ArticleMolecular cancer research : MCR2008
Interferon regulatory factors IRF5 and IRF7 inhibit growth and induce senescence in immortal Li-Fraumeni fibroblasts.
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 43 papers.
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43 citing papers in PubMed, 65 citations in OpenAlex.
- Life-span-dependent transcriptional dynamics of the human heart.Science advances · 2026Article
- Senescent-like microglia limit remyelination through the senescence associated secretory phenotype.Nature communications · 2025Article
- Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.Frontiers in immunology · 2025Review
- DNA Damage and Inflammatory Response of p53 Null H358 Non-Small Cell Lung Cancer Cells to X-Ray Exposure Under Chronic Hypoxia.International journal of molecular sciences · 2024Article
- Current insights and future directions of Li-Fraumeni syndrome.Discover oncology · 2024Review
- Article
- Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model.Nature communications · 2024Article
- Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer: a clinical and translational study.Frontiers of medicine · 2024Article
- Role of interferon regulatory factor 5 (IRF5) in tumor progression: Prognostic and therapeutic potential.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis.Cell reports. Medicine · 2023Article
- Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis.Nature communications · 2023Article
- UMAOH Calcium Phosphate Coatings Designed for Drug Delivery: Vancomycin, 5-Fluorouracil, Interferon α-2b Case.Materials (Basel, Switzerland) · 2022Article
- The landscape of human tissue and cell type specific expression and co-regulation of senescence genes.Molecular neurodegeneration · 2022Article
- Comprehensive analysis of cellular senescence-related genes in the prognosis, tumor microenvironment, and immunotherapy/chemotherapy of clear cell renal cell carcinoma.Frontiers in immunology · 2022Article
- IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma.International journal of biological sciences · 2022Article
- Pregnancy exposure to synthetic phenols and placental DNA methylation - An epigenome-wide association study in male infants from the EDEN cohort.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Age-related telomere attrition causes aberrant gene expression in sub-telomeric regions.Aging cell · 2021Article
- Type I interferons and related pathways in cell senescence.Aging cell · 2020Review
- Candesartan Neuroprotection in Rat Primary Neurons Negatively Correlates with Aging and Senescence: a Transcriptomic Analysis.Molecular neurobiology · 2020Article
- Direct Inhibition of IRF-Dependent Transcriptional Regulatory Mechanisms Associated With Disease.Frontiers in immunology · 2019Review
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8 authors at 1 institution in 1 country.
Funding
Abstract
Cellular immortalization is one of the prerequisite steps in carcinogenesis. By gene expression profiling, we have found that genes in the interferon (IFN) pathway were dysregulated during the spontaneous cellular immortalization of fibroblasts from Li-Fraumeni syndrome (LFS) patients with germ-line mutations in p53. IFN signaling pathway genes were down-regulated by epigenetic silencing during immortalization, and some of these same IFN-regulated genes were activated during replicative senescence. Bisulfite sequencing of the promoter regions of two IFN regulatory transcription factors (IRF5 and IRF7) revealed that IRF7, but not IRF5, was epigenetically silenced by methylation of CpG islands in immortal LFS cells. The induction of IRF7 gene by IFNalpha in immortal LFS cells was potentiated by pretreatment with the demethylation agent 5-aza-2'-deoxycytidine. Overexpression of IRF5 and IRF7 revealed that they can act either alone or in tandem to activate other IFN-regulated genes. In addition, they serve to inhibit the proliferation rate and induce a senescence-related phenotype in immortal LFS cells. Furthermore, polyinosinic:polycytidylic acid treatment of the IRF-overexpressing cells showed a more rapid induction of several IFN-regulated genes. We conclude that the epigenetic inactivation of the IFN pathway plays a critical role in cellular immortalization, and the reactivation of IFN-regulated genes by transcription factors IRF5 and/or IRF7 is sufficient to induce cellular senescence. The IFN pathway may provide valuable molecular targets for therapeutic interventions at early stages of cancer development.
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