ArticleOncogene2018
DNA methyltransferase 3A isoform b contributes to repressing E-cadherin through cooperation of DNA methylation and H3K27/H3K9 methylation in EMT-related metastasis of gastric cancer.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics.Nutrients · 2022Pooled it
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- RNA 5-Methylcytosine Modification in Myocardial Fibrosis.Reviews in cardiovascular medicine · 2025Review
- Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle.Cell death & disease · 2025Article
- Hypoxia-induced genome-wide DNA demethylation by DNMT3A and EMT of cancer cells.Cellular & molecular biology letters · 2025Article
- Overexpression of miR-328-3p Inhibits Epithelial-Mesenchymal Transition in Prostate Cancer by Downregulating PFN1.Applied biochemistry and biotechnology · 2025Article
- DNMT3A Cooperates with YAP/TAZ to Drive Gallbladder Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Upregulation of E-cadherin by the combination of methionine restriction and HDAC2 intervention for inhibiting gastric carcinoma metastasis.Acta biochimica et biophysica Sinica · 2024Article
- Therapeutic vulnerabilities of cancer stem cells and effects of natural products.Natural product reports · 2023Review
- RNF2 inhibits E-Cadherin transcription to promote hepatocellular carcinoma metastasis via inducing histone mono-ubiquitination.Cell death & disease · 2023Article
- DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.Clinical and translational radiation oncology · 2023Article
- Role of epithelial-mesenchymal transition factor SNAI1 and its targets in ovarian cancer aggressiveness.Journal of cancer metastasis and treatment · 2023Article
- KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11.Open medicine (Warsaw, Poland) · 2023Article
- Relationship between Epithelial-to-Mesenchymal Transition and Tumor-Associated Macrophages in Colorectal Liver Metastases.International journal of molecular sciences · 2022Review
- The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.Journal of the National Cancer Center · 2022Review
- Low mitochondrial DNA copy number induces chemotherapy resistance via epithelial-mesenchymal transition by DNA methylation in esophageal squamous cancer cells.Journal of translational medicine · 2022Article
- Demethylation of H3K9 and H3K27 Contributes to the Tubular Renal Damage Triggered by Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Epigenetic modification regulates tumor progression and metastasis through EMT (Review).International journal of oncology · 2022Review
- Calreticulin enhances gastric cancer metastasis by dimethylating H3K9 in the E-cadherin promoter region mediating by G9a.Oncogenesis · 2022Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methyltransferase 3A (DNMT3A) has been recognised as a key element of epigenetic regulation in normal development, and the aberrant regulation of DNMT3A is implicated in multiple types of cancers, especially haematological malignancies. However, its clinical significance and detailed functional role in solid tumours remain unknown, although abnormal expression has gained widespread attention in these cancers. Here, we show that DNMT3A isoform b (DNMT3Ab), a member of the DNMT3A isoform family, is critical for directing epithelial-mesenchymal transition (EMT)-associated metastasis in gastric cancer (GC). DNMT3Ab is positively linked to tumour-node-metastasis (TNM) stage, lymph node metastasis and poor prognosis in GC patients. Overexpression of DNMT3Ab promotes GC cell migration and invasion as well as EMT through repression of E-cadherin. Meanwhile, DNMT3Ab promotes lung metastasis of GC in vivo. Mechanistic studies indicate that DNMT3Ab mediates the epigenetic inaction of the E-cadherin gene via DNA hypermethylation and histone modifications of H3K9me2 and H3K27me3. Depletion of DNMT3Ab effectively restores the expression of E-cadherin and reverses TGF-β-induced EMT by reducing DNA methylation, H3K9me2 and H3K27me3 levels at the E-cadherin promoter. Importantly, DNMT3Ab cooperated with H3K9me2 and H3K27me3 contributes to the transcriptional regulation of E-cadherin in a Snail-dependent manner. Further, gene expression profiling analysis indicates that multiple metastasis-associated genes and oncogenic signalling pathways are regulated in response to DNMT3Ab overexpression. These results identify DNMT3Ab as a crucial regulator of metastasis-related genes in GC. Targeting the DNMT3Ab/Snail/E-cadherin axis may provide a promising therapeutic strategy in the treatment of metastatic GC with high DNMT3Ab expression.
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