Wang Ling, Huang Chuanzhong, Lin Wansong, Zhou Zhifeng, Li Jieyu, Chen Mingshui, Zhang Lingyu, Ye Yunbin
Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014,China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014,China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
Ann Hepatol. 2025 Jan-Jun;30(1):101564. doi: 10.1016/j.aohep.2024.101564. Epub 2024 Sep 12.
To study the effect of eukaryotic initiation factor 3B (EIF3B) on the invasion and migration of hepatocellular carcinoma (HCC) and its potential mechanism.
The clinical significance of EIF3B expression was studied with The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interaction Analysis datasets. Immunohistochemical staining and western blotting were used to examine EIF3B expression in cell lines and tissues from HCC patients. The scratch assay and transwell assay were used to measure the invasion and metastasis of different HCC cell lines in vitro. The molecular mechanism of EIF3B was determined using RNA-seq and identification of dysregulated signaling pathways. Western blotting was used to verify the alterations of EIF3B signaling functioned in the promotion of HCC progression.
Elevated expression of EIF3B in HCC correlated significantly with aggressive clinicopathologic characteristics, including advanced tumor grade and poor prognosis. Studies with cultured cells indicated that EIF3B knockdown inhibited HCC cell invasion and metastasis by depressing the epithelial-mesenchymal transition (EMT). EIF3B also activated the TGFBI/MAPK/ERK signaling pathway by increasing the levels of pMEK and pERK.
Our results indicate that EIF3B functions as an oncogene in HCC that accelerates cell invasion, metastasis, and the EMT by stimulation of the TGFBI/MAPK/ERK signaling pathway. EIF3B is a potential target for the treatment of HCC.
研究真核生物起始因子3B（EIF3B）对肝细胞癌（HCC）侵袭和迁移的影响及其潜在机制。
利用癌症基因组图谱（TCGA）和基因表达谱交互分析数据集研究EIF3B表达的临床意义。采用免疫组织化学染色和蛋白质印迹法检测肝癌患者细胞系和组织中EIF3B的表达。划痕实验和Transwell实验用于体外检测不同肝癌细胞系的侵袭和转移能力。利用RNA测序和失调信号通路鉴定确定EIF3B的分子机制。蛋白质印迹法用于验证EIF3B信号改变在促进肝癌进展中的作用。
肝癌中EIF3B表达升高与侵袭性临床病理特征显著相关，包括肿瘤分级高和预后差。对培养细胞的研究表明，EIF3B基因敲低通过抑制上皮-间质转化（EMT）来抑制肝癌细胞的侵袭和转移。EIF3B还通过增加pMEK和pERK水平激活TGFBI/MAPK/ERK信号通路。
我们的结果表明，EIF3B在肝癌中作为一种癌基因发挥作用，通过刺激TGFBI/MAPK/ERK信号通路加速细胞侵袭、转移和EMT。EIF3B是肝癌治疗的潜在靶点。
