ArticleNeuro-oncology2014
Lactate dehydrogenase A silencing in IDH mutant gliomas.
Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- Metabolic modulation of glioblastoma by dietary intervention: a systematic review.Journal of neuro-oncology · 2026Pooled it
- A relative methylation ordering biomarker of lactylation-related genes predicts prognosis and therapeutic response in cutaneous melanoma.Epigenetics · 2026Article
- Intensification versus combination: revisiting the past and envisioning the future of LDHA inhibitors.Cancer chemotherapy and pharmacology · 2026Review
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- 1p/19q codeletion induces targetable and imageable vulnerabilities in glucose metabolism in oligodendrogliomas.Neuro-oncology · 2026Article
- Review
- Metabolic Landscape and Emerging Therapeutic Potential in Pediatric and Adult Gliomas.International journal of molecular sciences · 2026Review
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Cell-Free DNA (cfDNA), Its Applications in Cancer Diagnosis and Monitoring, and Its Potential Role in Regulating Cancer Metabolism.Advances in experimental medicine and biology · 2026Review
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- Nano-Based Technology in Glioblastoma.Molecules (Basel, Switzerland) · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer.Journal of bioenergetics and biomembranes · 2025Review
- Mechanism analysis and targeted therapy of IDH gene mutation in glioma.American journal of cancer research · 2025Review
- Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma.BMC medicine · 2024Review
- Review
- Metabolism: an important player in glioma survival and development.Discover oncology · 2024Review
- A patient-derived cell model for malignant transformation in IDH-mutant glioma.Acta neuropathologica communications · 2024Article
- D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells.Haematologica · 2024Article
- A negative feedback loop underlies the Warburg effect.NPJ systems biology and applications · 2024Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMutations of the isocitrate dehydrogenase 1 and 2 gene (IDH1/2) were initially thought to enhance cancer cell survival and proliferation by promoting the Warburg effect. However, recent experimental data have shown that production of 2-hydroxyglutarate by IDH mutant cells promotes hypoxia-inducible factor (HIF)1α degradation and, by doing so, may have unexpected metabolic effects.
methodsWe used human glioma tissues and derived brain tumor stem cells (BTSCs) to study the expression of HIF1α target genes in IDH mutant ((mt)) and IDH wild-type ((wt)) tumors. Focusing thereafter on the major glycolytic enzyme, lactate dehydrogenase A (LDHA), we used standard molecular methods and pyrosequencing-based DNA methylation analysis to identify mechanisms by which LDHA expression was regulated in human gliomas.
resultsWe found that HIF1α-responsive genes, including many essential for glycolysis (SLC2A1, PDK1, LDHA, SLC16A3), were underexpressed in IDH(mt) gliomas and/or derived BTSCs. We then demonstrated that LDHA was silenced in IDH(mt) derived BTSCs, including those that did not retain the mutant IDH1 allele (mIDH(wt)), matched BTSC xenografts, and parental glioma tissues. Silencing of LDHA was associated with increased methylation of the LDHA promoter, as was ectopic expression of mutant IDH1 in immortalized human astrocytes. Furthermore, in a search of The Cancer Genome Atlas, we found low expression and high methylation of LDHA in IDH(mt) glioblastomas.
conclusionTo our knowledge, this is the first demonstration of downregulation of LDHA in cancer. Although unexpected findings, silencing of LDHA and downregulation of several other glycolysis essential genes raise the intriguing possibility that IDH(mt) gliomas have limited glycolytic capacity, which may contribute to their slow growth and better prognosis.
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