EIF3B is associated with poor outcomes in gastric cancer patients and promotes cancer progression via the PI3K/AKT/mTOR signaling pathway
EIF3B is associated with poor outcomes in gastric cancer patients and promotes cancer progression via the PI3K/AKT/mTOR signaling pathway
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EIF3B 与胃癌患者的不良预后相关，并通过 PI3K/AKT/mTOR 信号通路促进癌症进展
DOI：
10.2147/cmar.s207834
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Ji, Jiafu
中科院分区：
文献类型：
--
作者：
Wang, Lin;Wen, Xianzi;Ji, Jiafu
目的：真核翻译起始因子（EIF）在蛋白质合成中起着至关重要的作用。 EIF3B是EIF3家族的核心亚基，在许多肿瘤中过度表达。 EIF3B与不良预后以及肿瘤的发生和发展有关。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进展中的临床意义和可能机制。方法：通过定量PCR分析78份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份GC组织样本中EIF3B的表达。在GC组织中分析EIF3B与临床病理特征之间的相关性。通过体外和体内测定研究了 EIF3B 在 GC 进展中的作用。结果：EIF3B 表达在 GC 组织中上调（73.4%，IHC）。 EIF3B的高表达与肿瘤浸润深度、淋巴结转移和TNM分期显着相关（P分别为0.000、0.000和0.000）。多变量分析表明，EIF3B 高表达的 GC 患者 5 年生存率较差。 EIF3B促进GC细胞增殖，并与GC样本中增殖细胞核抗原（PCNA）表达密切相关（P=0.009）。它还通过上皮间质转化 (EMT) 和 Stat3 信号通路增强肿瘤细胞的迁移和侵袭。 GC细胞中EIF3B的敲低抑制了异种移植肿瘤的生长和体内肺转移定植。此外，基因集富集分析（GSEA）和Western blot结果表明EIF3B激活PI3K/AKT/mTOR信号通路。结论：我们的结果表明EIF3B在GC进展中发挥致癌作用，并作为GC患者的独立预后因素。
Purpose: 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.Methods: 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.Results: 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 (P=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 (P=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.Conclusion: Our results suggest that EIF3B plays an oncogenic role in GC progression and serves as an independent prognostic factor for GC patients.