关键词: 5-hmC Blood Head and Neck Carcinoma IDH1/2 TET3 Vitamin C α-KG

Mesh : Humans 5-Methylcytosine / analogs & derivatives metabolism Dioxygenases / genetics metabolism Male Epigenesis, Genetic / genetics Female Isocitrate Dehydrogenase / genetics metabolism Middle Aged Head and Neck Neoplasms / genetics blood DNA Methylation / genetics Ascorbic Acid / metabolism blood Adult Proto-Oncogene Proteins / genetics metabolism Gene Expression Regulation, Neoplastic Down-Regulation / genetics Aged Case-Control Studies

来  源:   DOI:10.1007/s11033-024-09714-z

Abstract:
BACKGROUND: Ten-eleven translocases (TETs) are enzymes responsible for demethylation processes, playing a crucial role in maintaining the body\'s methylation balance. Dysregulation of TET expression can lead to abnormal methylation levels. Isocitrate dehydrogenases (IDH) are upstream genes involved in Kreb cycle responsible for production of α-ketoglutarate (α-KG). α-KG and vitamin C are cofactors of TET3 enzyme. There is limited data on the relationship between TET3 and its cofactor Vitamin C in head and neck carcinoma (H&NC).
RESULTS: In this study, we have investigated the expression of the TET3 gene along with IDH1/2 genes involved in the Krebs cycle in the peripheral blood of 32 H&NC patients compared to 32 healthy controls. We estimated serum levels of TET3 protein and vitamin C and 5-hydroxymethylcytosine (5-hmC) percentage in DNA isolated from EDTA blood samples. Our findings revealed that TET3 and IDH1/2 were downregulated in H&NC patients compared to healthy controls. Serum levels of TET3 and Vitamin C were low in H&NC patients compared to healthy controls. Diminished levels of percentage 5-hmC were detected in EDTA blood samples of H&NC patients compared to controls. Spearman correlation analysis revealed a significant positive correlation between TET3 levels, vitamin C levels and 5-hmC percentage.
CONCLUSIONS: The low levels of Vitamin C are believed to contribute to decreased activity of the TET3 gene and less conversion of 5-methylcytosine (5-mC) to 5-hmC. Dietary supplementation of Vitamin C may increase TET3 activity.
摘要:
背景:十一种转位酶(TET)是负责去甲基化过程的酶,在维持身体的甲基化平衡中起着至关重要的作用。TET表达失调可导致甲基化水平异常。异柠檬酸脱氢酶(IDH)是参与Kreb循环的上游基因,负责生产α-酮戊二酸(α-KG)。α-KG和维生素C是TET3酶的辅助因子。关于头颈部癌(H&NC)中TET3及其辅因子维生素C之间关系的数据有限。
结果:在这项研究中,我们调查了32例H&NC患者外周血中TET3基因和与Krebs周期相关的IDH1/2基因的表达,并与32例健康对照进行比较.我们估计了从EDTA血液样品中分离的DNA中TET3蛋白和维生素C以及5-羟甲基胞嘧啶(5-hmC)百分比的血清水平。我们的发现表明,与健康对照组相比,H&NC患者的TET3和IDH1/2下调。与健康对照相比,H&NC患者的血清TET3和维生素C水平较低。与对照相比,在H&NC患者的EDTA血液样品中检测到降低的5-hmC百分比水平。Spearman相关分析显示TET3水平之间存在显著正相关,维生素C水平和5-hmC百分比。
结论:低水平的维生素C被认为有助于降低TET3基因的活性和较少的5-甲基胞嘧啶(5-mC)转化为5-hmC。饮食补充维生素C可能会增加TET3活性。
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