MicroRNA signatures in Helicobacter pylori-infected gastric mucosa

MicroRNA signatures in Helicobacter pylori-infected gastric mucosa
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DOI:
10.1002/ijc.25348
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发表时间:
2011-01-15
影响因子:
6.4
通讯作者:
Kohno, Shigeru
Kohno, Shigeru
中科院分区:
医学1区
文献类型:
--
作者:
Matsushima, Kayoko;Isomoto, Hajime;Kohno, Shigeru

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该研究旨在确定幽门螺杆菌感染胃粘膜中microRNA(miRNA)的表达模式,miRNA是一种主要通过翻译抑制控制基因表达的非编码RNA。使用内镜活检标本,在H。幽门螺杆菌感染的胃粘膜用微阵列检测。采用实时定量逆转录聚合酶链反应(RT-PCR)对差异表达的miRNAs进行定量。评估体外感染模型以监测胃上皮中响应H.幽门。该综合方法揭示了表达谱;在加载的470个人类miRNAs中,55个在H.幽门阳性和阴性受试者。在30种miRNA中表达水平显著降低,而hsa-miRNA-223是定量RT-PCR中唯一过表达的miRNA。8个miRNAs能够区分H. pylori状态,准确度可接受。根据更新的悉尼系统,活动和慢性炎症的Gastrointestinal评分与各种miRNA的表达水平显著相关。用抗H治疗感染。pylori方案恢复了30种miRNAs中14种的表达下降。一些miRNAs的表达水平,包括let-7家族成员,在感染强毒H. pylori菌株携带完整的cag致病岛,包括cagA,但不是同基因突变体。这些结果为miRNA参与H.幽门相关性胃炎cagA可能参与胃上皮中某些miRNA的细胞调节。
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.