胃癌组织中mRNA-375基因高甲基化及其表达的研究

摘要

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.%　　目的：探讨胃癌组织中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miRNA-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.