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摘要:
目的 探讨胃癌组织中微小RNA-375(miRNA-375)基因表达与基因甲基化调控的相关性。 方法 2011年3月至8月在天津医科大学总医院通过胃镜检查收集90例新鲜组织活检标本, 分为2组, 胃癌组54例, 非癌对照组36例。应用实时荧光定量反转录PCR检测miRNA-375基因表达, 甲基化特异性PCR检测miRNA-375基因启动子区CpG岛甲基化。 结果 胃癌组miR NA-375基因表达下调, 与非癌对照组相比差异有统计学意义(P < 0.05);胃癌组和非癌对照组miRNA-375基因启动子区高甲基化阳性率分别为62.96%(34/54)和22.22%(8/36), 差异有统计学意义(χ2=14.405, P < 0.05)。中高分化胃癌组织中miRNA-375基因表达高于低分化组, 差异有统计学意义(t=2.634, P=0.011);miRNA-375基因启动子区甲基化阳性率中高分化组与低分化组分别为44.44%(8/18)和72.22%(26/36), 差异有统计学意义(χ2=3.971, P=0.046)。 结论 癌组织中存在miRNA-375基因异常低表达及启动子区的高甲基化, miRNA-375基因高甲基化可能抑制miRNA-375基因表达, 在胃癌发生发展中发挥重要作用。 Abstract:Objective This study aimed to explore aberrant DNA methylation of microRNA-375(miRNA-375) gene and its expression in gastric carcinoma tissues. Methods A total of 90 subjects were divided into two groups: gastric carcinoma(n=54) and non-cancer control(n = 36).The expression of miRNA-375 gene was detected by real-time fluorescent quantitative reverse-transcription polymerase chain reaction.The DNA methylation of the CpG island promoters of miRNA-375 was detected by the DNA methylation specific polymerase chain reaction in gastric carcinoma and non-cancer control mucosa. Results The expression of miRNA-375 in the gastric carcinoma significantly decreased compared with the non-cancer control(P=0.000, P < 0.05).The positive rate of the hypermethylation of miRNA-375 gene(62.96%) in the gastric carcinoma was significantly higher than that in the non-cancer control(22.22%)(χ2=14.405, P=0.000, P < 0.05).The expression of miRNA-375 gene in well-differentiated carcinoma was significantly higher than that in poorly differentiated carcinoma.A statistically significant difference was found between the two groups(t=2.634, P=0.011, P < 0.05).The positive rate of DNA hypermethylation of miRNA-375 gene(44.44%, 8/18) in well-differentiated carcinoma was significantly higher than that in poorly differentiated carcinoma(72.22%, 26/36)(χ2=3.971, P=0.046, P < 0.05). Conclusion The aberrant hypermethylation of the CpG island promoters of miRNA-375 gene and their lower expression in gastric carcinoma may play a crucial role in carcinogenesis and gastric carcinoma development. -
Key words:
- stomach neoplasms /
- microRNA /
- gene expression /
- methylation
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图 1 miRNA-375基因甲基化状态检测
Figure 1. miRNA-375 methylation assay
T1, T2, T3:gastric carcinoma tissues; N1, N2:normal gastric mucosa; M: the result of MSP of methylated status; U: the result of MSP of unmethylated status; Ma: Mraker; NE: blank control
表 1 胃癌组及非癌对照组miRNA-375基因的表达
Table 1. Expression of miRNA-375 gene in gastric carcinoma group and non-cancer control group
表 2 miRNA-375基因表达及基因甲基化与胃癌临床病理特征的关系
Table 2. The relationship of miRNA-375 gene expression and methylation with clinicopathological characteristics of gastric cancer
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