ArticlePloS one2012
Silencing of glutathione peroxidase 3 through DNA hypermethylation is associated with lymph node metastasis in gastric carcinomas.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 66 citations in OpenAlex.
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- Molecular Imprints of Clinical Comorbidities in Hypothalamic Extracellular Vesicles at the Onset of Obesity.ACS omega · 2025Article
- Nanozymes: Innovative Therapeutics in the Battle Against Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
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- Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.Archives of toxicology · 2024Review
- Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines.Biomedicines · 2023Article
- Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review.Antioxidants (Basel, Switzerland) · 2022Review
- Analysis of Influencing Factors on the Occurrence and Development of Gastric Cancer in High-Incidence Areas of Digestive Tract Tumors Based on High Methylation of GPX3 Gene.Journal of oncology · 2022Article
- The antioxidant response in Barrett's tumorigenesis: A double-edged sword.Redox biology · 2021Review
- Proliferation Cycle Transcriptomic Signatures are Strongly associated With Gastric Cancer Patient Survival.Frontiers in cell and developmental biology · 2021Article
- High expression of TREM2 promotes EMT via the PI3K/AKT pathway in gastric cancer: bioinformatics analysis and experimental verification.Journal of Cancer · 2021Article
- Potential relationship between the selenoproteome and cancer.Molecular and clinical oncology · 2020Article
- Reduced Expression of GPX3 in Breast Cancer Patients in Correlation with Clinical Significance.Global medical genetics · 2020Article
- Involvement of glutathione peroxidases in the occurrence and development of breast cancers.Journal of translational medicine · 2020Review
- Article
- Effects of high-fat diet-induced adipokines and cytokines on colorectal cancer development.FEBS open bio · 2019Article
- ROS promote epigenetic remodeling and cardiac dysfunction in offspring following maternal engineered nanomaterial (ENM) exposure.Particle and fibre toxicology · 2019Article
- Gpx3 prevents migration and invasion in gastric cancer by targeting NFкB/Wnt5a/JNK signaling.International journal of clinical and experimental pathology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Gastric cancer remains the second leading cause of cancer-related death in the world. H. pylori infection, a major risk factor for gastric cancer, generates high levels of reactive oxygen species (ROS). Glutathione peroxidase 3 (GPX3), a plasma GPX member and a major scavenger of ROS, catalyzes the reduction of hydrogen peroxide and lipid peroxides by reduced glutathione. To study the expression and gene regulation of GPX3, we examined GPX3 gene expression in 9 gastric cancer cell lines, 108 primary gastric cancer samples and 45 normal gastric mucosa adjacent to cancers using quantitative real-time RT-PCR. Downregulation or silencing of GPX3 was detected in 8 of 9 cancer cell lines, 83% (90/108) gastric cancers samples, as compared to non-tumor adjacent normal gastric samples (P<0.0001). Examination of GPX3 promoter demonstrated DNA hypermethylation (≥ 10% methylation level determined by Bisulfite Pyrosequencing) in 6 of 9 cancer cell lines and 60% of gastric cancer samples (P = 0.007). We also detected a significant loss of DNA copy number of GPX3 in gastric cancers (P<0.001). Treatment of SNU1 and MKN28 cells with 5-Aza-2' Deoxycytidine restored the GPX3 gene expression with a significant demethylation of GPX3 promoter. The downregulation of GPX3 expression and GPX3 promoter hypermethylation were significantly associated with gastric cancer lymph node metastasis (P = 0.018 and P = 0.029, respectively). We also observed downregulation, DNA copy number losses, and promoter hypermethylation of GPX3 in approximately one-third of tumor-adjacent normal gastric tissue samples, suggesting the presence of a field defect in areas near tumor samples. Reconstitution of GPX3 in AGS cells reduced the capacity of cell migration, as measured by scratch wound healing assay. Taken together, the dysfunction of GPX3 in gastric cancer is mediated by genetic and epigenetic alterations, suggesting impairment of mechanisms that regulate ROS and its possible involvement in gastric tumorigenesis and metastasis.
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