Jabbari Keyvan, Khalafizadeh Ali, Sheikhbahaei Mahboubeh, Soltaninejad Hossein, Babashah Sadegh
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14115-154, Iran.
Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Sciences and Technologies, Tarbiat Modares University, Tehran 14115-154, Iran.
Genes Dis. 2025 Jan 4;12(5):101513. doi: 10.1016/j.gendis.2025.101513. eCollection 2025 Sep.
The ten-eleven translocation 1 (TET1) protein, a member of the human α-ketoglutarate-dependent dioxygenase TET family, functions as a 5-methylcytosine hydroxylase with a strong affinity for genomic regions enriched with 5'-CpG-3' dinucleotides, particularly CpG islands. TET1 is critical in initiating DNA demethylation and maintaining a balanced interaction between demethylation and DNA methylation, which is essential for genomic methylation stability and precise epigenetic regulation. By removing methyl groups from specific tumor suppressor genes, TET1 can influence their expression. This review summarizes the latest advancements in TET1 research, emphasizing its role in demethylation mechanisms and its significance in regulatory processes related to clinical conditions. TET1 is a crucial mediator of demethylation, although the precise details of this mechanism are not yet fully understood. Additionally, TET1 plays a key role in inhibiting tumor progression, but its effects vary across different tumors. This variability arises from its interactions with diverse signaling pathways, where it can function either as an antagonist or a promoter. The role of TET1 remains controversial in certain cancer types, and its potential oncogenic functions have attracted growing interest, opening new avenues for investigation.
10-11易位蛋白1（TET1）是人类α-酮戊二酸依赖性双加氧酶TET家族的成员，作为一种5-甲基胞嘧啶羟化酶，对富含5'-CpG-3'二核苷酸的基因组区域，特别是CpG岛具有很强的亲和力。TET1在启动DNA去甲基化以及维持去甲基化与DNA甲基化之间的平衡相互作用方面至关重要，这对于基因组甲基化稳定性和精确的表观遗传调控必不可少。通过从特定的肿瘤抑制基因上去除甲基基团，TET1可以影响它们的表达。本综述总结了TET1研究的最新进展，强调了其在去甲基化机制中的作用及其在与临床病症相关的调控过程中的意义。TET1是去甲基化的关键介质，尽管该机制的确切细节尚未完全了解。此外，TET1在抑制肿瘤进展中起关键作用，但其作用在不同肿瘤中有所不同。这种变异性源于其与多种信号通路的相互作用，在这些信号通路中它既可以作为拮抗剂也可以作为促进剂发挥作用。TET1在某些癌症类型中的作用仍存在争议，其潜在的致癌功能已引起越来越多的关注，为研究开辟了新途径。
