神经鞘瘤中miR-10b基因表达和甲基化水平分析  

Expression of miR-10b gene and methylation level in schwannomas

作　　者：郭建新[1] 高珂[2] 祁磊[2] 谢万福[2] 徐高峰[2] 冯怡[3] 李瑞春[2] GUO Jian-xin;GAO Ke;QI Lei;XIE Wan-fu;XU Gao-feng;FENG Yi;LI Ruichun(Department of Medical Image,the First Affiliated Hospitalof Xian Jiaotong University,Xi'an 710061;Department of Neurosurgery,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061;Department of Biomedical ngineering,Xi'an Jiaotong University,Xi'an 710049,China)

机构地区：[1]西安交通大学第一附属医院影像科,陕西西安710061 [2]西安交通大学第一附属医院神经外科,陕西西安710061 [3]西安交通大学生物医学工程系,陕西西安710049

出　　处：《西安交通大学学报（医学版）》2018年第1期97-101,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：西安交通大学综合交叉项目(No.xjj2014145)~~

摘　　要：目的分析miR-10b小RNA在神经鞘瘤中的表达水平和该基因上游甲基化水平,并识别miR-10b在神经鞘瘤中的潜在靶基因。方法应用实时定量PCR定量miR-10b及潜在靶基因HOXB3、HOXD10、PTEN、PIK3CA、MAPRE1、HADC4在13例神经鞘瘤和6例正常前庭蜗神经的表达;进一步分析差异表达基因与神经鞘瘤临床特征的相关性;最后应用焦磷酸测序分析两组之间miR-10b基因上游甲基化水平差异。结果与正常神经相比,神经鞘瘤组织中miR-10b分子表达水平显著升高(P=0.000 3),而PTEN表达显著下降(P=0.004 7),两者显著负相关(P=0.001,r=-0.689)。此外,miR-10b基因启动子区内甲基化水平下调,并与该基因表达显著负相关(P=0.011,r=-0.571)。miR-10b高表达组与低表达组比较,肿瘤直径有差异(P=0.016);但发病年龄及1年后肿瘤复发率无差异(P>0.05)。结论神经鞘瘤中miR-10b启动子甲基化水平下降引起该基因持续高表达,而miR-10b可能靶向抑制PTEN表达。Objective To analyze miR-10b expression level and the gene upstream methylation level in schwannomas so as to explore and identify the potential target genes for miR-10b in schwannomas.Methods The miR-10b with its potential target genes including HOXB3,HOXD10,PTEN,PIK3CA,MAPRE1and HADC4were quantitatively analyzed by PCR in13cases of schwannomas and6cases of human vestibulocochlear nerves.We studied the correlation between the differentially expressed genes and the clinical characteristics of schwannomas.Finally,the differences in miR-10b gene upstream methylation levels were measured and analyzed by pyrosequencing between schwannomas and normal vestibulocochlear nerves.Results Compared with that of normal nerves,the expression level of miR-10b was significantly higher(P=0.0003)while the level of PTEN was lower(P=0.0047)in schwannomas.Negative correlation existed between the levels of miR10b and PTEN(P=0.001,r=-0.689).Moreover,the methylation level of the miR-10b gene promoter was downregulated in schwannomas;it had negative correlation with the expression level of miR-10b(P=0.011,r=-0.571).There was a significant difference in tumor mass diameter between miR-10b higher expression group and lower group(P=0.016);however,there was no difference in age or recurrence rate(P>0.05).Conclusion The downregulation of methylation level of the promoter leads to higher expression of miR-10b gene,and it may targetedly inhibit the expression of PTEN.

关 键 词：神经鞘瘤 MIR-10B 甲基化 靶基因 

分 类 号：R73[医药卫生—肿瘤]