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目的:探讨微小RNA(miR)-432与异柠檬酸脱氢酶(n IDH)野生型胶质瘤的细胞增殖迁移、患者总生存期及三基序蛋白质38(n TRIM38)基因表达的关系。n 方法:(1)下载中国胶质瘤基因组图谱(CGGA)数据库中198例胶质瘤患者(81例n IDH突变型、106例n IDH野生型、11例未知型)的临床资料、miRNA表达芯片数据及5例非肿瘤对照脑组织样本的miRNA表达芯片数据,比较miR-432在不同n IDH突变状态的胶质瘤亚型间及与非肿瘤对照样本间的表达差异。依据n IDH野生型胶质瘤样本中miR-432表达水平的中位值,将患者分为miR-432高表达组(n n=51)与miR-432低表达组(n n=53),采用Kaplan-Meier生存分析比较2组间总生存期的差异。采用单因素Cox回归分析和多因素Cox回归分析筛选n IDH野生型胶质瘤患者总生存期的影响因素。应用Pearson相关性分析检验n IDH野生型胶质瘤样本中miR-432与n TRIM38基因表达水平的关系。(2)体外培养人胶质瘤细胞系U251,并分为miR-432无义序列对照组和miR-432类似物组。采用细胞计数试剂(CCK)-8法检测2组细胞培养第1~5天时的活性,采用Transwell小室实验检测2组细胞的迁移能力,采用实时荧光定量PCR(RT-qPCR)法检测2组细胞中n TRIM38 mRNA的表达水平。(3)分别将野生型及突变型含TRIM38 3'-末端非翻译区(3'-UTR)的pGL3荧光报告载体结合miR-432无义序列、miR-432类似物转染U251细胞,分为miR-432无义序列+野生型TRIM38 3'-UTR组、miR-432类似物+野生型TRIM38 3'-UTR组、miR-432无义序列+突变型TRIM38 3'-UTR组及miR-432类似物+突变型TRIM38 3'-UTR组,并应用酶标仪检测各组细胞的荧光素酶活性。n 结果:(1)与n IDH突变型胶质瘤样本相比,n IDH野生型胶质瘤样本中miR-432的表达水平明显降低,差异有统计学意义(n P<0.05)。miR-432低表达组的总生存期较miR-432高表达组明显缩短,差异有统计学意义(n P<0.05)。患者的年龄、肿瘤级别及miR-432表达分组与n IDH野生型胶质瘤患者的总生存期相关(n P0.05)。n IDH野生型胶质瘤样本中miR-432与n TRIM38 mRNA的表达水平呈负相关关系(n r=-0.255,n P=0.018)。(2)与无义序列对照组比较,miR-432类似物组培养第2~5天时的细胞活性明显降低,迁移细胞数目明显减少,n TRIM38 mRNA表达水平明显降低,差异均有统计学意义(n P<0.05)。(3)miR-432类似物+野生型TRIM38 3'-UTR组的荧光素酶活性明显低于miR-432无义序列+野生型TRIM38 3'-UTR组细胞,差异有统计学意义(n P<0.05)。n 结论:miR-432在n IDH野生型胶质瘤组织中表达降低,且与患者的预后不良有关;过表达miR-432能够抑制胶质瘤细胞的增殖迁移能力,这或许与其能特异性结合n TRIM38基因并干扰该基因表达有关。n “,”Objective:To study the correlations of micro RNA (miR)-432 expression with cell proliferation and migration, and tripartite motif containing protein 38 (n TRIM38) gene expression in isocitrate dehydrogenase (n IDH) wild-type glioma, and overall survival (OS) of these patients.n Methods:(1) The miRNA expression microarray data of 198 glioma patients (81 with n IDH mutant, 106 with n IDH wild type and 11 with unknown type) and 5 nontumorous brain tissues (controls) were downloaded from China Glioma Genome Atlas (CGGA); expression differences of miR-432 between n IDH mutant and n IDH wild type glioma subgroups and normal controls were compared. According to the median value of miR-432 expression in n IDH wild-type glioma samples, these patients were divided into miR-432 high expression group (n n=51) and miR-432 low expression group (n n=53), Kaplan-Meier survival analysis was used to compare the OS, univariate and multivariate Cox regression analyses were used to determine the factors influencing OS, and Pearson correlation was used to analyze the relation between miR-432 expression and n TRIM38 gene expression. (2) Human glioma cell line U251 was routinely cultured and divided into nonsense sequence control group and miR-432 mimics group; CCK-8 assay was used to detect the cell viability on the 1n st-5n th d of cultivation; Transwell assay was used to detect the cell migration; quantitative reverse transcription PCR (RT-qPCR) was used to detect the n TRIM38 mRNA expression. (3) According to the binding sites between miR-432 and n TRIM38 gene predicted by miRNA target gene prediction database, the wild-type TRIM38 3'-terminal untranslated region (3'-UTR) and mutant TRIM38 3'-UTR sequences were designed; U251 cells were divided into miR-432 nonsense sequence+wild-type TRIM38 3'-UTR group, miR-432 mimics+wild-type TRIM38 3'-UTR group, miR-432 nonsense sequence+mutant TRIM38 3'-UTR group, and miR-432 mimics+mutant TRIM38 3'-UTR group; the luciferase activity in these 4 groups was detected by microplate assay.n Results:(1) The miR-432 expression in n IDH wild-type glioma was significantly decreased as compared with that in the n IDH mutant one (n P<0.05). The OS of patients in the miR-432 low-expression group was significantly shorter as compared with that in the miR-432 high-expression group (n P<0.05). Age, glioma grading, and miR-432 expression were significantly correlated with OS ofn IDH wild-type glioma patients (n P0.05). The miR-432 andn TRIM38 mRNA expressions in n IDH wild-type glioma samples were negatively correlated (n r=-0.255, n P=0.018). (2) As compared with nonsense sequence control group, miR-432 mimics group had significantly lower cell activity on the 2n rd-5n th d of cultivation, significantly smaller number of migrated cells, and statistically decreased n TRIM38 mRNA expression (n P<0.05). (3) The luciferase activity of cells in the miR-432 mimics+wild-type TRIM38 3'-UTR group was significantly lower than that in the miR-432 nonsense+wild-type TRIM38 3'-UTR group (n P<0.05).n Conclusion:The miR-432 expression is low in n IDH wild-type glioma tissues, and it is associated with poor prognosis of these patients; miR-432 overexpression can inhibit the proliferation and migration of glioma cells, which may be related to its specific binding of n TRIM38 gene and interference the expression of this gene.n