ArticleJournal of experimental & clinical cancer research : CR2013
Aberrant DNA methyltransferase expression in pancreatic ductal adenocarcinoma development and progression.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- Epigenetic modulation to overcome immune suppression in pancreatic cancer.Clinical epigenetics · 2026Review
- Insight into the role of DNA methylation in prognosis and treatment response prediction of gastrointestinal cancers.Epigenomics · 2025Review
- Aberrant DNMT1-mediated DACH1 methylation is associated with colorectal adenoma-to-carcinoma progression.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- EZH2 deletion does not affect acinar regeneration but restricts progression to pancreatic cancer in mice.JCI insight · 2024Article
- Review
- Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges.Frontiers of medicine · 2023Review
- Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Reveals That TAM2-Driven Genes Affect Immunotherapeutic Response and Prognosis in Pancreatic Cancer.International journal of molecular sciences · 2023Article
- Comparative oncology reveals DNMT3B as a molecular vulnerability in undifferentiated pleomorphic sarcoma.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- ITGA2 induces STING expression in pancreatic cancer by inducing DNMT1 degradation.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1.Biomolecules · 2022Review
- Senescence-Associated miRNAs and Their Role in Pancreatic Cancer.Pathology oncology research : POR · 2022Review
- Adenosine Kinase on Deoxyribonucleic Acid Methylation: Adenosine Receptor-Independent Pathway inFrontiers in pharmacology · 2022Review
- Review
- DNA methylation inhibitors: Retrospective and perspective view.Advances in cancer research · 2021Article
- DNMT1 as a therapeutic target in pancreatic cancer: mechanisms and clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy.Cancers · 2020Review
- Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B.Nucleic acids research · 2020Article
- Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAltered gene methylation, regulated by DNA methyltransferases (DNMT) 1, 3a and 3b, contributes to tumorigenesis. However, the role of DNMT in pancreatic ductal adenocarcinoma (PDAC) remains unknown.
methodsExpression of DNMT 1, 3a and 3b was detected in 88 Pancreatic ductal adenocarcinoma (PDAC) and 10 normal tissue samples by immunohistochemistry. Changes in cell viability, cell cycle distribution, and apoptosis of PDAC cell lines (Panc-1 and SW1990) were assessed after transfection with DNMT1 and 3b siRNA. Levels of CDKN1A, Bcl-2 and Bax mRNA were assessed by qRT-PCR, and methylation of the Bax gene promoter was assayed by methylation-specific PCR (MSP).
resultsDNMT1, 3a and 3b proteins were expressed in 46.6%, 23.9%, and 77.3% of PDAC tissues, respectively, but were not expressed in normal pancreatic tissues. There was a co-presence of DNMT3a and DNMT3b expression and an association of DNMT1 expression with alcohol consumption and poor overall survival. Moreover, knockdown of DNMT1 and DNMT3b expression significantly inhibited PDAC cell viability, decreased S-phase but increased G1-phase of the cell cycle, and induced apoptosis. Molecularly, expression of CDKN1A and Bax mRNA was upregulated, and the Bax gene promoter was demethylated. However, a synergistic effect of combined DNMT1 and 3b knockdown was not observed.
conclusionExpression of DNMT1, 3a and 3b proteins is increased in PDAC tissues, and DNMT1 expression is associated with poor prognosis of patients. Knockdown of DNMT1 and 3b expression arrests tumor cells at the G1 phase of the cell cycle and induces apoptosis. The data suggest that DNMT knockdown may be a novel treatment strategy for PDAC.
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