微小RNA-223及其标靶基因c-myc在肝癌发病中的作用  

Role of microRNA-223 and its target gene oncogene c-myc in hepatocellular carcinoma pathogenesis

作　　者：赵文月[1] 王冬冬[1] 宋孟镝[1] 杨玲[1] 叶进[1] 陈立波[2] 

机构地区：[1]华中科技大学附属协和医院消化科,武汉430032 [2]华中科技大学附属协和医院肝胆外科,武汉430032

出　　处：《中华肝脏病杂志》2011年第2期114-117,共4页Chinese Journal of Hepatology

基　　金：国家自然科学基金（30672067）

摘　　要：目的探讨微小RNA－223（miR－223）对原癌基因c-myc的调控及其在肝癌发病中的作用。方法通过实时定量聚合酶链反应和Westernblot检测正常肝脏组织、癌旁组织、肝癌组织及肝癌HepG2细胞、胎肝L02细胞中miR-223和c-myc的mRNA和蛋白质表达水平。构建miR－223模拟物（mimics）上调肝癌细胞HepG2中miR－223表达后，实时定量聚合酶链反应和Westernblot检测HepG2细胞中c-myc表达水平的变化。分别用独立样本t检验和单因素方差分析进行两组及多组数据间的比较，P〈0．05为差异有统计学意义。结果miR-223在正常肝组织、癌旁组织和肝癌组织中的相对表达量分别为0．055±0．015、0．030±0．008和0．020±0．016，肝癌组织低于正常肝组织（t=-0．031，P〈0．05）。miR-223在HepG2细胞中的表达较L02细胞下调（0．005±0．003比0．011±0．006，t=12．74，P〈0．01）。c-mycmRNA在正常肝组织、癌旁组织和肝癌组织中的相对表达量分别为0．029±0．023、0．136±0．071和0．425±0．026，肝癌组织高于正常肝组织（t=-0．317，P〈0．05）；c-myc蛋白在正常肝组织、癌旁组织和肝癌组织中的相对表达量分别为0．137±0．015、0．299±0．033和0．439±0．027，差异有统计学意义（F=103．35，P〈0．01）。miR-223mimics转染HepG2细胞后，c-myc蛋白在空白组、转染组和阴性对照组的相对表达量分别为0．423±0．041、0．116±0．015和0．432±0．034，转染组较其他两组明显降低（F=94．93，P〈0．05）。结论miR-223在肝癌组织中表达下调，丧失其对c-myc表达的抑制而导致c-myc异常高表达可能是肝癌发生的重要机制。Objective To investigate the regulatory role of microRNA-223 （miR-223） on c-myc and its role in hepatocarcinogenesis. Method miR-223 and c-myc mRNA expressions in normal tissue, paraneoplastic tissue, liver cancer tissue and liver cancer cells were tested with microRNA microarray and quantitative real-time PCR （qRT-PCR）. C-myc protein expression was detected by Western blot. MiR-223 mimic was transfected into HepG2 cells and the expression changes of c-myc mRNA and protein were tested with qRT-PCR and Western blot respectively. Results MiR-223 was down-regulated by 61.53% and 30.77% respectively in hepatocellular carcinoma and adjacent tissues as compared to normal liver tissues and the expression of miR-223 was also decreased in HepG2 cell as compared to fetal liver cells L02, whereas the expressions of c-myc mRNA and protein increased in paraneoplastic and HCC tissues compared with normal liver tissues. It prompts that the expressions of miR-223 and c-myc are negatively correlated. No obvious difference found among c-myc mRNA expressions after miR-223 mimics transfection. Conclusions The c- myc abnormal high-expression may play a dynamic role in hepatocarcinogenesis due to the miR-223 down-regulation.

关 键 词：癌 肝细胞 基因 MYC 微/小RNA-223 

分 类 号：R735.7[医药卫生—肿瘤]