Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
Eur Rev Med Pharmacol Sci. 2024 Feb;28(3):1123-1134. doi: 10.26355/eurrev_202402_35349.
DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine (5mC). In general, DNA methylation in cancer is associated with the repression of the expression of tumor suppressor genes (TSG) and the demethylation with the overexpression of oncogenes. DNA methylation was considered a stable modification for a long time, but in 2009, it was reported that DNA methylation is a dynamic modification. The Ten-Eleven-Translocations (TET) enzymes include TET1, TET2, and TET3 and participate in DNA demethylation through the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC). The 5hmC oxidates to 5-formylcytosine (5fC) and 5-carboxylcitosine (5caC), which are replaced by unmodified cytosines via Thymine-DNA Glycosylase (TDG). Several studies have shown that the expression of TET proteins and 5hmC levels are deregulated in gynecological cancers, such as cervical (CC), endometrial (EC), and ovarian (OC) cancers. In addition, the molecular mechanisms involved in this deregulation have been reported, as well as their potential role as biomarkers in these types of cancers. This review shows the state-of-art TET enzymes and the 5hmC epigenetic mark in CC, EC, and OC.
DNA 甲基化是一种涉及将甲基基团转移到胞嘧啶的 C5 位置上以形成 5-甲基胞嘧啶 (5mC) 的表观遗传机制。一般来说，癌症中的 DNA 甲基化与肿瘤抑制基因 (TSG) 的表达抑制有关，而去甲基化与癌基因的过度表达有关。DNA 甲基化曾被认为是一种稳定的修饰，但在 2009 年，据报道 DNA 甲基化是一种动态修饰。Ten-Eleven-Translocations (TET) 酶包括 TET1、TET2 和 TET3，通过将 5mC 氧化为 5-羟甲基胞嘧啶 (5hmC) 来参与 DNA 去甲基化。5hmC 氧化为 5-甲酰基胞嘧啶 (5fC) 和 5-羧基胞嘧啶 (5caC)，它们通过胸腺嘧啶-DNA 糖基化酶 (TDG) 被未修饰的胞嘧啶取代。几项研究表明，TET 蛋白的表达和 5hmC 水平在妇科癌症中失调，如宫颈癌 (CC)、子宫内膜癌 (EC) 和卵巢癌 (OC)。此外，还报道了涉及这种失调的分子机制，以及它们作为这些类型癌症的生物标志物的潜在作用。这篇综述展示了 TET 酶和 5hmC 表观遗传标记在 CC、EC 和 OC 中的最新研究进展。
