研究动态
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CD3D启动子的去甲基化诱导免疫细胞浸润并支持睫状黑素瘤的恶性表型。

Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma.

发表日期:2023 Oct
作者: Chao Zhang, Shuai Wu
来源: Cellular & Molecular Immunology

摘要:

DNA甲基化的改变被誉为恶性疾病诊断、预后和预测价值的有希望的靶点。本研究基于表观遗传改变和免疫细胞浸润分析,研究了葡萄膜黑色素瘤(UM)中CD3D甲基化的机制。对TCGA数据库中的UM患者的转录组数据、450K甲基化数据和临床信息进行了生物信息学分析。通过计算UM样本的基质得分和免疫得分来评估基质和免疫细胞浸润。将UM样本分为高和低基质得分以及免疫得分的组别,然后进行差异和富集分析。通过蛋白质相互作用网络构建和相关分析来识别与预后相关的核心基因。生物信息学分析结果通过UM细胞实验得到了验证。基质得分和免疫得分与UM患者的预后显著相关。CD3D、IRF1、CCL3和FN1被识别为受甲基化驱动的核心基因,影响UM患者的预后。CD3D表达与其甲基化呈最高相关性,并与UM发展的四个关键免疫细胞密切相关。UM细胞中CD3D表达低甲基化,且富集表达,而CD3D的沉默抑制了体外UM细胞的增殖、迁移和侵袭。总之,本研究鉴定了UM中CD3D启动子的低甲基化,与UM的免疫细胞浸润相关。© 2023美国实验生物学联合会。
Alterations in DNA methylation in malignant diseases have been heralded as promising targets for diagnostic, prognostic, and predictive values. This study was based on epigenetic alterations and immune cell infiltration analysis to investigate the mechanism of CD3D methylation in uveal melanoma (UM). Bioinformatics analysis was performed on transcriptome data, 450 K methylation data, and clinical information of UM patients from the TCGA database. Stromal and immune cell infiltration was evaluated by calculating the StromalScore and ImmuneScore of UM samples. UM samples were divided into high and low StromalScore and ImmuneScore groups, followed by differential and enrichment analyses. PPI network construction and correlation analysis was used to identify the core prognosis-related genes. The bioinformatics analysis results were confirmed in UM cell experiments. StromalScore and ImmuneScore were significantly associated with the prognosis of UM patients. CD3D, IRF1, CCL3, and FN1 were identified as core genes driven by methylation that affected the prognosis of UM patients. CD3D expression showed the highest correlation with its methylation and was closely related to the four key immune cells in UM development. CD3D was hypomethylated and abundantly expressed in UM cells, while silencing of CD3D inhibited the proliferation, migration, and invasion of UM cells in vitro. In summary, this study identifies hypomethylation of CD3D promoter in UM, which was associated with immune cell infiltration of UM.© 2023 Federation of American Societies for Experimental Biology.