MiR-26a诱导人肝癌细胞凋亡的机制  

Mechanism of miR-26a Induced Apoptosis in Human Hepatocellular Carcinoma Cells

作　　者：邵青[1] 刘月[1] 宁守斌[1] 李白容[1] 步晓华[1] 朱鸣[1] 金晓维[1] 毛高平[1] 张亚飞[1] 

机构地区：[1]解放军空军总医院消化内科/全军小肠疾病内镜诊疗中心,北京100142

出　　处：《华南国防医学杂志》2015年第10期725-729,共5页Military Medical Journal of South China

基　　金：国家自然科学基金项目(81101533;81470818;81071727);中国人民解放军空军总医院院内课题(2014020)

摘　　要：目的探讨miR-26a转染诱导人肝癌细胞凋亡的可能机制。方法以miR-26a转染选择不同p53及Rb1基因背景人肝癌细胞系,检测其凋亡水平变化,并应用Western blot、双荧光素酶报告基因实验、免疫共沉淀等方法探讨其机制。结果在p53野生型HepG2细胞中,miR-26a转染可通过抑制其靶基因Rb1的表达,进而使得原与其结合的E2F1蛋白游离,由此诱导p53蛋白积聚活化,凋亡发生;而在p53突变型PLC/PRF/5细胞中,Rb1也是miR-26a的功能靶基因,但miR-26a转染并不能显著诱导细胞凋亡,虽其也导致突变型p53表达水平上调;而在不表达p53和Rb1基因的Hep3B细胞中,miR-26a转染未能显著诱导细胞凋亡。结论在人肝癌HepG2细胞中,Rb1是miR-26a的直接功能靶基因,miR-26a转染可通过p53依赖的Rb1/E2F1信号途径诱导细胞凋亡。Objective To investigate the possible mechanism of miR-26 a induced apoptosis in human hepatocellular carcinoma cells.Methods Apoptosis was detected in human hepatocellular carcinoma cells with various p53 or Rb1 gene background after miR-26 a transfection.Western blot analysis,luciferase assay and co-immunoprecipitation,etc.were performed to investigate the possible mechanism.Results In p53 wild-type HepG2 cells,miR-26 a transfection enhanced the level of free E2F1 protein by direct inhibiting the expression of Rb1,which resulted in the accumulation and activation of wild-type p53 protein and subsequent apoptosis.In p53 mutant PLC/PRF/5 cells,Rb1 was the direct functional target of miR-26 a,but miR-26 a transfection couldn＇t induce significant apoptosis even though the level of mutant p53 protein was observed to be increased.In Hep3 B cells without p53 and Rb1 gene expression,miR-26 a transfection couldn＇t induce significant apoptosis.Conclusion In HepG2 cells,Rb1 is the direct functional target of miR-26 a.MiR-26 a transfection can induce apoptosis through a p53-dependent manner involving Rb1/E2F1 pathway.

关 键 词：MiR-26a 肝癌细胞 凋亡 RB1 E2F1 

分 类 号：R735.7[医药卫生—肿瘤]