ABSTRACT Background Emerging evidence indicates that ferroptosis characterized by lipid peroxidation is becoming a promising therapeutic strategy in glioma. However, the role of the MBOAT family, key regulators of membrane phospholipids remodeling in ferroptosis, remains unexplored in glioma. Methods We systematically analyzed the expression and clinical significance of MBOAT1 in glioma using TCGA, CGGA, GEO, and GTEx databases. Functional mechanisms were investigated through enrichment, single‐cell RNA sequencing, and immune infiltration analyses. We experimentally validated the oncogenic role of MBOAT1 in GBM through both in vivo and in vitro experiments. Results MBOAT1 expression was elevated in glioma and correlated with increased grades and poor patient prognosis. Cox regression analysis identified MBOAT1 as an independent prognostic factor. Functional enrichment analysis and single cell RNA‐seq analysis revealed that MBOAT1 is associated with enhanced ferroptosis resistance. Furthermore, the immune infiltration analysis and cell communication analysis suggested that MBOAT1 promotes an immunosuppressive microenvironment. Experiments confirmed that overexpression of MBOAT1 promoted GBM cell proliferation, migration, invasion, and ferroptosis resistance, while its knockdown had the opposite effect. Conclusion Our findings suggest that MBOAT1 promotes glioma progression by mediating ferroptosis resistance and is related to an immunosuppressive microenvironment, highlighting its potential as an independent prognostic biomarker and a promising therapeutic target.
Fan et al. (Sun,) studied this question.