AP4在人脑胶质瘤组织中的表达及其对胶质瘤细胞增殖、迁移和侵袭的影响

Expression of AP4 in human glioma tissue and its effect on the proliferation,migration and invasion of glioma cells

目的:探讨激活增强子结合蛋白4(activating enhancer binding protein 4,AP4)在人脑胶质瘤组织中的表达及其对胶质瘤细胞增殖、迁移和侵袭的影响。方法:收集29例神经胶质瘤组织和癌旁组织,采用免疫组织化学技术、RT-qPCR技术、Western blotting检测AP4在胶质瘤组织和癌旁组织中的表达。采用小干扰RNA(siRNA)构建AP4敲除的U251和U87细胞系,采用CCK-8实验、细胞划痕实验、Transwell实验检测胶质瘤细胞增殖、迁移和侵袭能力的改变。结果:AP4蛋白在胶质瘤组织中阳性表达率为72.41%(21/29),明显高于癌旁组织中的31.03%(9/29)(P<0.01)。Ⅰ+Ⅱ级、Ⅲ+Ⅳ级胶质瘤组织中AP4 mRNA和蛋白表达水平均明显高于相应癌旁组织(P<0.01),且Ⅲ+Ⅳ级胶质瘤组织中AP4 mRNA和蛋白表达均高于Ⅰ+Ⅱ级(P<0.05)。AP4敲除后,U251和U87细胞增殖能力均明显下降(P<0.01),迁移和侵袭能力亦均明显降低(P<0.01)。结论:AP4在神经胶质瘤组织和细胞中高表达,且与胶质瘤细胞增殖、迁移和侵袭能力密切相关,可能成为神经胶质瘤不良预后的重要参考指标。

Objective:To investigate the expression of activating enhancer binding protein 4(AP4)in human glioma tissue and its effect on the proliferation,migration and invasion of glioma cells.Methods:Tumor and adjacent tissues from 29 patients with gliomas were collected.The expression of AP4 in glioma tissues and adjacent tissues were measured by immunohistochemistry,RT-qPCR and Western blotting.Further,the AP4 knockout U251 and U87 cell lines were constructed using small interfering RNA(siRNA).The effect of AP4 knockdown on the proliferation,migration and invasion of glioma cells were detected by CCK-8,wound healing and Transwell test.Results:The positive expression rate of AP4 protein in glioma was 72.41%(21/29),which was significantly higher than that in adjacent tissues[31.03%(9/29)](P<0.01).The expression levels of AP4 mRNA and protein in gradeⅠ+ⅡandⅢ+Ⅳgliomas were significantly higher than those in adjacent tissues(P<0.01),and the expression levels in gradeⅢ+Ⅳgliomas were higher than those in gradeⅠ+Ⅱ(P<0.05).After AP4 knockout,the proliferation,migration and invasion of U251 and U87 cells decreased significantly(P<0.01).Conclusions:The expression level of AP4 is aberrant upregulated in glioma tissues and cells,and is closely related to the proliferation,migration and invasion of glioma cells.It can be a potential reference index for the poor prognosis.