Wang Yu, Qiao Sen, Wang Ping, Li Mi, Ma Xiaozhen, Wang Hongmei, Dong Junhong
School of Basic Medical Sciences, Shandong Second Medical University, NO. 7166 Baotong West Street, Weifang, 261053, China.
Assisted Reproduction Center, Northwest Women's and Children's Hospital, No.73 Houzaimen, North Street, Xincheng District, Xi'an, 710003, China.
BMC Cancer. 2025 May 12;25(1):859. doi: 10.1186/s12885-025-14151-7.
Cuproptosis, a novel form of regulatory cell death, was investigated in this study for its effects on cuproptosis-associated proteins during gliomas development, offering novel insights into the mechanism of copper ion-based antitumor drugs.
In the present study, bioinformatics and cellular experiments were employed to investigate cuproptosis-related genes (CRGs) in glioma, with a specific focus on SLC31A1.
The study findings indicated that many CRGs (SLC31A1, FDX1, DLST, LIPT1, LIPT2, DLD, NFE2L2, ATP7A, DLAT, GCSH, and ATP7B) were differentially expressed between glioma and non-tumor groups. These genes potentially influence glioma initiation and progression by modulating associated signaling pathways, including those involved in cell cycle regulation, inflammatory responses, and the tumor microenvironment. Survival curve analysis and Cox proportional hazard regression model demonstrated that individuals classified as high-risk exhibited poorer prognosis, suggesting that CRGs possess prognostic capabilities. The assessment of tumor mutational burden indicated that CRGs could serve as biomarkers for predicting the efficacy of immunotherapy in glioma. Further functional analysis of SLC31A1 showed that its elevation was associated with increased glioma cell malignancy, promoting proliferation and migration. Additionally, treatment with the mitotic inhibitor MP-HJ-1b markedly suppressed SLC31A1 expression, consequently inhibiting glioma cell proliferation and migration.
Extensive data analysis indicated that CRGs hold promise as both prognostic markers and potential therapeutic targets for glioma.
本研究对一种新型调节性细胞死亡形式——铜死亡进行了调查，以探究其在神经胶质瘤发展过程中对铜死亡相关蛋白的影响，从而为基于铜离子的抗肿瘤药物作用机制提供新见解。
在本研究中，采用生物信息学和细胞实验来研究神经胶质瘤中与铜死亡相关的基因（CRGs），特别关注SLC31A1。
研究结果表明，许多CRGs（SLC31A1、FDX1、DLST、LIPT1、LIPT2、DLD、NFE2L2、ATP7A、DLAT、GCSH和ATP7B）在神经胶质瘤组和非肿瘤组之间存在差异表达。这些基因可能通过调节相关信号通路影响神经胶质瘤的发生和进展，这些信号通路包括参与细胞周期调控、炎症反应和肿瘤微环境的通路。生存曲线分析和Cox比例风险回归模型表明，被归类为高风险的个体预后较差，这表明CRGs具有预后能力。肿瘤突变负担评估表明，CRGs可作为预测神经胶质瘤免疫治疗疗效的生物标志物。对SLC31A1的进一步功能分析表明，其表达升高与神经胶质瘤细胞恶性程度增加有关，促进细胞增殖和迁移。此外，用有丝分裂抑制剂MP-HJ-1b处理可显著抑制SLC31A1表达，从而抑制神经胶质瘤细胞增殖和迁移。
大量数据分析表明，CRGs有望成为神经胶质瘤的预后标志物和潜在治疗靶点。
