ArticleBMC cancer2021
The oncometabolite R-2-hydroxyglutarate dysregulates the differentiation of human mesenchymal stromal cells via inducing DNA hypermethylation.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- The crosstalk between epigenetics and metabolism in the malignant cell.Discover oncology · 2026Review
- The DNA methylation landscape of musculoskeletal sarcomas.Exploration of targeted anti-tumor therapy · 2025Review
- Epitranscriptomic modifications in mesenchymal stem cell differentiation: advances, mechanistic insights, and beyond.Cell death and differentiation · 2024Review
- Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.Frontiers in genetics · 2024Review
- The Role of Epigenetic Modifier Mutations in Peripheral T-Cell Lymphomas.Current issues in molecular biology · 2023Review
- Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities.International journal of molecular sciences · 2023Review
- DNA methylation profile of lip tissue from congenital nonsyndromic cleft lip and palate patients by whole-genome bisulfite sequencing.Birth defects research · 2023Article
- m6A demethylase FTO and osteoporosis: potential therapeutic interventions.Frontiers in cell and developmental biology · 2023Review
- Epigenetic control of mesenchymal stem cells orchestrates bone regeneration.Frontiers in endocrinology · 2023Review
- From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIsocitrate dehydrogenase (IDH1/2) gene mutations are the most frequently observed mutations in cartilaginous tumors. The mutant IDH causes elevation in the levels of R-enantiomer of 2-hydroxylglutarate (R-2HG). Mesenchymal stromal cells (MSCs) are reasonable precursor cell candidates of cartilaginous tumors. This study aimed to investigate the effect of oncometabolite R-2HG on MSCs.
methodsHuman bone marrow MSCs treated with or without R-2HG at concentrations 0.1 to 1.5 mM were used for experiments. Cell Counting Kit-8 was used to detect the proliferation of MSCs. To determine the effects of R-2HG on MSC differentiation, cells were cultured in osteogenic, chondrogenic and adipogenic medium. Specific staining approaches were performed and differentiation-related genes were quantified. Furthermore, DNA methylation status was explored by Illumina array-based arrays. Real-time PCR was applied to examine the signaling component mRNAs involved in.
resultsR-2HG showed no influence on the proliferation of human MSCs. R-2HG blocked osteogenic differentiation, whereas promoted adipogenic differentiation of MSCs in a dose-dependent manner. R-2HG inhibited chondrogenic differentiation of MSCs, but increased the expression of genes related to chondrocyte hypertrophy in a lower concentration (1.0 mM). Moreover, R-2HG induced a pronounced DNA hypermethylation state of MSC. R-2HG also improved promotor methylation of lineage-specific genes during osteogenic and chondrogenic differentiation. In addition, R-2HG induced hypermethylation and decreased the mRNA levels of SHH, GLI1and GLI2, indicating Sonic Hedgehog (Shh) signaling inhibition.
conclusionsThe oncometabolite R-2HG dysregulated the chondrogenic and osteogenic differentiation of MSCs possibly via induction of DNA hypermethylation, improving the role of R-2HG in cartilaginous tumor development.
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