达，包括 MLH1、MSH6 和 EXO1。SLC7A11 过表达的 GBM 细胞表现出双链断裂 (DSB) 水平升高和对放射治疗的敏感性增加。总之，我们的工作表明 SLC7A11 可能是预测 GBM 对放射治疗有更好反应的潜在生物标志物。