microRNA-433在胃癌组织中的表达下降及对胃癌细胞系生长的影响  

Down-regulation of microRNA-433 expression in gastric cancer:Possible mechanisms involved

作　　者：李睿东[1] 韩高雄[1] 李伟[1] 陶凯雄[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院,湖北省武汉市430022

出　　处：《世界华人消化杂志》2012年第19期1726-1731,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81172294~~

摘　　要：目的:探讨胃癌组织中microRNA-433表达差异以及其可能下调的机制,及在低表达microRNA-433胃癌细胞系中提升其表达的量对细胞生长的影响.方法:取胃癌组织及其正常癌旁组织43例,实时定量检测两者表达差异,并结合病例分析.使用1、5、10mol/L5-Aza-CdR干预胃癌SGC-7901细胞,检测每组microRNA-433的表达变化.转染microRNA-433mimics进入SGC-7901细胞,用流式细胞术检测细胞增殖凋亡情况.结果:胃癌组织相对其正常癌旁组织,microRNA-433表达量明显减低,差异有明显统计学意义(P<0.05),microRNA-433表达与性别、分化、年龄无明显关系(P>0.05),同肿瘤分期有统计学意义(P<0.05).胃癌细胞系SGC-7901中microRNA-433的表达相对于正常胃黏膜上皮细胞GES-1明显减低.SGC-7901细胞通过甲基化酶抑制剂5-Aza-CdR以浓度1、5、10mol/L处理5d之后,分别检测microRNA-433的表达,相对未处理组,其表达均有上升并且呈现出剂量依赖性.将microRNA-433mimics转染至SGC-7901中提高其表达,通过流式细胞术检测发现,相比未处理组,提高表达后肿瘤细胞凋亡率上升,具有统计学意义(P<0.05).结论:microRNA-433在胃癌组织中表达减低,并且同肿瘤分期有关.使用5-Aza-CdR作用SGC-7901肿瘤细胞系后,microRNA-433的表达明显上升.其表达下调的机制可能是由于前端启动子区域高甲基化造成,转染提升肿瘤细胞中microRNA-433的表达,可以促进肿瘤细胞的凋亡.microRNA-433具有潜在的抑癌作用.AIM： To investigate the expression of microR- NA-433 in gastric cancer and to explore the pos- sible mechanisms involved. METHODS： The expression level of microR- NA433 in 43 cases of gastric cancer and matched adjacent normal tissue samples was examined by qRT-PCR. The relationship between mi- croRNA-433 expression and clinical features of gastric cancer was analyzed. Human gastric cancer SGC-7901 cells were treated with 1, 5, or 10 μmol/L of 5-Aza-CdR for five days, and the expression level of microRNA-433 in treated cells was determined. SGC-7901 cells were then transfected with a microRNA-433 mimic, and the proliferation and apoptosis of the transfected cells were examined by FCM. RESULTS： The expression level of microR- NA-433 was lower in gastric cancer than in normal gastric tissue （P 〈 0.05）. MicroRNA-433 expression was associated with tumor stage （P 〈 0,05）, but not with sex, age or tumor differentia- tion. The expression level of microRNA-433 in SGC-7901 cells was significantly lower than that in gastric mucosal cell line GES-1. Treatment of SGC-7901 cells with 5-Aza-CdR up-regulated microRNA-433 expression in a dose-dependent manner. Transfection of SGC-7901 cells with a mi- croRNA-433 mimic up-regulated the expression of microRNA-433 and increased cell apoptosis. CONCLUSION： The expression level of mi- croRNA-433 is lower in gastric cancer than in normal gastric tissue. MicroRNA-433 expres- sion correlates with tumor stage. Treatment of SGC-7901 cells with 5-Aza-CdR up-regulates mi- croRNA-433 expression possibly by regulating promoter methylation. Transfection of SGC-7901 cells with a microRNA-433 mimic accelerates apoptosis of tumor cells, suggesting that mi- croRNA-433 is a potent tumor suppressor.

关 键 词：microRNA-433 胃癌 甲基化 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]