Aberrant microRNA (miRNA) expression is presently proposed to correlate with various human cancers and common single-nucleotide polymorphisms (SNP) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. However, whether miRNAs SNP alter gastric cancer susceptibility is still unclear. Here we investigated the possible role of a common A/G polymorphism (rs895819) within hsa-mir-27a in the development or progression of gastric cancer, and assessed the effect of rs895819 on the expression of miR-27a and its target gene Zinc finger and BTB domain containing 10 (ZBTB10). In the present case-control study, we found that subjects with the variant genotypes (AG + GG) showed a significantly increased risk of gastric cancer relative to AA carriers (adjusted odds ratio = 1.48, 95% confidence interval 1.06-2.05; P = 0.019). The elevated risk was especially evident in older subjects (age >58 years), men, nonsmokers and rural subjects. A significant association of hsa-mir-27a variant genotypes with lymph node metastasis was also observed. Further functional analyses indicated that variant genotypes might be responsible for elevated miR-27a levels and reduced ZBTB10 mRNA. Moreover, an inverse correlation was found between ZBTB10 and miR-27a levels. In conclusion, we were the first to show that a common polymorphism (rs895819) in hsa-mir-27a, by modulating miR-27a and ZBTB10 levels, acted as an important factor of the gastric cancer susceptibility.

译文

:目前提出异常的microRNA(miRNA)表达与各种人类癌症相关,miRNA基因上常见的单核苷酸多态性(SNP)会影响miRNA的成熟或miRNA介导的转录调控。但是,尚不清楚miRNA SNP是否会改变胃癌的易感性。在这里,我们研究了hsa-mir-27a中常见的A / G多态性(rs895819)在胃癌发生或发展中的可能作用,并评估了rs895819对miR-27a及其靶基因Zinc finger表达的影响和包含10的BTB域(ZBTB10)。在本病例对照研究中,我们发现具有变异基因型(AG GG)的受试者相对于AA携带者显示出胃癌的风险显着增加(校正比值比= 1.48,95%置信区间1.06-2.05; P = 0.019 )。在年龄较大的受试者(年龄> 58岁),男性,非吸烟者和农村受试者中,升高的风险尤为明显。还观察到了hsa-mir-27a变异基因型与淋巴结转移的显着相关性。进一步的功能分析表明,变异的基因型可能是导致miR-27a水平升高和ZBTB10 mRNA降低的原因。此外,发现ZBTB10与miR-27a水平呈反相关。总之,我们是第一个显示通过调节miR-27a和ZBTB10水平在hsa-mir-27a中常见的多态性(rs895819),是导致胃癌易感性的重要因素。

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