ArticleMolecular cancer2024
DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Synergistic epigenetic modulation and ferroptosis induction via codelivery of Decitabine and Sorafenib for potent anti-tumor therapy.Drug delivery · 2026Article
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- SUMOylation-Dependent Repression of BIRC7 by DNMT3a Suppresses Papillary Thyroid Carcinoma Progression.Cell biochemistry and function · 2026Article
- DNMT1 methylates E3 ligase FBXO32 to regulate Myc stability and glycolytic reprogramming in diabetic retinopathy associated endothelial cells.Journal of bioenergetics and biomembranes · 2026Article
- COL11A2 Methylation as a Biomarker for Radiosensitivity and Microenvironment Remodelling in Oral Squamous Cell Carcinoma.International dental journal · 2026Article
- Prognostic value of DNA methylation in head and neck cancer: a systematic review and meta-analysis.Translational cancer research · 2026Article
- Single-cell transcriptome analysis reveals DNMT1Journal of translational medicine · 2026Article
- From Environmental Risk to Cancer Stemness: Epigenetic Regulation in Oral Squamous Cell Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Genebody specific epigenomic reprogramming of transcriptome promotes immune evasion in oropharyngeal cancer patients in North-Eastern India.Clinical epigenetics · 2026Article
- Microcystin-LR Triggers Renal Tubular Ferroptosis Through Epigenetic Repression of GPX4: Implications for Environmental Nephrotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- Dissecting the role of epigenetic regulation in oral squamous cell carcinoma microenvironment: mechanisms and therapeutics.Frontiers in immunology · 2026Review
- SNX1 inhibits human ovarian cancer progression via regulation of the cell cycle, apoptosis and migration.Molecular & cellular oncology · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Cancer and Environmental Xenobiotics: Mechanisms, Controversies, and Innovations.Journal of xenobiotics · 2025Review
- DNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis.Cell death & disease · 2025Article
- Post-translational modifications in the oral microenvironment: Stem cell regulation from periodontal regeneration to oral cancer therapy.World journal of stem cells · 2025Review
- Study on Abnormal Angiogenesis in Moyamoya Disease via Mitochondrial D-Loop Methylation.Brain and behavior · 2025Article
- LINE-1 hypomethylation in cell-free DNA of high-grade glioma patients correlates with tissue levels and is associated with reduced DNMT1 and H4K20me3 expression.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy.International journal of oral science · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundThe faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear.
methodsThe shRNA-specific DNMT1 knockdown was employed to target DNMT1 on oral cancer cells in vitro, as was the use of DNMT1 inhibitors. A xenografted OSCC mouse model was established to determine the effect on tumor suppression. High-throughput microarrays of DNA methylation, bulk and single-cell RNA sequencing analysis, multiplex immunohistochemistry, functional sphere formation and protein immunoblotting were utilized to explore the molecular mechanism involved. Analysis of human samples revealed associations between DNMT1 expression, global DNA methylation and collaborative molecular signaling with oral malignant transformation.
resultsWe investigated DNMT1 expression boosted steadily during oral malignant transformation in human samples, and its inhibition considerably minimized the tumorigenicity in vitro and in a xenografted OSCC model. DNMT1 overexpression was accompanied by the accumulation of cancer-specific DNA hypomethylation during oral carcinogenesis; conversely, DNMT1 knockdown caused atypically extensive genome-wide DNA hypomethylation in cancer cells and xenografted tumors. This novel DNMT1-remodeled DNA hypomethylation pattern hampered the dual activation of PI3K-AKT and CDK2-Rb and inactivated GSK3β collaboratively. When treating OSCC mice, targeting DNMT1 achieved greater anticancer efficacy than the PI3K inhibitor, and reduced the toxicity of blood glucose changes caused by the PI3K inhibitor or combination of PI3K and CDK inhibitors as well as adverse insulin feedback.
conclusionsTargeting DNMT1 remodels a novel global DNA hypomethylation pattern to facilitate anticancer efficacy and minimize potential toxic effects via balanced signaling synergia. Our study suggests DNMT1 is a crucial gatekeeper regarding OSCC destiny and treatment outcome.
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