Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Department of Otorhinolaryngology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Mol Biol Rep. 2024 Jul 31;51(1):877. doi: 10.1007/s11033-024-09714-z.
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).
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.
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.
十-十一转移酶（TET）是负责去甲基化过程的酶，在维持体内甲基化平衡中起着关键作用。TET 表达的失调会导致异常的甲基化水平。异柠檬酸脱氢酶（IDH）是参与克雷布斯循环的上游基因，负责产生α-酮戊二酸（α-KG）。α-KG 和维生素 C 是 TET3 酶的辅助因子。关于 TET3 及其辅因子维生素 C 在头颈部癌（H&NC）中的关系，数据有限。
在这项研究中，我们研究了 32 例 H&NC 患者与 32 例健康对照者外周血中的 TET3 基因及其参与克雷布斯循环的 IDH1/2 基因的表达。我们估计了 EDTA 抗凝血样中 TET3 蛋白和维生素 C 以及 5-羟甲基胞嘧啶（5-hmC）的血清水平。我们的研究结果显示，与健康对照组相比，TET3 和 IDH1/2 在 H&NC 患者中下调。与健康对照组相比，H&NC 患者的血清 TET3 和维生素 C 水平较低。与对照组相比，H&NC 患者的 EDTA 抗凝血样中 5-hmC 的百分比降低。Spearman 相关分析显示 TET3 水平、维生素 C 水平和 5-hmC 百分比之间存在显著正相关。
维生素 C 水平较低可能导致 TET3 基因活性降低，5-甲基胞嘧啶（5-mC）向 5-hmC 的转化减少。维生素 C 的膳食补充可能会增加 TET3 的活性。
