METTL2B m3C RNA transferase: oncogenic role in ovarian cancer progression via regulation of the mTOR/AKT pathway and its link to the tumor immune microenvironment

Abstract

Abstract Background Aberrant expression of N3-methylcytidine methyltransferase 2B (METTL2B) has been observed in various human malignancies, including those of the prostate, liver, breasts, and bladder. However, its role in ovarian cancer (OC) remains largely unexplored. This research preliminarily investigated METTL2B expression in OC and elucidated the associated molecular mechanisms. Methods We utilized three publicly available cancer-related databases (Genotype-Tissue Expression, Gene Expression Omnibus, and The Cancer Genome Atlas) to identify gene signatures in patients with OC and normal individuals with a specific focus on METTL2B. The role of METTL2B in OC was evaluated using patient survival data, and its impact on oncogenic behaviors in both cell and animal models, including growth potential, migration, invasion, and the tumor microenvironment, was examined. This assessment was conducted using bioinformatics tools such as Gene Set Cancer Analysis, GeneMANIA, and Tumor Immune Single-cell Hub 2. Additionally, the association between drug sensitivity and METTL2B expression was analyzed using CellMiner. Results METTL2B expression was significantly elevated in OC, highlighting its potential clinical value in the diagnosis and prognosis of OC. Patients with lower METTL2B expression exhibited favorable survival. Furthermore, METTL2B knockdown significantly disrupted oncogenic behaviors in OC cell lines by suppressing the mTOR/AKT signaling pathway. Additionally, bioinformatics-based Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested a close correlation between METTL2B and immune responses. Conclusions Our research confirmed the upregulation of METTL2B in OC, suggesting its oncogenic function. However, METTL2B expression was negatively correlated with the infiltration scores of multiple immune cells, including cytotoxic cells and T cells, indicating its complex role in the tumor immune microenvironment. These findings highlight the significant clinical value of METTL2B in the diagnosis and prognosis of OC.

Keywords

• Ovarian cancer
• N3-methylcytidine
• METTL2B
• Immune infiltration