MiR-219-5p对人脑成胶质细胞瘤恶性表型的影响  

Effect of miR-219-5p on malignant phenotype of glioblastoma cells

作　　者：刘彦伟[1] 颜伟[1] 王永志[1] 张伟[1] 游赣[1] 唐铠[1] 

机构地区：[1]首都医科大学附属北京天坛医院神经外科,北京100050

出　　处：《肿瘤》2012年第6期395-401,共7页Tumor

基　　金：国家重点基础研究发展计划("973")(编号:2007CB512503)

摘　　要：目的:探讨miR-219-5p对人脑成胶质细胞瘤(glioblastoma,GBM)的恶性表型——增殖、凋亡和侵袭的影响,初步寻找与miR-219-5p发挥抑癌作用有关的靶点基因。方法:在60例GBM组织中分析miR-219-5p表达水平及mRNA表达谱,筛选与miR-219-5p表达量呈负相关的mRNA;选取前50个相关性最大的mRNA,用基因功能分析软件DAVID从中筛选出与GBM恶性进展相关的2组mRNA;最后用4个在线靶点预测网站从这2组中预测miR-219-5p的潜在靶点。采用MTT法、流式细胞术和Transwell实验初步验证miR-219-5p对GBM细胞增殖、凋亡和侵袭的影响。结果:60例GBM组织中筛出14个与增殖和凋亡相关的基因和5个与侵袭相关的基因(P<0.001);在这19个候选基因中预测到4个基因(TWIST1、MYO1B、WEE1和SPRED2)是miR-219-5p的潜在靶点。实验初步证明,miR-219-5p能够抑制GBM细胞的增殖和侵袭以及促进细胞凋亡(P<0.05)。结论:MiR-219-5p可能通过作用于多个靶点对GBM的恶性表型起到抑制作用。ObJective： To investigate the effect of miR-219-5p on malignant phenotype of glioblastoma cells involving proliferation, apoptosis and invasion, and to preliminarily determine the candidate target genes of miR-219-5p related to the inhibition of cancer. Methods： The inverse relationship between mRNAs and miR-219-5p in glioblastoma tissues from sixty cases was obtained by analysis of miR-219- 5p expression level and mRNA expression profiling. DAVID software for functional analysis was employed to analyze the functions of the top 50 mRNAs and screen out two sets of mRNAs related to glioblastoma progression. The target genes of miR-219-5p were screened out from the two sets of miRNAs on four websites of online target-binding prediction. MTT assay, flow cytometry （FCM） assay and Transwell assay were performed to detect the effects of miR-219-5p on the proliferation, apoptosis and invasion of human glioblastoma cells, respectively. Results： Fourteen proliferation/apoptosis-related genes and five invasion-related genes were screened from glioblastoma tissues of sixty patients （P〈0.001）. Four genes including TWIST1, MYO1B, WEE1 and SPRED2 were predicted as potential target genes of miR-219-5p from 19 candidate genes. Functional analysis revealed that miR-219-5p could suppress the proliferation and invasion of glioblastoma cells as well as promote the apoptosis （P〈0.05）. Conclusion： MiR-219-5p may suppress the malignant phenotype of glioblastoma cells through multiple gene targets.

关 键 词：成胶质细胞瘤 微RNAS 癌基因 细胞增殖 细胞凋亡 细胞侵袭 miR-219-5p 

分 类 号：R739.41[医药卫生—肿瘤]