ArticleThe Journal of clinical investigation2019
Ascorbic acid-induced TET activation mitigates adverse hydroxymethylcytosine loss in renal cell carcinoma.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- The role of diet in renal cell carcinoma incidence: an umbrella review of meta-analyses of observational studies.BMC medicine · 2022Pooled it
- A Comprehensive Review of Vitamin C for Cancer Therapy: Anti-Tumor Mechanisms and Nano-Formulation Strategies.International journal of nanomedicine · 2026Review
- Hypoxia-inducible factors drive miRNA-mediated downregulation ofbioRxiv : the preprint server for biology · 2025Article
- Impact of Epigenetic Mutations in Chronic Myelomonocytic Leukemia.Current hematologic malignancy reports · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation.BMC biology · 2025Article
- Metabolomics for the Identification of Biomarkers in Kidney Diseases.Nanotheranostics · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Ultrasensitive detection of 5-hydroxymethylcytosine in genomic DNA using a graphene-based sensor modified with biotin and gold nanoparticles.Materials today. Bio · 2024Article
- TET3 downregulation and low 5-hydroxymethylcytosine are epigenetic signatures of head and neck carcinoma.Molecular biology reports · 2024Article
- Development of human pancreatic cancer avatars as a model for dynamic immune landscape profiling and personalized therapy.Science advances · 2024Article
- Review
- Development of Novel Epigenetic Anti-Cancer Therapy Targeting TET Proteins.International journal of molecular sciences · 2023Article
- Oxidative Status Determines the Cytotoxicity of Ascorbic Acid in Human Oral Normal and Cancer Cells.International journal of molecular sciences · 2023Article
- Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy.Biomedicines · 2023Review
- Identification of Agents That Ameliorate Hyperphosphatemia-Suppressed Myogenin Expression Involved in the Nrf2/p62 Pathway in C2C12 Skeletal Muscle Cells.International journal of molecular sciences · 2022Article
- Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid.Antioxidants (Basel, Switzerland) · 2022Review
- Ascorbate content of clinical glioma tissues is related to tumour grade and to global levels of 5-hydroxymethyl cytosine.Scientific reports · 2022Article
- High-Dose Vitamin C for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
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28 authors at 5 institutions in 1 country.
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Abstract
Although clear cell renal cell carcinoma (ccRCC) has been shown to result in widespread aberrant cytosine methylation and loss of 5-hydroxymethylcytosine (5hmC), the prognostic impact and therapeutic targeting of this epigenetic aberrancy has not been fully explored. Analysis of 576 primary ccRCC samples demonstrated that loss of 5hmC was strongly associated with aggressive clinicopathologic features and was an independent adverse prognostic factor. Loss of 5hmC also predicted reduced progression-free survival after resection of nonmetastatic disease. The loss of 5hmC in ccRCC was not due to mutational or transcriptional inactivation of ten eleven translocation (TET) enzymes, but to their functional inactivation by l-2-hydroxyglutarate (L2HG), which was overexpressed due to the deletion and underexpression of L2HG dehydrogenase (L2HGDH). Ascorbic acid (AA) reduced methylation and restored genome-wide 5hmC levels via TET activation. Fluorescence quenching of the recombinant TET-2 protein was unaffected by L2HG in the presence of AA. Pharmacologic AA treatment led to reduced growth of ccRCC in vitro and reduced tumor growth in vivo, with increased intratumoral 5hmC. These data demonstrate that reduced 5hmC is associated with reduced survival in ccRCC and provide a preclinical rationale for exploring the therapeutic potential of high-dose AA in ccRCC.
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