Identification and characterization of mitochondrial E3 ubiquitin protein ligase 1 (MUL1) as an immune chemokine-related prognostic biomarker in glioma

Glioma, the most aggressive primary brain tumor, progresses in close association with an immunosuppressive microenvironment. By integrating the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we identified six immune chemokine-related prognostic genes, with particular focus on mitochondrial E3 ubiquitin protein ligase 1 ( MUL1 ). MUL1 was significantly upregulated in glioma, and its elevated expression correlated with malignant features including isocitrate dehydrogenase (IDH) wild-type status, the aggressive molecular subtypes (including Mesenchymal and Classical), high World Health Organization (WHO) grades, and poor prognosis. This upregulation was also associated with increased immune checkpoint expression and enhanced M2 macrophage infiltration. A nomogram constructed based on MUL1 expression demonstrated relatively reliable prognostic performance. In vitro experiments showed that silencing MUL1 significantly inhibited glioma cell proliferation, migration, and invasion. These findings help clarify the potential role of MUL1 in regulating the immune microenvironment of glioma and provide new evidence supporting its utility as a prognostic biomarker and therapeutic target.