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MT1E 在 AML 中的作用:探索调节性细胞死亡和免疫治疗反应的新途径。

MT1E in AML: a gateway to understanding regulatory cell death and immunotherapeutic responses.

机构信息

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.

Qinghai Province Women and Children's Hospital, Xining, Qinghai Province 810000, China.

出版信息

J Leukoc Biol. 2024 Nov 27;116(6):1515-1529. doi: 10.1093/jleuko/qiae151.

Abstract

Regulated cell death (RCD) plays a crucial role in the initiation and progression of tumors, particularly in acute myeloid leukemia (AML). This study investigates the prognostic importance of RCD-related genes in AML and their correlation with immune infiltration. We combined TCGA and GTEx data, analyzing 1,488 RCD-related genes, to develop a predictive model using LASSO regression and survival analysis. The model's accuracy was validated against multiple databases, examining immune cell infiltration, therapy responses, and drug sensitivity among risk groups. RT-qPCR confirmed MT1E expression in AML patients and healthy bone marrow. CCK8 and Transwell assays measured cell proliferation, adhesion, migration, and invasion, while flow cytometry and Western blotting assessed apoptosis and protein expression. We developed a prognostic model using 10 RCD methods, which demonstrated strong predictive ability, showing an inverse correlation between age and risk scores with survival in AML patients. Functional enrichment analysis of the model is linked to immune modulation pathways. RT-qPCR revealed significantly lower MT1E expression in AML vs healthy bone marrow (P < 0.05). Consequently, experiments were designed to assess the function of MT1E overexpression. Findings indicated that MT1E overexpression showed it significantly reduced THP-1 cell proliferation and adhesion (P < 0.001), decreased migration (P < 0.001), and invasiveness (P < 0.05), and increased apoptosis (P < 0.05), with a notable rise in Caspase3 expression. A novel AML RCD risk model was developed, showing promise as a prognostic marker for evaluating outcomes and immune therapy effectiveness. Insights into MT1E's impact on AML cell proliferation and apoptosis open possibilities for improving patient outcomes and devising personalized treatment strategies.

摘要

细胞程序性死亡(RCD)在肿瘤的发生和发展中起着至关重要的作用,尤其是在急性髓细胞白血病(AML)中。本研究探讨了 RCD 相关基因在 AML 中的预后意义及其与免疫浸润的相关性。我们结合 TCGA 和 GTEx 数据,分析了 1488 个 RCD 相关基因,使用 LASSO 回归和生存分析构建了一个预测模型。该模型的准确性在多个数据库中得到了验证,研究了风险组的免疫细胞浸润、治疗反应和药物敏感性。RT-qPCR 证实了 AML 患者和健康骨髓中 MT1E 的表达。CCK8 和 Transwell 测定法分别测量了细胞增殖、黏附、迁移和侵袭,流式细胞术和 Western blot 测定了细胞凋亡和蛋白表达。我们使用 10 种 RCD 方法开发了一个预后模型,该模型具有很强的预测能力,表明 AML 患者的年龄和风险评分与生存呈负相关。模型的功能富集分析与免疫调节途径有关。RT-qPCR 显示 AML 与健康骨髓相比 MT1E 的表达明显降低(P < 0.05)。因此,设计了实验来评估 MT1E 过表达的功能。结果表明,MT1E 过表达显著降低了 THP-1 细胞的增殖和黏附(P < 0.001),减少了迁移(P < 0.001)和侵袭(P < 0.05),并增加了细胞凋亡(P < 0.05),Caspase3 的表达明显升高。开发了一种新的 AML RCD 风险模型,作为评估预后和免疫治疗效果的预后标志物具有潜力。对 MT1E 对 AML 细胞增殖和凋亡的影响的深入了解为改善患者预后和制定个性化治疗策略提供了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386e/11599122/0a0e7eafddc2/qiae151f1.jpg

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