ArticleOncotarget2016
Epigenetic modification of TLR4 promotes activation of NF-κB by regulating methyl-CpG-binding domain protein 2 and Sp1 in gastric cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- Chronic Stress-Induced and Tumor Derived SP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Toll-like receptors in health and disease.MedComm · 2024Review
- Whole-genome bisulfite sequencing reveals the function of DNA methylation in the allotransplantation immunity of pearl oysters.Frontiers in immunology · 2023Article
- Context-dependent functions of pattern recognition receptors in cancer.Nature reviews. Cancer · 2022Review
- Differential Placental DNA Methylation ofFrontiers in pediatrics · 2022Article
- Toll-like receptor 4 methylation grade is linked to depressive symptom severity.Translational psychiatry · 2021Article
- DNA Methylation ofFrontiers in pediatrics · 2021Article
- Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota.International journal of molecular sciences · 2020Article
- MicroRNA-23a-3p Down-Regulation in Active Pulmonary Tuberculosis Patients with High Bacterial Burden Inhibits Mononuclear Cell Function and Phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 Signaling via Targeting IRF1/SP1.International journal of molecular sciences · 2020Article
- USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- 5-Aza-2'-deoxycytidine enhances lipopolysaccharide-induced inflammatory cytokine expression in human dental pulp cells by regulating TRAF6 methylation.Bioengineered · 2019Article
- Curcumin inhibits cell proliferation and migration in NSCLC through a synergistic effect on the TLR4/MyD88 and EGFR pathways.Oncology reports · 2019Article
- Article
- Epigenetic regulation of Toll-like receptors and its roles in type 1 diabetes.Journal of molecular medicine (Berlin, Germany) · 2018Review
- Roles of toll-like receptors: From inflammation to lung cancer progression.Biomedical reports · 2018Article
- Article
- Comprehensive assessment of association between TLR4 gene polymorphisms and cancer risk: a systematic meta-analysis.Oncotarget · 2017Article
- Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis.Oncotarget · 2017Article
- A unified model of the hierarchical and stochastic theories of gastric cancer.British journal of cancer · 2017Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 4 (TLR4) is important in promoting the immune response in various cancers. Recently, TLR4 is highly expressed in a stage-dependent manner in gastric cancer, but the regulatory mechanism of TLR4 expression has been not elucidated it. Here, we investigated the mechanism underlying regulation of TLR4 expression through promoter methylation and histone modification between transcriptional regulation and silencing of the TLR4 gene in gastric cancer cells. Chromatin immunoprecipitation was carried out to screen for factors related to TLR4 methylation such as MeCP2, HDAC1, and Sp1 on the TLR4 promoter. Moreover, DNA methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-dC) induced demethylation of the TLR4 promoter and increased H3K4 trimethylation and Sp1 binding to reactivate silenced TLR4. In contrast, although the silence of TLR4 activated H3K9 trimethylation and MeCP2 complex, combined treatment with TLR4 agonist and 5-aza-dC upregulated H3K4 trimethylation and activated with transcription factors as Sp1 and NF-κB. This study demonstrates that recruitment of the MeCP2/HDAC1 repressor complex increases the low levels of TLR4 expression through epigenetic modification of DNA and histones on the TLR4 promoter, but Sp1 activates TLR4 high expression by hypomethylation and NF-κB signaling in gastric cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.