N6-adenosine methyltransferase METTL4 is a potential prognostic biomarker and associates with cell cycle regulation and immune infiltration in glioma.

Background: Molecular typing is the hope for overcoming brain glioma in the future. METTL4 belongs to the MT-A70 family of methyltransferase proteins and mediates N6-adenosine methylation for both RNA and DNA in eukaryotes. METTL4 has recently been identified to participate in tumorigenesis, but the relation between METTL4 and glioma has not been revealed yet. The aim of this study was to identify METTL4 as a potential biomarker and therapeutic target for predicting the prognosis of glioma. Methods: This study assessed the clinical significance and prognostic value of METTL4 in glioma using data from The Cancer Genome Atlas (TCGA) database. Data from TCGA and Chinese Glioma Genome Atlas (CGGA) databases were used for correlation analysis of METTL4, and the genes that were most related to METTL4 were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) networks and functional interactions between proteins were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Key pathways associated with METTL4 were revealed through gene set enrichment analysis (GSEA). The correlation between METTL4 and tumor immune infiltration was investigated by single-sample gene set enrichment analysis (ssGSEA) of TCGA data. Moreover, the expression of METTL4 was detected through Western blotting. Cell cycle regulation and mitochondrial reactive oxygen species (ROS) were measured by flow cytometry. Results: High expression of METTL4 was associated with a poorer prognosis of glioma patients and METTL4 was an independent prognostic factor for overall survival (OS). Differentially expressed gene (DEG) analysis and GSEA revealed that METTL4 was closely related to cell cycle and immune infiltration. Knockdown of METTL4 induced G0/G1 arrest and higher mitochondrial ROS levels, but there was no significant change in the rate of apoptosis. Conclusions: All findings indicated that METTL4 was a potential prognostic biomarker correlated with cell cycle and immune infiltration in glioma.