干扰Mig-6基因表达对非小细胞肺癌EGFR信号通路的影响

Effect of interfering Mig-6 gene expression on EGFR pathway in non small cell lung cancers

目的:探讨干扰丝裂原诱导因子-6(Mig-6)基因表达对非小细胞肺癌表皮生长因子受体(EGFR)信号通路的影响。方法:A549、H1650细胞系均分为阴性对照组(si-NC组)和阳性实验组(si-Mig-6组),si-Mig-6组采用特异性小干扰RNA(siRNA)干扰Mig-6表达,si-NC组仅加入不含质粒的空载体,转染后采用MTT法检测细胞增殖能力,检测各组细胞侵袭能力和EGFR、ERK、AKT的蛋白及mRNA表达水平。结果:siRNA转染72 h后,si-Mig-6组Mig-6 mRNA及蛋白表达均显著低于si-NC组(P<0.05),细胞增殖能力显著高于siNC组,细胞侵袭能力亦显著高于si-NC组(P<0.05)。Mig-6对EGFR信号通路具有负向调控作用,干扰Mig-6表达,si-Mig-6组EGFR、细胞外调节蛋白激酶(ERK)、丝氨酸苏氨酸蛋白激酶(AKT)蛋白及mRNA表达均显著高于si-NC组(P<0.05)。结论:干扰Mig-6表达能够增强非小细胞肺癌增殖、侵袭能力,其可能通过对EGFR通路的负向调控而实现这一生物学功能,Mig-6有望成为治疗非小细胞肺癌一个潜在基因靶点。

Objective： To explore the effect of interfering Mig-6 gene expression on EGFR pathway in non small cell lung cancers.Methods： A549, H1650 cell lines were divided into negative control group（si-NC group） and the positive experimental group（si-Mig-6 group）.The si-Mig-6 group was interfered by siRNA, while the Si-NC group was transfected with empty vector.After transfection, the cell proliferation and invasion ability and the expression of EGFR, ERK, AKT mRNA and protein were determined by MTT assay.Results： After 72 h of siRNA transfection, the expression of Mig-6 mRNA and protein in si-Mig-6 group was significantly lower than that in si-NC group（P＆lt;0.05）.The cell proliferation and invasion ability in si-Mig-6 group were significantly higher than those in si-NC group（P＆lt;0.05）.Mig-6 was negatively correlated with EGFR signaling pathway.When interfering Mig-6 expression,the expression of EGFR, ERK, AKT protein and mRNA in si-Mig-6 group were significantly higher than that in group si-NC group（P＆lt;0.05）.Conclusion： Interference of Mig-6 expression can enhance proliferation and invasion ability in non small cell lung cancers,which may be related to negative regulation of EGFR pathway.Mig-6 is expected to become a potential gene therapy target for non-small cell lung cancers.