真核生物翻译起始因子3亚基B通过CEBPB翻译促进头颈癌。

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

作者信息

Xu Chengzhi, Shen Yupeng, Shi Yong, Zhang Ming, Zhou Liang

机构信息

Department of Otolaryngology-Head and Neck Surgery, Eye Ear Nose and Throat Hospital, Fudan University, No. 83 Fenyang Road, Shanghai, 200031, China.

Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, China.

出版信息

Cancer Cell Int. 2022 Apr 22;22(1):161. doi: 10.1186/s12935-022-02578-y.

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.

背景

头颈部鳞状细胞癌（HNSCC）是全球第六大常见癌症类型。mRNA翻译失调是癌症的常见特征。真核翻译起始因子3亚基B（EIF3B）已被报道为一种癌基因；然而，其在HNSCC中的作用尚未完全阐明。

方法

在本研究中，基于TCGA数据集分析了EIF3B表达的临床意义。然后，敲低EIF3B表达并揭示其在HNSCC中的作用。为了探索EIF3B的分子机制，我们应用了RNA测序和蛋白质组学，并获得了失调的信号通路。进行RNA免疫沉淀（RIP）测序以揭示EIF3B的靶mRNA，并使用TCGA数据集验证EIF3B的潜在靶标。

结果

在HNSCC癌组织样本中观察到EIF3B表达升高。EIF3B的表达与患者的性别、年龄、HPV感染状态、T分期、N分期、神经周围侵犯状态和生存状态显著相关。EIF3B是HNSCC预后不良的一个标志物。EIF3B沉默的Fadu和Cal27细胞数量减少，EIF3B敲低诱导这两种细胞系发生凋亡。EIF3B沉默的细胞侵袭和迁移能力降低，EIF3B敲低组小鼠的肿瘤体积显著减小。结果表明，EIF3B促进CEBPB的翻译并激活MAPK信号通路，并且揭示了IL6R和CCNG2是EIF3B调节的CEBPB翻译的靶标。