研究动态
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AML 中的 MT1E:了解调节性细胞死亡和免疫治疗反应的门户。

MT1E in AML: A Gateway to Understanding Regulatory Cell Death and Immunotherapeutic Responses.

发表日期:2024 Jun 29
作者: Xin Zhuang, Peng Chen, Kaiqian Yang, Rong Yang, Xiaoying Man, Ruochen Wang, Yifen Shi
来源: Cell Death & Disease

摘要:

调节性细胞死亡(RCD)在肿瘤的发生和进展中起着至关重要的作用,特别是在急性髓系白血病(AML)中。本研究探讨了 RCD 相关基因在 AML 中的预后重要性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,利用 LASSO 回归和生存分析开发了预测模型。该模型的准确性经过多个数据库的验证,检查了风险群体中的免疫细胞浸润、治疗反应和药物敏感性。 RT-qPCR 证实了 AML 患者和健康骨髓中的 MT1E 表达。 CCK8 和 Transwell 检测测量细胞增殖、粘附、迁移和侵袭,而流式细胞术和蛋白质印迹评估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,该模型表现出很强的预测能力,显示年龄和年龄之间存在负相关。 AML 患者的风险评分与生存率。该模型的功能富集分析与免疫调节途径相关。 RT-qPCR 显示 AML 中的 MT1E 表达显着低于健康骨髓 (p<0.05)。因此,我们设计了实验来评估MT1E过表达的功能。结果表明,MT1E过表达显着降低了THP-1细胞的增殖和粘附(p<0.001),降低了迁移性(p<0.001)和侵袭性(p<0.05),细胞凋亡增加(p<0.05),Caspase3 表达显着增加。开发了一种新型 AML RCD 风险模型,有望作为评估结果和免疫治疗有效性的预后标志物。深入了解 MT1E 对 AML 细胞增殖和凋亡的影响,为改善患者治疗结果和设计个性化治疗策略提供了可能性。© 作者 2024。由牛津大学出版社代表白细胞生物学学会出版。
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 1488 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 versus 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.© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.