MUL1, an Immune Chemokine-Related Gene, Regulates Glioma Cell Proliferation and Migration: Insights from Functional and Mechanistic Studies

Background Glioma is the most common and lethal type of brain tumor, characterized by poor prognosis and high recurrence rates. Immune dysfunction and inflammatory infiltration within the tumor microenvironment (TME) are two hallmarks of glioma. The complex and dynamic interactions between tumor cells and the surrounding microenvironment can create an immunosuppressive TME, accelerating malignant progression. Therefore, investigating the relationship between inflammatory infiltration and immunosuppressive TME, as well as identifying novel biomarkers for glioma prognosis, is critical. Methods We screened samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The CGGA dataset served as the training cohort, while the TCGA dataset was used as the validation cohort. Prognosis-related immune chemokine genes were identified using LASSO-Cox regression analysis. Clinical correlation analysis, Kaplan-Meier survival analysis, and immune checkpoint gene correlation analysis were performed to infer immune infiltration features. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict potential biological functions. Immune infiltration levels were assessed via ESTIMATE and CIBERSORT algorithms. A nomogram risk prediction model was constructed. Finally, in vitro experiments using human glioma cell lines (U251 and U87-MG) were conducted to validate the regulatory mechanisms. Results A total of 1,639 samples were included (970 from CGGA and 669 from TCGA). LASSO-Cox regression identified six immune chemokine-related genes with high prognostic value. Pan-cancer analysis and qPCR validation prioritized MUL1 as the key gene. Elevated MUL1 expression correlated with advanced clinicopathological features (mesenchymal subtype, WHO grade IV), genomic aberrations (1p19q co-deletion, MGMT methylation, IDH mutation), and increased expression of multiple immune checkpoint genes (p < 0.001). High MUL1 expression was also associated with enhanced macrophage infiltration. The nomogram model demonstrated good predictive accuracy (C-index = 0.755 in CGGA, C-index = 0.794 in TCGA). In vitro experiments demonstrated that siRNA-mediated silencing of MUL1 significantly inhibited the viability, migration, and proliferation of two human glioma cell lines (U87-MG and U251) compared to the Control group (P < 0.001). Conclusion This study highlights the biological role of MUL1 in glioma progression and provides novel insights into its regulation of immune cell activation within the TME. These findings offer a theoretical foundation for understanding metabolic molecules in the glioma microenvironment and identifying new therapeutic targets.