MICAL1 促进急性髓系白血病的增殖,并与临床预后和免疫浸润相关。
MICAL1 promotes the proliferation in acute myeloid leukemia and is associated with clinical prognosis and immune infiltration.
发表日期:2024 Jul 12
作者:
Yinsen Song, Zhenzhen Yang, Na Gao, Bojun Zhang
来源:
GENES & DEVELOPMENT
摘要:
急性髓系白血病(AML)是最常见的造血系统恶性肿瘤之一,预后差,复发率高。代谢失调在 AML 进展中发挥着重要作用。本研究旨在利用 TCGA 和 GEO 数据集对 MRG 进行全面分析,并进一步探讨关键 MRG 在 AML 进展中的潜在功能。在这项研究中,我们使用 TCGA 和 GEO 数据集鉴定了 AML 中 17 个与生存相关的差异表达 MRG。使用 17 个 MRG 将 150 个 AML 样本分为三个分子亚型,我们发现三个分子亚型与铁死亡、铜死亡和 m6A 相关基因表现出不同的关联。此外,通过 LASSO-Cox 逐步回归分析建立了包含 9 个 MRG 且具有良好预测能力的预后特征。在 17 个 MRG 中,我们的注意力集中在 MICAL1,它在包括 AML 在内的多种肿瘤中高表达,并且在多种 AML 细胞系中也证实了其过度表达。我们还发现 MICAL1 的表达与多种免疫细胞相关。此外,功能实验表明,MICAL1 的敲低可明显抑制 AML 细胞的增殖。总体而言,这项研究不仅有助于更深入地了解 AML 的分子机制,而且为 AML 治疗提供了潜在的靶点和预后标志物。这些发现为进一步研究 AML 相关的治疗策略和机制提供了强有力的支持,有可能改善 AML 患者的预后和生活质量。然而,还需要进一步的研究来验证这些发现并探索更深入的分子机制。© 2024。作者。
Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular subtypes exhibited a different association with ferroptosis, cuproptosis and m6A related genes. Moreover, a prognostic signature that comprised nine MRGs and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. Among the 17 MRGs, our attention focused on MICAL1 which was highly expressed in many types of tumors, including AML and its overexpression was also confirmed in several AML cell lines. We also found that the expression of MICAL1 was associated with several immune cells. Moreover, functional experiments revealed that knockdown of MICAL1 distinctly suppressed the proliferation of AML cells. Overall, this study not only contributes to a deeper understanding of the molecular mechanisms underlying AML but also provides potential targets and prognostic markers for AML treatment. These findings offer robust support for further research into therapeutic strategies and mechanisms related to AML, with the potential to improve the prognosis and quality of life for AML patients. Nevertheless, further research is needed to validate these findings and explore more in-depth molecular mechanisms.© 2024. The Author(s).