Gab1通过调控MAPK信号通路促进脑膜瘤细胞增殖和侵袭的机制研究  

Mechanism of Gab1 Promoting Proliferation, Invasion and Metastasis of Meningioma Cells by Regulating MAPK Signaling Pathway

作　　者：陈卫峰 吴倩岚[2] 张海青 邱贵峰 马文群[1] 张泰民[1] CHEN Wei-feng;WU Qian-lan;ZHANG Hai-qing;QIU Gui-feng;MA Wen-qun;ZHANG Tai-min(Department of Neurology,Handan Central Hospital,Handan 056000,China;Department of Pathology,Handan First Hospital,Handan 056000,China;Three Branches of Department of Surgery,Weixian Hospital of Traditional Chinese Medicine,Handan 056000,China)

机构地区：[1]邯郸市中心医院神经外一科,邯郸056000 [2]邯郸市第一医院病理科,邯郸056000 [3]魏县中医医院外三科,邯郸056000

出　　处：《中国临床神经科学》2021年第1期1-8,共8页Chinese Journal of Clinical Neurosciences

摘　　要：目的探究脑膜瘤组织中Grb2相关结合蛋白1(Gab1)的表达意义及经MAPK信号通路促进脑膜瘤细胞增殖和迁移的机制。方法临床收集62例脑膜瘤患者的瘤组织和瘤旁组织,通过免疫组化染色检测Gab1。分别将人脑膜瘤细胞系SF3061分为对照组、Gab1组和sh-Gab1组。通过质粒转染过表达或沉默Gab1,分别检测转染后各组细胞活力、增殖、迁移和侵袭功能,以及丝裂原活化蛋白激酶(MAPK)通路相关蛋白ERK1/2、JNK、P38 MAPK蛋白水平。结果脑膜瘤组织中的Gab1表达水平高于瘤旁正常组织(P<0.05)。脑膜瘤分级越高,组织中Gab1表达水平越高(P<0.05)。Gab1组蛋白和Gab1 mRNA水平显著下调(P<0.05),sh-Gab1组Gab1 mRNA和ERK1/2、JNK、P38MAPK蛋白水平显著上调(P<0.05)。CCK-8检测转染细胞活力、克隆形成数目、迁移和侵袭能力:Gab1组高于对照组(P<0.05),sh-Gab1组低于对照组(P<0.05)。ERK1/2、JNK、P38 MAPK蛋白:Gab1组高于对照组(P<0.05),sh-Gab1组低于对照组(P<0.05)。结论 Gab1在脑膜瘤中过表达,高Gab1水平与更高的脑膜瘤分级有关;Gab1通过调控MAPK通路上调ERK1/2、JNK、P38 MAPK蛋白促进脑膜瘤细胞的增殖、迁移和侵袭。Aim To explore the significance of Grb2-associated binding protein 1(Gab1) expression in meningiomas and the mechanism of promoting proliferation and migration through mitogen-activated protein kinase(MAPK) signaling pathway. Methods Clinically collected 62 cases of meningiomas and adjacent tissues. Gab1 was detected by immunohistochemical staining. Human meningioma cell line SF3061 was divided into a control group, a Gab1 group and a sh-Gab1 group. Gab1 was overexpressed or silenced by plasmid transfection. Cell viability, proliferation, migration, invasion function, and MAPK pathway levels in each group were measured after transfection. Results The expression level of Gab1 in meningiomas was higher than that in normal tissues adjacent to the tumor(P<0.05). Gab1 expression level was higher in meningiomas with higher decomposition(P<0.05). Gab1 mRNA and protein levels of meningiomas in Gab1 group were significantly reduced(P<0.05). Gab1 mRNA and protein levels were significantly up-regulated in sh-Gab1 group(P<0.05). CCK-8 was used to detect cell viability, colony formation number, migration and invasion ability of Gab1 group were significantly higher than those of the control group(P<0.05). CCK-8 was used to detect cell viability, number of clone formation, migration and invasion ability of sh-Gab1 group were significantly lower than those of the control group(P<0.05). ERK1/2、JNK、p38 MAPK proteins in Gab1 group were significantly higher than those in the control group(P<0.05). ERK1/2, JNK, p38 MAPK proteins in sh-Gab1 group were significantly lower than those in the control group(P<0.05). Conclusion Gab1 is overexpressed in meningioma, and high levels of Gab1 are associated with higher grade of meningioma. And Gab1 can promote the proliferation, migration and invasion of meningiomas cells by regulating the MAPK pathway.

关 键 词：脑膜瘤 Grb2相关结合蛋白1 增殖 侵袭 丝裂原活化蛋白激酶 MAPK通路 

分 类 号：R739.45[医药卫生—肿瘤]