Eukaryotic translation initiation factor 3 subunit B promotes head and neck cancer via CEBPB translation

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. Deregulation of mRNA translation is a frequent feature of cancer. Eukaryotic translation initiation factor 3 subunit B (EIF3B) has been reported as an oncogene; however, its role in HNSCC has yet to be fully elucidated. Methods: In this study, the clinical significance of EIF3B expression was analyzed based on TCGA datasets. Then, EIF3B expression was knocked down and its role in HNSCC was revealed. To explore the molecular mechanisms of EIF3B, we applied RNA sequencing and proteomics and acquired deregulated pathways. RNA immunoprecipitation (RIP) sequencing was conducted to reveal the target mRNAs of EIF3B, and TCGA datasets were used to validate potential targets of EIF3B. Results: Elevated expression of EIF3B was observed in the HNSCC cancer samples. The expression of EIF3B was significantly correlated with the patient’s sex, age, HPV infection status, T stage, N stage, perineural invasion status and survival status. EIF3B serves as a marker of an unfavorable HNSCC prognosis. EIF3B-silenced Fadu and Cal27 cells exhibited reduced cell numbers, and EIF3B knockdown induced apoptosis in both cell lines. The EIF3B-silenced cells demonstrated decreased invasion and migration capabilities, and the EIF3B knockdown group mice showed significantly decreased tumor volumes. The results show that EIF3B promotes CEBPB translation and activates the MAPK pathway and revealed that IL6R and CCNG2 are targets of EIF3B-regulated CEBPB translation. Conclusion: In summary, the results indicated that EIF3B is a novel oncogene in HNSCC that promotes CEBPB translation and IL6R expression, and these findings provide a link between the molecular basis and pathogenesis of HNSCC. Graphical Abstract: [Figure not available: see fulltext.]