MOB1蛋白通过调控AKT/Cyclin D1信号通路促进肝癌细胞增殖

目的探讨MOB1蛋白在肝癌中的作用及其调控机制。方法利用癌症基因组图谱(TCGA)数据库分析MOB1在肝癌中的表达水平及其与患者生存期的关系。利用Western blotting验证MOB1蛋白在肝癌组织样本中的表达情况。用siRNA敲低MOB1表达,慢病毒构建MOB1稳定过表达细胞系,CCK-8法检测MOB1蛋白对肝癌细胞增殖的影响,流式细胞术检测MOB1蛋白对肝癌细胞周期的影响。Western blotting检测关键信号通路蛋白水平的表达。结果通过TCGA数据库分析,同源基因MOB1a和MOB1b在肝癌样本集中存在显著高表达,且肿瘤样本高表达MOB1a和MOB1b基因与患者的生存期缩短显著相关。在临床样本分析中,MOB1在86.7%的肝细胞癌患者肿瘤组织中显著高表达。MOB1过表达后Huh7和HepG2细胞的增殖速度显著上升,G₂/M期细胞比例显著上升。反之,MOB1敲低后,Huh7和HepG2细胞的增殖速率显著下降,G₂/M期细胞比例显著下降。进一步研究发现,MOB1蛋白过表达不影响经典的Hippo-YAP信号通路,但能促进AKT蛋白...

MoB1 protein promotes cell proliferation of liver carcinoma through AKT/Cyclin d1 signaling pathway

Objective To investigate the role of MOB1 protein in liver carcinoma and to explore the underlying mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression level of MOB1 in liver carcinoma and its relationship with liver carcinoma patient survival. Western blotting was used to verify the expression of MOB1 protein in liver carcinoma samples. Small interfer RNA (siRNA) was used to knock-down MOB1 protein, and lentivirus was used to construct stable MOB1 overexpression cell lines. The effect of MOB1 protein on cell proliferation of liver carcinoma was detected by CCK-8 method, and the effect of MOB1 protein on cell cycle of liver carcinoma was detected by flow cytometry. Western blotting was used to detect the expression of key signaling pathway proteins. Results TCGA database analysis showed that the homologous genes MOB1a and MOB1b were significantly overexpressed in liver carcinoma samples and the high expressions of MOB1a and MOB1b genes were significantly correlated with the shortened survival of liver carcinoma patients. In clinical sample analysis, MOB1 was significantly overexpressed in 86.7% hepatocellular carcinoma patients. After MOB1 protein overexpression, the cell proliferation rate in Huh7 and HepG2 cell lines increased significantly, and the proportion of cells in G₂/M phase increased significantly. On the contrary, after MOB1 protein knocked-down, the cell proliferation rate in Huh7 and HepG2 cell lines decreased significantly, and the proportion of cells in G₂/M phase decreased significantly. Further studies showed that MOB1 overexpression did not affect the classical Hipo-YAP signaling pathway, but could promote the phosphorylation of AKT and increase the level of Cyclin D1. Conclusion MOB1 protein may promote the cell proliferation of liver carcinoma and affect its progression by regulating AKT/Cyclin D1 signaling pathway.