巢蛋白基因沉默通过激活细胞周期依赖性激酶(cdk5)促进大鼠神经胶质瘤细胞C6的迁移和增殖(英文)  

Silencing of Nestin Promotes Glioma Cell Migration and Proliferation through Activation of Cyclin-dependent Kinase 5

作　　者：兰宝金[1] 鲁文静[2,3] 兰峰[2] 曹翠丽[4] 葛瑞民[2] 陈玲珑[1] 张小燕[2] 陆爱丽[2] 吴碧莲[1] 马晓雯[2] 沈丽[2] 

机构地区：[1]福建卫生职业技术学院,福州350001 [2]北京大学医学部细胞生物学系,北京100191 [3]香港大学医学院外科系,香港999077 [4]河北医科大学基础医学院神经生物学实验室,石家庄050000

出　　处：《中国生物化学与分子生物学报》2011年第5期419-425,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：Supported by Project of Education Department of Fujian Province(No.JA08257)~~

摘　　要：中间纤维蛋白巢蛋白(nestin)在各种胚胎前体细胞及成熟组织中均有表达.近年一些研究显示,巢蛋白的表达上调和一些恶性肿瘤的病理特征有相关性.但是,巢蛋白在干细胞分化及肿瘤发生中的作用还不为人知.在本研究中,我们运用短发卡状的RNA为工具,以大鼠神经胶质瘤细胞系C6为模型,对巢蛋白的功能进行了研究.划痕实验和迁移实验的结果均显示,巢蛋白基因沉默可以促进C6细胞的迁移.同时,BrdU渗入实验显示,此过程伴随着细胞增殖的增加.进一步研究显示,细胞周期依赖性激酶cdk5的活性在此过程中有显著的增加.此外,巢蛋白基因沉默所引起的迁移改变可以被cdk5特异性抑制剂roscovitine所回复,而对细胞增殖则没有显著影响.综上所述,本研究揭示了巢蛋白基因沉默与神经胶质瘤细胞的迁移和增殖相关,而cdk5是此过程的重要调节因子.Nestin is an intermediate filament protein expressed in the progenitor cells of various embryonic and adult tissues.Recently,studies have indicated that overexpression of nestin associated with clinical pathology of several malignant tumors.However,little is known about the function of nestin in both stem cell differentiation and cancer carcinogenesis.In the study,we used short hairpin RNA transfection to investigate the function of nestin in C6 glioma cells.The results indicated that nestin silencing increased cell motility from both wound healing and transwell assays and moderately elevated cell proliferation from the BrdU incorporation assay.The nestin knockdown induced increase of Cdk5kinase activity could be reversed by the Cdk5 specific inhibitor roscovitine.This study showed that Cdk5was an important regulator to mediated the function of nestin in cell mortality and proliferation in glioma cells.

关 键 词：中间纤维 巢蛋白 RNA干扰 迁移 增殖 

分 类 号：Q78[生物学—分子生物学]