ArticleMolecular cancer research : MCR2008
DNA methylation represses IFN-gamma-induced and signal transducer and activator of transcription 1-mediated IFN regulatory factor 8 activation in colon carcinoma cells.
Article in Molecular cancer research : MCR, 2008. 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, 58 citations in OpenAlex.
- Trial
- A proposed convergent molecular chain linking senescence, cancer, and chronic infection to a correctable failure of dendritic cell instruction.Frontiers in immunology · 2026Review
- Article
- Nuclear glycine decarboxylase suppresses STAT1-dependent MHC-I and promotes cancer immune evasion.The EMBO journal · 2025Article
- Targeting the poliovirus receptor to activate T cells and induce myeloid-derived suppressor cells to differentiate to pro-inflammatory macrophages via the IFN-γ-p-STAT1-IRF8 axis in cancer therapy.Cell death and differentiation · 2025Article
- Article
- Silencing of IRF8 Mediated by m6A Modification Promotes the Progression of T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum.Frontiers in immunology · 2023Article
- Article
- Review
- Review
- DNMT1 constrains IFNβ-mediated anti-tumor immunity and PD-L1 expression to reduce the efficacy of radiotherapy and immunotherapy.Oncoimmunology · 2021Article
- Simultaneous silencing Aurora-A and UHRF1 inhibits colorectal cancer cell growth through regulating expression of DNMT1 and STAT1.International journal of medical sciences · 2021Article
- Loss of a Negative Feedback Loop between IRF8 and AR Promotes Prostate Cancer Growth and Enzalutamide Resistance.Cancer research · 2020Article
- 5-Azacytidine Potentiates Anti-tumor Immunity in a Model of Pancreatic Ductal Adenocarcinoma.Frontiers in immunology · 2020Article
- Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis.Cell reports · 2018Article
- An osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion.The Journal of clinical investigation · 2018Article
- The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.BMC systems biology · 2018Article
- DNA methylation protects against cisplatin-induced kidney injury by regulating specific genes, including interferon regulatory factor 8.Kidney international · 2017Article
- Quantitative specificity of STAT1 and several variants.Nucleic acids research · 2017Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
IFN regulatory factor 8 (IRF8) is both constitutively expressed and IFN-gamma inducible in hematopoietic and nonhematopoietic cells. We have shown that IRF8 expression is silenced by DNA methylation in human colon carcinoma cells, but the molecular mechanism underlying methylation-dependent IRF8 silencing remains elusive. In this study, we observed that IRF8 protein level is inversely correlated with the methylation status of the IRF8 promoter and the metastatic phenotype in human colorectal carcinoma specimens in vivo. Demethylation treatment or knocking down DNMT1 and DNMT3b expression rendered the tumor cells responsive to IFN-gamma to activate IRF8 transcription in vitro. Bisulfite genomic DNA sequencing revealed that the entire CpG island of the IRF8 promoter is methylated. Electrophoresis mobility shift assay revealed that DNA methylation does not directly inhibit IFN-gamma-activated phosphorylated signal transducer and activator of transcription 1 (pSTAT1) binding to the IFN-gamma activation site element in the IRF8 promoter in vitro. Chromatin immunoprecipitation assay revealed that pSTAT1 is associated with the IFN-gamma activation site element of the IRF8 promoter in vivo regardless of the methylation status of the IRF8 promoter. However, DNA methylation results in preferential association of PIAS1, a potent inhibitor of pSTAT1, with pSTAT1 in the methylated IRF8 promoter region. Silencing methyl-CpG binding domain protein 1 (MBD1) expression resulted in IRF8 activation by IFN-gamma in human colon carcinoma cells with methylated IRF8 promoter. Our data thus suggest that human colon carcinoma cells silence IFN-gamma-activated IRF8 expression through MBD1-dependent and PIAS1-mediated inhibition of pSTAT1 function at the methylated IRF8 promoter.
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