Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki, Japan.
Int J Cancer. 2011 Jan 15;128(2):361-70. doi: 10.1002/ijc.25348. Epub 2010 Mar 23.
The study was conducted to determine expression patterns of microRNA (miRNA), a non-coding RNA that controls gene expression mainly through translational repression, in gastric mucosa infected with Helicobacter pylori. Using endoscopic biopsy specimens, miRNA expression patterns in H. pylori-infected gastric mucosa were determined by microarray. The differentially expressed miRNAs were quantitated by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). An in vitro infection model was assessed to monitor the regulation of miRNAs in gastric epithelium in response to H. pylori. The comprehensive method unraveled the expression profiles; among 470 human miRNAs loaded, 55 were differentially expressed between H. pylori-positive and -negative subjects. The expression levels were significantly decreased in 30 miRNAs, whereas hsa-miRNA-223 was the only miRNA to be overexpressed on quantitative RT-PCR. Eight miRNAs enabled discrimination of H. pylori status with acceptable accuracy. Gastritis scores of activity and chronic inflammation according to the updated Sydney system correlated significantly with the expression levels of diverse miRNAs. Cure of the infection with an anti-H. pylori regimen restored decreased expression in 14 of the 30 miRNAs. Expression levels of some miRNAs, including let-7 family members, were significantly altered following infection with a virulent H. pylori strain carrying intact cag pathogenicity island including cagA but not isogenic mutants. These results provide insights into miRNA involvement in the pathogenesis of H. pylori-associated gastritis. cagA may be involved in cellular regulation of certain miRNAs in the gastric epithelium.
本研究旨在确定感染幽门螺杆菌(H. pylori)的胃黏膜中 microRNA(miRNA)的表达模式。miRNA 是一种非编码 RNA,主要通过翻译抑制来控制基因表达。我们通过内镜活检标本,采用微阵列技术确定 H. pylori 感染胃黏膜中的 miRNA 表达模式。采用实时逆转录聚合酶链反应(RT-PCR)定量检测差异表达的 miRNA。通过体外感染模型评估监测胃上皮细胞中 miRNA 对 H. pylori 的调节。综合方法揭示了表达谱;在加载的 470 个人类 miRNA 中,有 55 个在 H. pylori 阳性和阴性受试者之间存在差异表达。30 个 miRNA 的表达水平显著降低,而 hsa-miRNA-223 是唯一在定量 RT-PCR 中过表达的 miRNA。有 8 个 miRNA 可以以可接受的准确度区分 H. pylori 状态。根据更新的悉尼系统,活动性和慢性炎症的胃炎评分与多种 miRNA 的表达水平显著相关。采用抗 H. pylori 方案治愈感染可恢复 30 个 miRNA 中的 14 个下调表达。感染携带完整 cag 致病岛(包括 cagA)但不是同源突变体的毒力 H. pylori 株后,一些 miRNA(包括 let-7 家族成员)的表达水平发生显著改变。这些结果提供了 miRNA 参与 H. pylori 相关胃炎发病机制的见解。cagA 可能参与胃上皮细胞中某些 miRNA 的细胞调节。