Ask about this productRelated genes to: DNMT1 Blocking Peptide
- Gene:
- DNMT1 NIH gene
- Name:
- DNA methyltransferase 1
- Previous symbol:
- DNMT
- Synonyms:
- MCMT, CXXC9
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1991-06-04
- Date modifiied:
- 2019-04-23
Related products to: DNMT1 Blocking Peptide
Related articles to: DNMT1 Blocking Peptide
- Prostate cancer, a prevalent malignancy in the male reproductive system, poses significant therapeutic challenges due to the development of resistance to androgen deprivation therapies such as bicalutamide. While current research predominantly focuses on androgen receptor (AR)-dependent mechanisms of resistance, non-AR-dependent pathways remain poorly understood. Here, we report a novel non-AR-dependent mechanism of bicalutamide resistance centered on DUOXA1, a maturation factor for dual oxidases (DUOX) that catalyzes hydrogen peroxide (HO) production. Our analysis of RNA sequencing data from bicalutamide-resistant and sensitive prostate cancer cells revealed DUOXA1 as a significantly downregulated gene in resistant cells. We demonstrate that hypoxia in the prostate cancer microenvironment enhances HIF1α transcriptional activity, leading to increased DNMT1 expression. DNMT1, an epigenetic modifier, mediates the methylation of the DUOXA1 promoter, thereby silencing its expression. This epigenetic silencing of DUOXA1 inhibits ferroptosis, a form of regulated cell death characterized by iron metabolism disruption and lipid peroxidation, thereby promoting bicalutamide resistance. Our findings indicate that DUOXA1 can enhance bicalutamide resistance by promoting ferroptosis through ROS generation. This study not only provides mechanistic insights into the role of DUOXA1 in bicalutamide resistance but also highlights the HIF1α-DNMT1-DUOXA1 axis as a critical regulator of resistance. Our work suggests potential therapeutic strategies to overcome resistance through epigenetic modulation and activation of DUOXA1, offering a novel perspective on the molecular mechanisms of bicalutamide resistance and paving the way for the development of improved treatment approaches for advanced prostate cancer. - Source: PubMed
Publication date: 2026/04/25
Xia ShunyaoSun YanYe ZiwenJia HaixingLiu ZanXiu Youcheng - Hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases relies primarily on DNA-damaging agents whose efficacy depends on sustained cytotoxic exposure. Whether brief treatment can induce durable transcriptional remodeling remains unclear. Mithramycin A (MA) is a GC-rich DNA-binding agent with transcriptional regulatory activity involving chromatin-associated pathways. Here, we investigated the molecular and functional consequences of a single 90-min HIPEC-mimetic MA exposure in colorectal cancer models. RNA sequencing revealed extensive and coordinated transcriptional remodeling, affecting a substantial fraction of expressed genes and producing a response qualitatively distinct from mitomycin C. MA selectively suppressed key chromatin-associated regulatory factors, including DNMT1, JARID2, and HDAC4, while coordinately activating canonical cyclin-dependent kinase inhibitors CDKN1A, CDKN1C, and CDKN2C. Gene set enrichment analysis demonstrated enrichment of G2/M checkpoint pathways and suppression of oncogenic gene networks. These molecular changes translated into sustained inhibition of clonogenic growth and activation of caspase-dependent apoptosis following drug washout, with hyperthermia potentiating apoptotic signaling. Collectively, these findings indicate that brief MA exposure induces selective modulation of chromatin regulators and durable transcriptional reorganization, supporting modulation of chromatin regulatory networks as a potential therapeutic strategy for HIPEC-based colorectal cancer therapy. - Source: PubMed
Publication date: 2026/04/17
Coburn-Flynn OliviaButchy M VirginiaGhanem YazidEmery RobertVerchio VincentKnapp KristenCollier JessicaJethi SahilSpitz Francis RZhang PingElbezanti Weam OthmanHong Young Ki - Di(2-ethylhexyl) phthalate (DEHP) is a widely used industrial plasticizer, raising global concerns due to its potential endocrine-disrupting effects and environmental persistence. Human exposure to DEHP primarily occurs through the ingestion of contaminated food and water, inhalation of airborne particles, and dermal contact with products containing DEHP. Understanding the toxicological mechanisms of DEHP is essential for evaluating its health risks and developing effective strategies to mitigate its adverse effects. In this study, we conducted long-term exposure experiments to DEHP using both an animal model and in vitro system to investigate the complex interplay among DNA methylation, hyperactivation of macroautophagy/autophagy, mitochondrial dysfunction, and lipid accumulation induced by DEHP. The results revealed that DEHP exposure induced the degradation of DNMT1 (DNA methyltransferase 1) by enhancing its interaction with the autophagy-related protein SQSTM1 (sequestosome 1). DNMT1 degradation resulted in decreased methylation of the promoter regions of genes associated with autophagosome formation, subsequently increasing their expression. The resulting demethylation excessively activated autophagy, contributing to mitochondrial dysfunction and lipid accumulation in the liver. This study uncovered a previously unrecognized interplay among hyperactivation of autophagy, mitochondrial dysfunction, and lipid accumulation in the context of DEHP exposure. These findings enhanced our understanding of DEHP's toxicity and underscored concerns about the long-term health effects of environmental pollutants, particularly regarding metabolic diseases. ATG5:autophagy related 5; ATG16L1: autophagy related 16 like 1; BECN1:beclin 1; COX4/COXIV: cytochrome c oxidase subunit 4; BS-seq:bisulfite sequencing; DCFH-DA: 2',7'-dichlorodihydrofluoresceindiacetate; DEHP: di(2-ethylhexyl) phthalate; DNMT1: DNAmethyltransferase 1; DNMT3A: DNA methyltransferase 3A; FABP4: fattyacid binding protein 4; FASN: fatty acid synthase; LPL: lipoproteinlipase; MAP1LC3/LC3: microtubule associated protein1 light chain 3; NAFLD: nonalcoholic fatty liver disease; NR1H3:nuclear receptor subfamily 1 group H member 3; PPARG: peroxisomeproliferator activated receptor gamma; RB1CC1: RB1 induciblecoiled-coil 1; SQSTM1: sequestosome 1; SREBF2: sterol regulatoryelement binding transcription factor 2; VDAC1: voltage dependentanion channel 1. - Source: PubMed
Publication date: 2026/05/06
Yu Si-YuLiu QiaoGu Yao-HuaHan Wen-ZhuoHan Ao-JingXiong JunLi Tian-ZhouHu Qiu-ShuangGang Fang-YingZhao Chen-QianFeng TianTian JianboMiao XiaopingYu Xue-JieXie Neng-BinYuan Bi-Feng - Accumulating evidence demonstrates that the silencing of tumor suppressor genes by aberrant DNA methylation contributes to the initiation and progression of ovarian cancer (OC), while the systemic methylation profile and the key driver methylation events need to be further explored. Here, by analysing public databases and our resources, we identified the hypermethylation of ZNF154 promoter as a key driver of OC malignancy, which was mediated by the DNA methyltransferase complex DNMT1/UHRF1. Using CRISPR/dCas9-TET1CD, a tool for targeted demethylation, we successfully decreased the methylation level of ZNF154 promoter and reactivated ZNF154 expression, which in turn inhibited the proliferation, migration, and invasion of OC cells. Mechanistically, ZNF154 interacted with KAP1 and directly bound to the ROMO1 promoter, transcriptionally repressing ROMO1 expression, thereby reducing MMP2 and phosphorylated ERK to impede OC progression. Clinically, ZNF154 hypermethylation was correlated with its reduced expression and poor prognosis in OC patients. These findings underscore a pivotal role of aberrant ZNF154 methylation in OC pathogenesis and highlight its potential as both a therapeutic target and a prognostic biomarker for OC patients. - Source: PubMed
Publication date: 2026/05/02
Wei MingbiaoXu YuxiaDeng LingWei WeiLing DongyiZhen ShanshanZhou RanCen WenjianZhang XuHuang MayanLi JundongYan ShumeiLi QinDu Ziming - DNA methylation, is catalyzed by DNA methyltransferases (DNMTs), and its aberrant patterns are implicated in thyroid cancer pathogenesis. The study aimed to investigate the association of DNMTs with thyroid cancer and evaluated the effects of sustained demethylating therapy in a cell-based study. DNMTs expressions in thyroid cancer were analyzed using GEO and TCGA datasets. Additionally, 16 paired and three unpaired papillary thyroid carcinoma (PTC) samples from Taipei Medical University (TMU), along with commercial tissue arrays, were analyzed. Furthermore, the effects of the covalent DNMT inhibitor, 5-azacytidine (5-Aza), and the DNMT1-selective inhibitor, GSK-3484862, on cell viability were evaluated in PTC and follicular thyroid carcinoma (FTC) cell lines. DNMT1 and DNMT3A were upregulated in PTC, with DNMT1 expression correlated with the BRAF mutation and lymph node invasion in TCGA data, findings further confirmed in the TMU cohort and tissue arrays. Short-term (24 h) 5-Aza treatment (1 and 5 µM) induced substantial cell death regardless of the DNA methylation status, whereas short-term GSK-3484862 (5 µM) treatment showed minimal cytotoxicity. In contrast, sustained low-dose GSK-3484862 treatment (approximately 1-3 weeks at 2 µM) effectively reduced global DNA methylation and decreased cell viability of TPC-1 and FTC-236 cells through apoptosis, rather than by inhibiting proliferation. In conclusion, DNMT1 overexpression in PTC suggests its involvement in thyroid carcinogenesis. Sustained inhibition of DNMT1 effectively reduced global DNA methylation and promoted apoptosis, highlighting the potential of prolonged DNMT1-targeted therapy. Further in vitro and in vivo studies are warranted to validate these results and elucidate the underlying mechanisms. - Source: PubMed
Cheng Chao-WenFang Wen-FangWang Yuan-HungYang Yea-MeyLin Jiunn-Diann