ArticleFrontiers in cell and developmental biology2021
SYVN1-MTR4-MAT2A Signaling Axis Regulates Methionine Metabolism in Glioma Cells.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- MTR4: A Conserved Youth Factor for Vascular Endothelium.Aging cell · 2026Article
- Methionine concentration regulates LSD1 acetylation in glioma cells.Amino acids · 2026Article
- MAT2A enhances PARN transcription via SRF to accelerate glycolysis and drive malignant progression in osteosarcoma.Communications biology · 2026Article
- MTR4 methylation-dependent degradation activates mTORC1 signaling to promote glioma cell survival under methionine starvation.Amino acids · 2025Article
- Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mechanism of CXCL8 regulation of methionine metabolism to promote angiogenesis in gliomas.Discover oncology · 2024Article
- Characterization of methionine dependence in melanoma cells.Molecular omics · 2024Article
- MiR-760 exerts a critical regulatory role in glioma proliferation, migration, and invasion by modulating MMP2 expression.Journal of Cancer · 2024Article
- A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury.Neurochemistry international · 2023Article
- Characterization of methionine dependence in melanoma cells.bioRxiv : the preprint server for biology · 2023Article
- Arylsulfatase D is a prognostic biomarker that promotes glioma cells progression through JAK2/STAT3 pathway and M2 macrophage infiltration.Frontiers in oncology · 2023Article
- A novel prognostic related lncRNA signature associated with amino acid metabolism in glioma.Frontiers in immunology · 2023Article
- Adipocytic Glutamine Synthetase UpregulationFrontiers in oncology · 2021Article
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11 authors at 2 institutions in 1 country.
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Abstract
Methionine is one of the essential amino acids. How tumor cells adapt and adjust their signal transduction networks to avoid apoptosis in a methionine-restricted environment is worthy of further exploration. In this study, we investigated the molecular mechanism of glioma response to methionine restriction, providing a theoretical basis for new treatment strategies for glioma.
methodsWe constructed methionine-restriction-tolerant cells in order to study the response of glioma to a methionine-restricted environment. The transcriptome analysis of the tolerant cells showed significant changes in MAT2A. Western blotting, immunohistochemistry, quantitative real-time PCR, colony formation assays, and other experiments were used to verify the role of MAT2A in glioma genesis. In addition, the regulatory mechanism of MAT2A mRNA nuclear export was investigated by transfection, plasma nucleation separation, and co-immunoprecipitation.
resultsUnder methionine restriction, glioma cells showed high expression of MAT2A, and an inhibitor of MAT2A reduced the proliferation of tumor cells. The expression of MAT2A was positively correlated with World Health Organization-grade glioma. High expression of MAT2A was related to increased transfer of its mRNA out of the nucleus. The expression of nuclear export regulatory molecule MTR4 could affect the export of MAT2A mRNA. In a methionine-restricted environment, ubiquitination of MTR4 was enhanced, and thus its protein level was reduced. The E3 ubiquitin ligase was verified to be SYVN1.
conclusionIn summary, methionine restriction leads to increased ubiquitination of MTR4, which promotes the transfer of MAT2A mRNA out of the nucleus and MAT2A protein expression. MAT2A promotes histone methylation, prompting cells to proliferate in a methionine-restricted environment.
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