Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression
Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression
复制标题
Hsa-mir-27a 遗传变异通过影响 miR-27a 和靶基因表达而导致胃癌易感性
DOI：
10.1111/j.1349-7006.2010.01667.x
复制
发表时间：
2010-10-01
期刊：
影响因子：
5.7
通讯作者：
Wang, Bin
中科院分区：
文献类型：
--
作者：
Sun, Qingmin;Gu, Haijuan;Wang, Bin
目前提出异常microRNA（miRNA）表达与多种人类癌症相关，并且miRNA基因的常见单核苷酸多态性（SNP）可以影响miRNA的成熟或miRNA介导的转录调控。然而，miRNAs SNP是否改变胃癌易感性仍不清楚。本研究旨在探讨hsa-mir-27 a中一个常见的A/G多态性（rs 895819）在胃癌发生、发展中的作用，并评估rs 895819对miR-27 a及其靶基因Zinc finger and BTB domain containing 10（ZBTB 10）表达的影响。在目前的病例对照研究中，我们发现变异基因型（AG + GG）的受试者相对于AA携带者显示出显著增加的胃癌风险（校正比值比= 1.48，95%置信区间1.06-2.05; P = 0.019）。在老年受试者（年龄> 58岁）、男性、非吸烟者和农村受试者中，风险升高尤其明显。hsa-mir-27 a变异基因型与淋巴结转移显著相关。进一步的功能分析表明，变异基因型可能是导致miR-27 a水平升高和ZBTB 10 mRNA降低的原因。此外，发现ZBTB 10和miR-27 a水平之间呈负相关。总之，我们首次发现hsa-mir-27 a中的一个常见多态性（rs 895819）通过调节miR-27 a和ZBTB 10水平，成为胃癌易感性的重要因素。（Cancer Sci 2010）。
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. (Cancer Sci 2010).