MicroRNA-490-5p靶向CDK1通过ERK信号通路参与胃癌细胞周期调控  

Overexpression of microRNA-490-5p targeting CDK1 suppresses proliferation and cell cycle progression of gastric cancer cells by inhibiting ERK signaling pathway

作　　者：侯东泽[1] 代劲松[1] 邓志波[1] 颜登高 

机构地区：[1]湖北省监利县人民医院普通外科,湖北监利433300

出　　处：《现代肿瘤医学》2017年第16期2565-2572,共8页Journal of Modern Oncology

摘　　要：目的:探讨miR-490-5p对胃癌细胞增殖与周期的调控作用和分子机制,以期为临床治疗胃癌提供新的有效靶点。方法:收集30例胃癌患者的胃癌组织及相应的癌旁组织标本;采用Real-time PCR法检测miR-490-5p和CDK1的表达水平;分析细胞周期相关蛋白CDK1与miR-490-5p的靶向关系。MTT法和流式细胞仪检测转染后胃癌细胞生长以及细胞周期情况。结果:与癌旁组织相比,胃癌组织中miR-490-5p的表达显著下调(P<0.001);转染miR-490-5p mimics的细胞中miR-490-5p的表达显著上调,而miR-490-5p inhibitors中miR-490-5p显著下降(均P<0.001);CDK1是miR-490-5p的靶基因;下调miR-490-5p、上调CDK1能促进胃癌细胞的增殖能力及G1/S期的转化(均P<0.001)。结论:通过上调miR-490-5p可以抑制胃癌细胞的恶性增殖,减少CDK1表达,抑制ERK信号途径,降低了G1/S期的转化速率,从而为胃癌诊断及治疗提供新靶标。Objective：To investigate the effects of microRNA-490-5p（miR-490-5p）on the cell proliferation and cell cycle progression in gastric cancer（GC）.Methods：Thirty GC tissues and relative adjacent normal tissues were collected.Quantitative real-time polymerase chain reaction（qRT-PCR）was performed to detect the expression of miR-490-5p and cyclin dependent kinases（CDK）.The target relationship of miR-490-5p and CDK1 was analyzed.Cell growth and cell cycle were detected using MTT assay and flow cytometry,respectively.Results：miR-490-5p was significantly down-regulated in GC tissues compared to that in the adjacent normal tissues（P〈0.001）.miR-490-5p was highly expressed in the cells transfected with miR-490-5p mimics but significantly down-regulated in those transfected with the miR-490-5p inhibitors（both P〈0.001）.miR-490-5p targeted CDK1.Down-regulating miR-490-5p and up-regulating CDK1 expression promoted the proliferation and G1/S transition of GC cells by targeting CDK1（all P〈0.001）.Conclusion：The proliferation of GC cells could be inhibited by up-regulating miR-490-5p.Over-expressed miR-490-5p could decrease the expression of CDK1 and inhibit ERK signaling pathway,which suppress the GC cell proliferation and G1/S transition.

关 键 词：胃癌 miRNA miR-490-5p CDK1 ERK 细胞周期 信号通路 细胞增殖 

分 类 号：R735.2[医药卫生—肿瘤]