ArticleCancer science2010
DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- 6-Methoxydihydrosanguinarine exhibits cytotoxicity and sensitizes TRAIL-induced apoptosis of hepatocellular carcinoma cells through ROS-mediated upregulation of DR5.Medical oncology (Northwood, London, England) · 2023Article
- Epigenetic Deregulation of Apoptosis in Cancers.Cancers · 2021Review
- The fungal metabolite chaetocin is a sensitizer for pro-apoptotic therapies in glioblastoma.Cell death & disease · 2019Article
- Review
- DNMT3a promotes proliferation by activating the STAT3 signaling pathway and depressing apoptosis in pancreatic cancer.Cancer management and research · 2019Article
- The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma.Journal of cellular physiology · 2018Review
- Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.Nature communications · 2016Article
- Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development.Biochemical and biophysical research communications · 2015Article
- Hepatocellular carcinoma: targeting of oncogenic signaling networks in TRAIL resistant cancer cells.Molecular biology reports · 2014Review
- Aza-deoxycytidine induces apoptosis or differentiation via DNMT3B and targets embryonal carcinoma cells but not their differentiated derivatives.British journal of cancer · 2014Article
- Exposure to Penicillium mycotoxins alters gene expression of enzymes involved in the epigenetic regulation of bovine macrophages (BoMacs).Mycotoxin research · 2013Article
- Article
- Down-regulation of DNA methyltransferase 3B in staurosporine-induced apoptosis and its mechanism in human hepatocarcinoma cell lines.Molecular and cellular biochemistry · 2013Article
- MicroRNA-148b enhances the radiosensitivity of non-Hodgkin's Lymphoma cells by promoting radiation-induced apoptosis.Journal of radiation research · 2012Article
- A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase.Cancers · 2012Article
- DNA methylation profiling across the spectrum of HPV-associated anal squamous neoplasia.PloS one · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation plays a critical role in chromatin remodeling and gene expression. DNA methyltransferases (DNMTs) are hypothesized to mediate cellular DNA methylation status and gene expression during mammalian development and in malignant diseases. In this study, we examined the role of DNA methyltransferase 1 (DNMT1) and DNMT3b in cell proliferation and survival of hepatocellular carcinoma (HCC) cells. Gene silencing of both DNMT1 and DNMT3b by targeted siRNA knockdown reduces cell proliferation and sensitizes the cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death. The proapoptotic protein caspase-8 demonstrated promoter hypermethylation in HCC cells and was up-regulated by knockdown of DNMT1 and DNMT3b both at mRNA and protein levels. In addition, death receptor TRAIL-R2/DR5 (TRAIL receptor 2/death receptor 5) did not exhibit promoter hypermethylation in HCC cells but was also up-regulated by knockdown of DNMT1 and DNMT3b both at mRNA and protein levels. Consistent with this observation, the combined transfection of DNMT1-siRNA plus DNMT3b-siRNA enhanced formation of the TRAIL-death-inducing signaling complex formation in HCC cells. In conclusion, our data suggest that DNA methylation of specific genomic regions maintained by DNMT1 and DNMT3b plays a critical role in survival of HCC cells, and a simultaneous knockdown of both DNMT1 and DNMT3b may be a novel anticancer strategy for the treatment of HCC.
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