Ask about this productRelated genes to: DNMT2 antibody
- Gene:
- TRDMT1 NIH gene
- Name:
- tRNA aspartic acid methyltransferase 1
- Previous symbol:
- DNMT2
- Synonyms:
- RNMT1
- Chromosome:
- 10p13
- Locus Type:
- gene with protein product
- Date approved:
- 1998-05-07
- Date modifiied:
- 2016-10-05
Related products to: DNMT2 antibody
Related articles to: DNMT2 antibody
- Plastic stabilizers (PSs) are chemical additives that are widely used to inhibit the degradation of plastics. However, their safety concerns and potential carcinogenic risks remain unclear. This study employed network toxicology strategies to elucidate the potential toxic effects and underlying molecular mechanisms of representative PSs, including 2,6-di-tert-butylphenol (2,6-DTB), tert-butylhydroquinone (TBHQ), and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV-328) in breast cancer (BC). Herein, we identified 69 potential genes related to PSs exposure and BC, and optimized five core targets: GSK3B, MAPK14, PARP1, PIM1, and TRDMT1, through subsequent LASSO and SVM algorithms. Based on these core genes, we constructed risk score and nomogram models, both of which revealed that high expression of these five core genes predicts poor prognosis in BC patients. Additionally, molecular docking and dynamic simulations indicated high-affinity interactions between PSs and these core targets (binding energies < -5 kcal/mol). Further correlation analysis with prediction analysis of microarray 50 (PAM50) revealed increased expression of all core genes in the basal-like subtype, especially PIM1 and TRDMT1, which also exhibited the highest risk scores. In vitro, PSs transcriptionally upregulated MAPK14, PIM1, and TRDMT1, with STAT3 mediating their transcription. Importantly, cell counting kit-8 and wound healing assays demonstrated that PSs promote BC cell proliferation and migration. Our research re-evaluates the carcinogenic risks of plastic stabilizers and suggests that PSs may enhance breast cancer progression via targets such as MAPK14, PIM1, and TRDMT1. This study introduces a new approach for evaluating the safety of plastic additives and offers novel insights into the toxicological effects of PSs. - Source: PubMed
Publication date: 2026/03/06
Huo XingfaDuan XueqinHuang XiaojuanXue LinyuanZhao LantaoLi YufengZhang XiaochunZhou Na - RNA methylation has emerged as a critical frontier in epitranscriptomics, with 5-methylcytosine (mC) drawing particular attention for its multilayered roles in post-transcriptional gene regulation. Recent studies demonstrate that mC modulates diverse biological processes by stabilizing RNA transcripts, promoting nuclear export, shaping translational efficiency, and orchestrating noncoding RNA function. Analogous to DNA methylation, mC is dynamically reversible and governed by a finely tuned regulatory system composed of "writers" (such as the NSUN family and DNMT2/TRDMT1), "readers" (including YBX1 and ALYREF), and "erasers" (TET enzymes and ALKBH1), which collectively dictate its spatial and temporal distribution. In lung cancer, disruption of this regulatory axis is increasingly recognized as a driver of tumor phenotypic remodeling, metabolic adaptation, and immune evasion. Notably, writer enzymes such as NSUN2, NSUN4, and NSUN6 promote malignant progression by stabilizing oncogenic transcripts, enhancing translation, and rewiring metabolic networks. Meanwhile, reader proteins YBX1 and ALYREF maintain the stability of mC-modified RNAs and activate proliferative and pro-invasive signaling pathways, including PI3K/AKT, mTOR, and Hippo/Wnt. In addition, mC plays a pivotal role in shaping the tumor immune microenvironment and modulating immune checkpoint activity, thereby influencing the responsiveness and resistance of lung cancer to radiotherapy, chemotherapy, targeted therapy, and immunotherapy. - Source: PubMed
Publication date: 2026/01/07
Zhong XiaoyouWang WenjingLv JiajiaFan WeifeiWang Lin - Neuroblastoma is the most common extracranial solid tumour in children, and genetic susceptibility plays a crucial role in its development. The impact of tRNA Dimethyltransferase 1 (TRDMT1), a primary methyltransferase catalysing 5-methylcytosine (m5C) RNA modification, on neuroblastoma susceptibility remains unexplored. We conducted a case-control study involving 402 neuroblastoma patients and 473 controls from Jiangsu, China. TRDMT1 polymorphisms (rs7074891 T>C, rs10904887 T>C and rs2273734 C>T) were genotyped via the TaqMan assay. Logistic regression was used to assess odds ratios (ORs) and 95% confidence intervals (CIs), while stratification analysis and expression quantitative trait locus (eQTL) analysis were used to examine subgroup-specific effects and regulatory impacts. Additionally, clinical correlation analysis and survival analysis were performed on neuroblastoma datasets used to evaluate. The rs7074891 TC/CC genotype reduced neuroblastoma risk (adjusted OR = 0.75, 95% CI = 0.57-0.98, p = 0.036), especially in children aged ≤ 18 months and those with mediastinal-origin tumours. Conversely, the rs10904887 CC (adjusted OR = 1.73, 95% CI = 1.27-2.38, p = 0.0006) and rs2273734 TT genotypes (adjusted OR = 1.80, 95% CI = 1.09-2.97, p = 0.023) were associated with increased risk, with distinct subgroup-specific effects. Combined 1-3 risk genotypes further confirmed increased susceptibility (adjusted OR = 1.81, 95% CI = 1.38-2.37, p < 0.0001), particularly in males and older children. eQTL analysis revealed that the rs7074891 C and rs10904887 C alleles increased TRDMT1 expression, whereas the rs2273734 T allele decreased it. Elevated TRDMT1 expression was correlated with poor prognosis and high-risk clinical features. TRDMT1 polymorphisms are significantly associated with neuroblastoma susceptibility, providing insights into their genetic and epigenetic mechanisms and potential as biomarkers and therapeutic targets. - Source: PubMed
Zhang MengzhenZhang WenliZhou ChunleiChang JiamingLiu JiabinLin LeiZhang XinxinChen LipingHe JingHan Baowei - - Source: PubMed
Publication date: 2025/09/04
Sharma HeenaYadav RadhaSingh DarshikaGoel BhawanaSeshadri VasudevanKapoor SanjayKapoor Meenu - DNMT2 (TRDMT1) is a human RNA methyltransferase implicated in various disease processes. However, small-molecule targeting of DNMT2 remains challenging due to poor selectivity and low cellular availability of known -adenosylhomocysteine (SAH)-derived ligands. In this study, a DNA-encoded library (DEL) screen identified five non-SAH-like chemotypes that selectively bind DNMT2, including three peptidomimetics. Orthogonal assays confirmed target engagement, and X-ray crystallography revealed a previously unknown allosteric binding pocket formed via active site loop rearrangement. Guided by structural insights, the authors optimized a lead compound with a of 3.04 μM that reduces mC levels in MOLM-13 tRNA and synergizes with doxorubicin to impair cell viability. These inhibitors exhibit unprecedented selectivity over other methyltransferases, offering a promising scaffold for future DNMT2-targeting therapeutics. Beyond pharmacological implications, the study provides conceptual advances in understanding allosteric modulation and structural plasticity of DNMT2. - Source: PubMed
Publication date: 2025/08/05
Frey Ariane FSchwan MerlinWeldert Annabelle CKadenbach ValerieKopp JürgenNidoieva ZarinaZimmermann Robert AGleue LukasZimmer CollinJörg MarkoFriedland KristinaHelm MarkSinning IrmgardBarthels Fabian