ArticleOncogene2016
DNA methylation reactivates GAD1 expression in cancer by preventing CTCF-mediated polycomb repressive complex 2 recruitment.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Identification of epigenetic memory candidates associated with gestational age at birth through analysis of methylome and transcriptional data.Scientific reports · 2021Trial
- Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer.Disease markers · 2021Trial
- Gamma-aminobutyric acid affects the tumor microenvironment and angiogenesis, promoting breast cancer progression.CytoJournal · 2026Article
- GABAergic signaling contributes to tumor cell invasion and poor overall survival in colorectal cancer.Oncogene · 2025Article
- Differential regulation of mesoscale chromosome conformations in osteoblasts and osteosarcoma.Genome biology · 2025Article
- Early colorectal cancer diagnosis: A novel methylated stool DNA model enhanced the diagnostic efficiency.United European gastroenterology journal · 2025Article
- The double role of GABAergic system in systemic tumors: an updated review.Frontiers in oncology · 2025Review
- A GAD1 inhibitor suppresses osteosarcoma growth through the Wnt/β-catenin signaling pathway.Heliyon · 2024Article
- miR-4284 Functions as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting Glutamate Decarboxylase 1.Cancers · 2023Article
- Insights into the leveraging of GABAergic signaling in cancer therapy.Cancer medicine · 2023Review
- Article
- CCCTC-Binding Factor Mediates the Transcription of Insulin-Like Growth Factor Binding Protein 5 Through EZH2 in Ulcerative Colitis.Digestive diseases and sciences · 2023Article
- The Long Noncoding RNA Cytoskeleton Regulator RNA (CYTOR)/miRNA-24-3p Axis Facilitates Nasopharyngeal Carcinoma Progression by Modulating GAD1 Expression.Journal of oncology · 2023Article
- Neurotransmitter signaling: a new frontier in colorectal cancer biology and treatment.Oncogene · 2022Review
- DNA Methylation Profiles ofInternational journal of molecular sciences · 2022Article
- Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension.Circulation · 2021Article
- GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors.Oncology letters · 2021Article
- CTCF-silenced miR-137 contributes to EMT and radioresistance in esophageal squamous cell carcinoma.Cancer cell international · 2021Article
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- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Levels of γ-aminobutyric acid (GABA) and glutamic acid decarboxylase 1 (GAD1), the enzyme that synthesizes GABA, are significantly increased in neoplastic tissues. However, the mechanism underlying this increase remains elusive. Instead of silencing gene transcription, we showed that the GAD1 promoter was hypermethylated in both colon and liver cancer cells, leading to the production of high levels of GAD1. GAD1 is a target gene that is silenced by H3K27me3. The key locus responsible for GAD1 reactivation was mapped to a DNA methylation-sensitive CTCF-binding site (CTCF-BS3) within the third intron of GAD1. Chromosome configuration capture (3C) analysis indicated that an intrachromosomal loop was formed by CTCF self-dimerisation in normal cells (CTCF binds to both unmethylated CTCF-BS3 and CTCF-BS2). The CTCF dimer then interacted with suppressor of zeste 12 homologue (SUZ12), which is a domain of Polycomb repressive complex 2 (PRC2), promoting the methylation of H3K27 and the silencing of GAD1 expression. This silencing was shown to be inhibited by DNA methylation in cancer cells. These findings strongly suggest that GAD1 is reactivated by DNA methylation, which provided a model for DNA methylation and the active orchestration of oncogenic gene expression by CTCF in 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.