胃癌组织中miRNA-375基因高甲基化及其表达的研究

DNA hypermethylation and expression of microRNA-375 gene in gastric cancer

    摘要
  • 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.

     

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