Abstract
BACKGROUND: EIF3M, a core subunit of eukaryotic translation initiation factor 3, plays a pivotal role in protein synthesis by regulating the assembly of the 43S initiation complex. However, its biological functions in cancer remain poorly understood. To further investigate the clinical translational value and underlying mechanisms of EIF3M in tumors, this study conducted comprehensive bioinformatic analysis of EIF3M across various tumor types. METHODS: We utilized publicly available databases to perform a comprehensive bioinformatics analysis of EIF3M's biological roles in oncogenesis, aiming to elucidate its pan-cancer expression patterns and prognostic significance. Furthermore, we conducted an integrative multi-omics analysis incorporating methylation profiling, co-expressed gene networks, targeted miRNA interactions, and tumor immune microenvironment infiltration to decipher the complex regulatory architecture and biological pathways mediated by EIF3M across cancer types. Finally, we used HCC cell lines for in vitro functional validation, determining how EIF3M expression modulates malignant phenotypic behaviors in hepatocellular carcinoma. RESULTS: EIF3M was overexpressed in multiple cancers and correlated with advanced tumor stage and poor survival. Its dysregulation was primarily driven by gene amplification and regulated by promoter methylation and miRNAs. EIF3M functioned as a hub in cell cycle and transcriptional networks and was linked to an immunosuppressive microenvironment. In hepatocellular carcinoma models, EIF3M modulated tumor proliferation, migration, and activated oncogenic pathways like Wnt/β-catenin. CONCLUSION: This study reveals that EIF3M expression correlates with immune infiltration and poor prognosis in multiple cancers. In vitro experiments in hepatocellular carcinoma models demonstrated that EIF3M critically regulates malignant cell behaviors. Collectively, our findings highlight EIF3M's value as a promising pan-cancer biomarker worthy of further investigation for its utility in prognosis prediction and as an indicator of immunotherapeutic response.