Oncogenic magnesium transporter 1 upregulates programmed death-1-ligand 1 expression and contributes to growth and radioresistance of glioma cells through the ERK/MAPK signaling pathway

Radiotherapy has been established as a major therapeutic modality for glioma, whereas new therapeutic targets are needed to prevent tumor recurrence. This study intends to explore the regulatory role of magnesium transporter 1 (MAGT1) in radiotherapy resistance of glioma through modulating ERK and programmed death-1-ligand 1 (PD-L1). Our bioinformatics analysis identified differentially expressed MAGT1 in glioma, expression of which was subsequently determined in cohort data of TCGA database and microarray dataset as well as glioma cell lines. Artificial modulation of MAGT1, ERK, and PD-L1 expression was performed to examine their effects on glioma cell proliferation and radioresistance, as reflected by MTT and colony formation assays under irradiation. Mouse glioma cells with manipulated MAGT1 and ERK inhibitors were further injected into mice to assess the <i>in vivo</i> tumor formation ability of glioma cells. It was noted that MAGT1 expression was highly expressed in glioma tissues of TCGA data and microarray dataset, which was then validated in glioma cell lines. Ectopic expression of MAGT1 was revealed to promote the proliferation and radioresistance of glioma cells, which was attributed to the MAGT1-mediated activation of the ERK/MAPK signaling pathway. It was illuminated that MAGT1 stimulated PD-L1 expression through the ERK/MAPK pathway and thus facilitated glioma cell growth. Additionally, MAGT1 overexpression accelerated the <i>in vivo</i> tumor formation of glioma cells, while the ERK inhibitor negated its effect. In conclusion, MAGT1 enhances the growth and radioresistance of glioma cells through the ERK/MAPK signaling pathway-mediated upregulation of PD-L1 expression.