MBOAT1 Promotes Glioma Progression Through Enhancing Ferroptosis Resistance and Immunosuppressive Microenvironment

TL;DR

This study shows that MBOAT1 helps glioma tumors grow by making them resistant to a type of cell death called ferroptosis and by creating an environment that suppresses the immune system.

Contribution

The study identifies MBOAT1 as a novel driver of glioma progression through ferroptosis resistance and immunosuppression.

Findings

MBOAT1 expression is elevated in glioma and linked to poor prognosis.

MBOAT1 promotes ferroptosis resistance and an immunosuppressive tumor microenvironment.

Overexpression of MBOAT1 enhances glioblastoma cell proliferation and migration.

Abstract

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.

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.

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.

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.

Integrating bulk and single‐cell RNA sequencing with functional experiments, we identify MBOAT1 as a key oncogenic driver in glioma. Our findings demonstrate that it promotes tumor progression by conferring resistance to ferroptosis and fostering an immunosuppressive microenvironment, thereby nominating it as a promising therapeutic target.

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