脑胶质瘤中IMP3的表达与PI3K/AKT信号通路相关性及靶向干预

Expression of IMP3 in brain glioma and its correlation with PI3K/AKT and its clinical relevance

目的探讨胰岛素样生长因子Ⅱ mRNA结合蛋白3(insulin-like growth factor-Ⅱ mRNA-binding protein 3,IMP3)、磷酸肌醇三磷酸激酶-丝氨酸(phosphatidylinsitol 3-OH kinase-RAC-alpha serine,PI3K)、苏氨酸蛋白激酶(threonine-protein kinase,AKT)蛋白在人脑胶质瘤组织及细胞中的表达及相关性。方法采用免疫组织化学方法检测53例人脑胶质瘤组织及20例非瘤脑组织中IMP3,PI3K及AKT蛋白的表达情况;采用Westen-Blot及RT-PCR方法检测瞬时干扰IMP3基因后的胶质瘤U138细胞株IMP3、PI3K的蛋白及基因表达情况;检测抑制剂LY294002抑制U138细胞株的PI3K/AKT信号通路后相关蛋白IMP3、PI3K的表达情况。结果人脑胶质瘤组织中IMP3(P均=0.000),PI3K(P均=0.000)和AKT(P均=0.000)蛋白的表达均高于非瘤脑组织中的表达,且表达程度(中重度阳性表达率,P均=0.000)随肿瘤病理级别升高而增高。胶质瘤U138细胞株干扰IMP3基因后,IMP3蛋白(P=0.038)及基因(P=0.031)的表达均降低,PIK3蛋白(P=0.019)及基因(P=0.023)的表达均降低,LY294002抑制U138细胞株的PI3K/AKT信号通路后,PI3K蛋白(P=0.039)及基因(P=0.035)的表达均降低,而IMP3的蛋白(P=0.907)及基因(P=0.102)表达没有明显变化。结论IMP3、PI3K、AKT蛋白的表达与胶质瘤的组织病理分级、肿瘤细胞增殖密切相关,IMP3与PI3K/AKT具有相关性,且有望成为治疗胶质瘤的一个新靶点。

Objective To investigate the expression and correlation of insulin-like growth factor-Ⅱ mRNA-binding protein 3（IMP3）,phosphatidylinsitol 3-OH kinase-RAC-alpha serine（PI3K）,threonine-protein kinase（AKT）in human glioma tissues and cells.Methods Expression of IMP3,PI3K,AKT protein was examined using S-P immunohistochemsitry in 53 cases of gliomas and 20 cases of normal brain tissues.Western-blot and Real-time fluorescence quantitative PCR detected the expression of IMP3 and PI3K in glioma U138 cell by transient interference with the IMP3,and the expression of IMP3 and PI3K in glioma U138 cell with the inhibitor LY294002.ResultsPositive expression levels of IMP3（P=0.000）,PI3K（P=0.000）and AKT（P=0.000）in glioma tissues were significantly higher than those in normal brain tissues.The expression levels of IMP3（P=0.000）,PI3K（P=0.000）and AKT（P=0.000）were positively correlated with the pathologic stage.The expression levels of IMP3 protein（P=0.038）and gene（P=0.031）decreased with interfering IMP3 gene in U138 glioma cell line,and the expression levels of PI3K protein（P=0.019）and gene（P=0.023）decreased with interfering IMP3 gene in U138glioma cell line.The expression of IMP3 protein（P=0.907）and gene（P=0.102）did not significantly change with inhibitor LY294002 in U138 cell line,but the expression of PI3K protein（P=0.039）and gene（P=0.035）decreased in these groups.Conclusion IMP3,PI3K and AKT contribute to the progression of gliomas and the detection of IMP3 and PI3K/AKT maybe helpful to evaluate the course of disease.IMP3 might be possible novel target for molecular treatment of gliomas.