摘要
目的检测分析异染色质蛋白1结合蛋白3(heterochromatin protein 1 binding protein 3,HP1BP3)在肝细胞癌中的表达及其对细胞恶性生物学行为的影响。方法应用TCGA数据库分析肝细胞癌与癌旁组织中HP1BP3基因的表达差异。生存检验分析HP1BP3表达与肝细胞癌患者总生存期的关系,单因素及多因素分析相关危险因素。应用Western blot和免疫组化法检测HP1BP3蛋白表达水平。用小干扰RNA(siRNA)分别转染Huh7、HepG2细胞,功能实验检测细胞增殖、迁移和侵袭能力。通过GSEA分析对其作用机制进行探究。结果TCGA数据库分析结果显示,HP1BP3基因在肝细胞癌组织中的表达明显高于非肿瘤组织(P<0.01),高表达组患者的总生存期较低表达组短(P=0.029)。HP1BP3基因是肝细胞癌的独立预测因子(P=0.024)。体外实验结果显示,HP1BP3基因在肝癌细胞株及肝细胞癌组织中表达上调。沉默HP1BP3基因可抑制肝癌细胞的增殖、侵袭和迁移。HP1BP3高表达与泛素化(P<0.001)、核酸切除修复(P<0.001)、RNA降解(P<0.001)、ERBB信号通路(P<0.001)、细胞周期(P<0.001)、细胞凋亡(P<0.001)通路有关。结论HP1BP3基因在肝细胞癌组织中表达上调,是肝细胞癌独立的预后危险因素,可促进肝细胞癌的发生、发展。
Purpose To detect and analyze the expression of heterochromatin protein 1 binding protein 3(HP1BP3)in hepatocellular carcinoma(HCC)and its effect on cell malignant biological behavior.Methods The difference of HP1BP3 gene expression was analyzed between hepatocellular carcinoma and paracancerous tissues in tumor genome map(TCGA)database.The relationship between the expression level and the overall survival rate of HCC patients was analyzed by survival test,univariate and multivariate analysis of related risk factors.Western blot and immunohistochemistry were used to verify the level of protein expression.Small interference RNA(siRNA)was transfected into Huh7 and HepG2 cells respectively,and the proliferation,migration and invasion of the cells were detected by functional assay.The mechanism of its action was explored by GSEA gene enrichment analysis.Results TCGA database analysis showed that the expression of HP1BP3 gene in HCC tissues was significantly higher than that in non-tumor tissues(P<0.01),and the survival rate of patients with high expression was shorter than that of patients with low expression(P=0.029).HP1BP3 gene was an independent predictor of liver cancer(P=0.024).In vitro,the expression of HP1BP3 gene was up-regulated in hepatocellular carcinoma cell lines and liver cancer tissues.Down-regulation of HP1BP3 gene inhibited the proliferation,invasion and migration of hepatocellular carcinoma cells.The high expression of HP1BP3 was related to ubiquitin(P<0.001),nucleic acid excision and repair(P<0.001),RNA degradation(P<0.001),ERBB signal pathway(P<0.001),cell cycle(P<0.001)and apoptosis pathway(P<0.001).Conclusion HP1BP3 gene is significantly up-regulated in hepatocellular carcinoma,which is an independent prognostic risk factor for hepatocellular carcinoma and can promote the occurrence and development of hepatocellular carcinoma.
作者
黄家利
徐畅
吴虹
葛颂
王飞通
牛坚
HUANG Jia-li;XU Chang;WU Hong;GE Song;WANG Fei-tong;NIU Jian(Xuzhou Medical University,the First Clinical Medical College,Xuzhou 221002,China;Department of General Surgery,Jiangsu Jianhu People’s Hospital,Yancheng 224700,China;Department of General Surgery,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221002,China)
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2022年第6期653-658,共6页
Chinese Journal of Clinical and Experimental Pathology
基金
江苏省自然科学基金(BK20161176)。
