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胃癌中 miR-125b1 的异常甲基化:一项病例对照研究。

Aberrant methylation of miR-125b1 in gastric cancer: A case-control study.

机构信息

Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Rasht, Iran.

Gastrointestinal and Liver Diseases Research Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Rasht, Iran.

出版信息

Neoplasma. 2019 Jul 23;66(4):603-608. doi: 10.4149/neo_2018_180925N716. Epub 2019 Mar 7.

Abstract

Gastric cancer (GC) is a complex heterogeneous process and the molecular mechanisms underlying its initiation or propagation are still not very well characterized. Aberrant gene expression are key features of cancer. DNA methylation in a promoter region is an important epigenetic mechanism for the gene silencing. Here, the impact of DNA methylation in regulating the expression of miR-125b1 is explored. A total of 285 genetically unrelated subjects including 175 healthy controls and a total of 110 GC patients participated in this study. we performed nested methylation-specific polymerase chain reaction (MS-PCR) to evaluate methylation pattern of miR-125b1 promoter and quantitative real-time polymerase chain reaction (qRT-PCR) to determine the RNA expression changes in GC and normal tissues. The frequency of methylated allele was 24.5% in GC cases but only 10% in normal tissues. Statistically significant correlation between CpG dinucleotide methylation of miR-125b1 promoter and increased risk of gastric adenocarcinoma was observed (OR=2.57; 95%CI 1.60-4.13; P=0.0001). In addition, miR-125b1 promoter methylation correlated with tumor location and stages. miR-125b1 expression was much higher in normal tissue compared to cancerous tissue. However, methylation status of the miR-125b1 promoter was not correlated with miR-125b1 expression in cancerous specimens (p<0.05). In conclusion, this is a first report of miR-125b1 promoter methylation in GC. More research is needed to fully elucidate the underlying molecular mechanisms of GC susceptibility.

摘要

胃癌(GC)是一个复杂的异质过程,其起始或发展的分子机制仍不是很清楚。异常的基因表达是癌症的一个关键特征。启动子区域的 DNA 甲基化是基因沉默的重要表观遗传机制。在这里,我们探讨了 DNA 甲基化在调节 miR-125b1 表达中的作用。共有 285 名遗传上无关的受试者,包括 175 名健康对照和 110 名 GC 患者参与了这项研究。我们进行了嵌套甲基化特异性聚合酶链反应(MS-PCR)以评估 miR-125b1 启动子的甲基化模式,并进行了定量实时聚合酶链反应(qRT-PCR)以确定 GC 和正常组织中的 RNA 表达变化。GC 病例中甲基化等位基因的频率为 24.5%,而正常组织中仅为 10%。miR-125b1 启动子 CpG 二核苷酸甲基化与胃腺癌风险增加之间存在统计学显著相关性(OR=2.57;95%CI 1.60-4.13;P=0.0001)。此外,miR-125b1 启动子甲基化与肿瘤位置和分期相关。miR-125b1 在正常组织中的表达明显高于癌组织。然而,miR-125b1 启动子的甲基化状态与癌组织中 miR-125b1 的表达无关(p<0.05)。总之,这是首次报道 GC 中 miR-125b1 启动子甲基化。需要进一步的研究来充分阐明 GC 易感性的潜在分子机制。

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