SYVN1-MTR4-MAT2A Signaling Axis Regulates Methionine Metabolism in Glioma Cells
Methionine is among the essential proteins. How tumor cells change and adjust their signal transduction systems to prevent apoptosis inside a methionine-restricted atmosphere deserves further exploration. Within this study, we investigated the molecular mechanism of glioma reaction to methionine restriction, supplying a theoretical grounds for new treatment techniques for glioma.
Methods: We built methionine-restriction-tolerant cells to be able to read the response of glioma to some methionine-restricted atmosphere. The transcriptome research into the tolerant cells demonstrated significant alterations in MAT2A. Western blotting, immunohistochemistry, quantitative real-time PCR, colony formation assays, along with other experiments were utilised to ensure the function of MAT2A in glioma genesis. Additionally, the regulatory mechanism of MAT2A mRNA nuclear export was investigated by transfection, plasma nucleation separation, and co-immunoprecipitation.
Results: Under methionine restriction, glioma cells demonstrated high expression of MAT2A, as well as 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 associated with elevated change in its mRNA from the nucleus. The expression of nuclear export regulatory molecule MTR4 may affect the export of MAT2A mRNA. Inside a methionine-restricted atmosphere, ubiquitination of MTR4 was enhanced, and therefore its protein level was reduced. The E3 ubiquitin ligase was verified to become SYVN1.
Conclusion: In conclusion, methionine restriction results in elevated ubiquitination of MTR4, which promotes the change in MAT2A mRNA from the nucleus and MAT2A protein expression. MAT2A promotes histone methylation,PF-9366 prompting cells to proliferate inside a methionine-restricted atmosphere.