ArticlePloS one2012
Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers.
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 33 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
33 citing papers in PubMed, 58 citations in OpenAlex.
- Low expression of TOX predicts poor prognosis of patients with breast cancer in the real world: A retrospective study.Heliyon · 2025Article
- Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.PNAS nexus · 2023Article
- TOX regulates T lymphocytes differentiation and its function in tumor.Frontiers in immunology · 2023Review
- Comparative Genomic Hybridization and Transcriptome Sequencing Reveal Genes with Gain in Acute Lymphoblastic Leukemia:Diagnostics (Basel, Switzerland) · 2022Article
- The TOX subfamily: all-round players in the immune system.Clinical and experimental immunology · 2022Review
- Epigenetic Determinants of Racial Disparity in Breast Cancer: Looking beyond Genetic Alterations.Cancers · 2022Review
- Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation.Nature communications · 2021Article
- TOX Acts as a Tumor Suppressor by Inhibiting mTOR Signaling in Colorectal Cancer.Frontiers in immunology · 2021Article
- Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas.Journal of translational medicine · 2020Article
- Identification of novel epigenetic abnormalities as sputum biomarkers for lung cancer risk among smokers and COPD patients.Lung cancer (Amsterdam, Netherlands) · 2020Article
- High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations.PloS one · 2020Article
- Tox4 modulates cell fate reprogramming.Journal of cell science · 2019Article
- Article
- TOX3 is a favorable prognostic indicator and potential immunomodulatory factor in lung adenocarcinoma.Oncology letters · 2019Article
- Genomic signature of parity in the breast of premenopausal women.Breast cancer research : BCR · 2019Article
- Common cancer-driver mutations and their association with abnormally methylated genes in lung adenocarcinoma from never-smokers.Lung cancer (Amsterdam, Netherlands) · 2018Article
- Data mining of pediatric medulloblastoma microarray expression reveals a novel potential subdivision of the Group 4 molecular subgroup.Oncology letters · 2018Article
- Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas.Oncotarget · 2018Article
- Genome-wide analysis of DNA methylation in bronchial washings.Clinical epigenetics · 2018Article
- Identification of novel gene expression signature in lung adenocarcinoma by using next-generation sequencing data and bioinformatics analysis.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.
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Registered trials
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