TET3 (Tet Methylcytosine Dioxygenase 3)

These findings propose a novel, composition-based epigenetic stratification framework in CC, revealing that MUC1 promoter methylation pattern structure-rather than average methylation level-has prognostic relevance. Our results highlight the potential of pattern-resolved methylation profiling in the development of clinically applicable epigenetic biomarkers.

In murine models, Xu5P supplementation or adopting Xu5P-rich diets synergizes with anti-PD-1 therapy to enhance antitumor immunity. These findings offer insights into the potentiality of dietary interventions for metastatic cancer.

Notably, combined treatment with the HDAC inhibitor SAHA and the ferroptosis inducer Erastin significantly enhances gemcitabine-induced cytotoxicity in lipogenic PDAC cells. These findings uncover a previously unrecognized non-catalytic function of TET3 in sustaining lipid metabolic reprogramming in PDAC. Targeting the TET3/GATA6 axis in combination with ferroptosis and epigenetic modulators offers a promising strategy to overcome therapeutic resistance in aggressive pancreatic cancer.

Moreover, p53 not only promotes cellular senescence in vitro and in vivo but also reciprocally enhances TET3 and 5-hmC levels. These findings underscore the critical role of elevated TET3 and 5-hmC levels in cellular senescence.

In terms of mechanisms, RELA and STATs recruit TET3 to prevent DNMT-mediated DNA methylation, thereby maintaining CpG island hypomethylation in the ICAM1 promoter. Therefore, TF occupancy limits DNA methylation and affects ICAM1 expression in breast cancer.

The efficacy of ADT in prostate cancer is related to the expression of TET3 in TAMs, and TET3 may be a potential therapeutic target for coordinating ADT.

These findings underscore the influence of tamoxifen derivatives on DNA methylation patterns, particularly through modulating TET3 expression, which appears to be contingent on the presence of estrogen receptors. This study highlights the potential of targeting epigenetic modifications for personalized anti-cancer therapy, offering a novel avenue to improve treatment outcomes.

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.

Moreover, the ascorbate level in the plasma of breast cancer patients was decreased with the accompanying increase of sodium-dependent vitamin C transporters (SLC23A1 and SLC23A2). The presented study indicates the role of TET3 in DNA demethylation in breast carcinogenesis.

GTEx analysis suggested that rs828867 G > A was significantly associated with RP11-287D1.4 and POLE4 mRNA expression. Overall, our results revealed that rs828867 G > A in the TET3 gene is significantly associated with predisposition to NB.

We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.

The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development.