肝细胞癌中Kruppel样因子4与叉头框蛋白M1基因表达相关性及临床意义  

Study on correlation between KLF4 and FOXM1 and its clinical significance in hepatic cellular cancer

作　　者：田川[1] 叶庆旺 姚姗姗[1] 高勇[1] 杨宁[2] 李琦[1,3] 

机构地区：[1]同济大学附属东方医院肿瘤科,上海200120 [2]第二军医大学附属东方肝胆医院肝外科,上海200438 [3]上海交通大学附属第一人民医院肿瘤中心,上海200080

出　　处：《兰州大学学报（医学版）》2015年第5期1-6,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：国家自然科学基金项目(81272714;81572310);上海市浦东新区卫生系统重点学科群建设项目(PWZxq2014-04);上海市浦东新区卫生系统领先人才培养计划项目(PWRL2013-02)

摘　　要：目的探讨人肝细胞癌中核转录因子Kruppel样因子4(KLF4)与叉头框蛋白M1(FOXM1)基因表达相关性,以及两种转录因子表达对肝细胞癌生长和增殖的影响。方法采用实时荧光定量PCR技术检测50例肝细胞癌患者肝癌组织及8株肝癌细胞中KLF4m RNA和FOXM1 m RNA表达水平并分析其相关性;KLF4过表达质粒和KLF4 si RNA分别转染人肝癌细胞Hep3B和BEL-7402,采用实时荧光定量PCR、蛋白印迹实验检测KLF4 m RNA、FOXM1m RNA及KLF4蛋白、FOXM1蛋白表达水平;通过CCK8实验检测KLF4和FOXM1基因对细胞增殖的影响。结果肝癌组织和细胞中KLF4低表达,而FOXM1高表达,两者呈负相关(r=-0.462,P=0.001);KLF4基因过表达抑制肝癌细胞增殖,而FOXM1基因过表达促进肝癌细胞增殖,FOXM1基因过表达能恢复KLF4对肝癌细胞抑制增殖作用。结论在肝细胞癌中,KLF4和FOXM1基因表达呈负相关,两者不同的表达水平可影响肝癌细胞的增殖。Objective To investigate the correlation between nuclear transcription Kruppel- like factor 4（KLF4）and forkhead box protein M1（FOXM1）in human hepatocellular carcinoma and their effect on cell growth and proliferation. Methods KLF4 and FOXM1 mRNA expression were detected by Real- time PCR in 50 cases specimens of hepatocellular carcinoma patients and 8 liver cancer cell lines, and the correlation between KLF4 and FOXM1 were analyzed. After BEL-7402 and Hep3 B cell lines were transfected by KLF4overexpression plasmid and KLF4 siRNA, KLF4 and FOXM1 expression was checked by Real- time PCR and Western blot. The effect of KLF4 and FOXM1 gene on cell proliferation was tested by CCK8 assay. Results Expression of KLF4 was decreased in primary HCC specimens and liver cancer cell lines, while expression of FOXM1 was increased, FOXM1 was negatively correlated with KLF4（r =-0.462, P = 0.001）.KLF4 overexpression can inhibit the proliferation of liver cancer cells,FOXM1 overexpression can promote cells proliferation and restore the effect of KLF4 on proliferation of liver cancer cells. Conclusion The expressions of KLF4 and FOXM1 were negatively correlated in hepatocellular carcinoma, their expression levels can affect the proliferation of hepatocelluar carcinoma cells.

关 键 词：肝细胞癌 Kruppel样因子4 叉头框蛋白M1 增殖 

分 类 号：R735.7[医药卫生—肿瘤]