Wang Lin, Wen Xianzi, Luan Fengming, Fu Tao, Gao Chao, Du Hong, Guo Ting, Han Jing, Huangfu Longtao, Cheng Xiaojing, Ji Jiafu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
Cancer Manag Res. 2019 Aug 21;11:7877-7891. doi: 10.2147/CMAR.S207834. eCollection 2019.
Eukaryotic translation initiation factor (EIF) plays a vital role in protein synthesis. EIF3B is a core subunit of the EIF3 family, and is overexpressed in many tumors. EIF3B is associated with an unfavorable prognosis, as well as the genesis and development of tumors. However, the potential role of EIF3B in gastric cancer (GC) remains unknown. In the current study, we explored the clinical significance and the possible mechanism of EIF3B in the progression of GC.
EIF3B expression was analyzed in 78 GC tissue samples through quantitative PCR and in 94 GC tissue samples through immunohistochemistry (IHC) staining. The correlation between EIF3B and clinicopathological features was analyzed in GC tissues. The role of EIF3B in GC progression was investigated through in vitro and in vivo assays.
EIF3B expression was upregulated in GC tissues (73.4%, IHC). High expression of EIF3B was significantly correlated with the depth of tumor invasion, lymph node metastasis and TNM stage (=0.000, 0.000 and 0.000, respectively). Multivariate analysis indicated that GC patients with high EIF3B expression suffered a poorer 5-year survival. EIF3B promoted GC cell proliferation and was strongly associated with proliferating cell nuclear antigen (PCNA) expression in GC samples (=0.009). It also enhanced tumor cell migration and invasion, which were affected through epithelial-mesenchymal transition (EMT) and the Stat3 signaling pathway. Knockdown of EIF3B in GC cells suppressed the growth of xenograft tumors and lung metastatic colonization in vivo. Furthermore, gene set enrichment analysis (GSEA) and Western blot results demonstrated that EIF3B activated the PI3K/AKT/mTOR signaling pathway.
Our results suggest that EIF3B plays an oncogenic role in GC progression and serves as an independent prognostic factor for GC patients.
真核生物翻译起始因子（EIF）在蛋白质合成中起关键作用。EIF3B是EIF3家族的核心亚基，在许多肿瘤中过表达。EIF3B与不良预后以及肿瘤的发生发展相关。然而，EIF3B在胃癌（GC）中的潜在作用仍不清楚。在本研究中，我们探讨了EIF3B在GC进展中的临床意义及可能机制。
通过定量PCR分析78例GC组织样本中的EIF3B表达，并通过免疫组织化学（IHC）染色分析94例GC组织样本中的EIF3B表达。分析GC组织中EIF3B与临床病理特征之间的相关性。通过体外和体内实验研究EIF3B在GC进展中的作用。
GC组织中EIF3B表达上调（IHC检测为73.4%）。EIF3B高表达与肿瘤浸润深度、淋巴结转移和TNM分期显著相关（分别为P = 0.000、0.000和0.000）。多因素分析表明，EIF3B高表达的GC患者5年生存率较差。EIF3B促进GC细胞增殖，且与GC样本中增殖细胞核抗原（PCNA）表达密切相关（P = 0.009）。它还增强肿瘤细胞迁移和侵袭，这是通过上皮-间质转化（EMT）和Stat3信号通路实现的。敲低GC细胞中的EIF3B可抑制体内异种移植肿瘤的生长和肺转移定植。此外，基因集富集分析（GSEA）和蛋白质印迹结果表明，EIF3B激活PI3K/AKT/mTOR信号通路。
我们的结果表明，EIF3B在GC进展中起致癌作用，并可作为GC患者的独立预后因素。
