Cheng S F, Li L, Wang L M
Emergency Department, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China.
Eur Rev Med Pharmacol Sci. 2015 Feb;19(4):607-13.
Helicobacter pylori (H. pylori) infection is the main cause of gastroduodenal ulcer. The molecular mechanisms that underlying this progress are still not very clear. MicroRNAs (miRNAs) are small noncoding RNAs that function as negative regulator of numerous target genes at posttranscriptional level. miRNAs plays important roles in the development of many infection related diseases. The roles of miRNAs in the development of H. pylori-infected gastroduodenal ulcer haven't been well studied yet.
The miRNA and mRNA profiles in normal gastroduodenal biopsy, H. pylori-infected gastroduodenal biopsy and H. pylori-infected gastroduodenal ulcer biopsy samples were compared and analyzed to identify potential related miRNAs and their target genes. The differential expression of the identified miRNAs and their target gene were validated in an independent set of H. pylori positive gastroduodenal ulcer biopsy samples by immunohistochemistry staining and RT-PCR. Then microRNA mimics were transfected to gastric epithelial cells infected with H. pylori 26695 (cagA+). RT-PCR and Western blotting were performed to confirm the target gene of the identified microRNAs.
The integrative analysis and immunohistochemistry staining validation indicated that miR-155 and miR-146b, as well as their predicted target gene IL6, are up-regulated in H. pylori positive gastroduodenal ulcer. Further experiments in gastric epithelial cells revealed that H. pylori 26695 (cagA+) infection induces IL6 overexpression. But the overexpression of IL6 is weaken due to negative regulation by miR-155 and miR-146b.
This study indicated that the up-regulation of miR-155 and miR-146b decreases H. pylori (cagA+)-introduced IL6 overexpression, which might weaken the cleanup of H. pylori (cagA+) and contributes to ulcer.
幽门螺杆菌（H. pylori）感染是胃十二指肠溃疡的主要病因。这一进程背后的分子机制仍不是很清楚。微小RNA（miRNAs）是小的非编码RNA，在转录后水平作为众多靶基因的负调控因子发挥作用。miRNAs在许多感染相关疾病的发展中起重要作用。miRNAs在幽门螺杆菌感染的胃十二指肠溃疡发展中的作用尚未得到充分研究。
比较并分析正常胃十二指肠活检、幽门螺杆菌感染的胃十二指肠活检和幽门螺杆菌感染的胃十二指肠溃疡活检样本中的miRNA和mRNA谱，以鉴定潜在的相关miRNAs及其靶基因。通过免疫组织化学染色和RT-PCR在一组独立的幽门螺杆菌阳性胃十二指肠溃疡活检样本中验证所鉴定的miRNAs及其靶基因的差异表达。然后将微小RNA模拟物转染到感染幽门螺杆菌26695（cagA+）的胃上皮细胞中。进行RT-PCR和蛋白质印迹以确认所鉴定的微小RNA的靶基因。
综合分析和免疫组织化学染色验证表明，miR-155和miR-146b及其预测的靶基因IL6在幽门螺杆菌阳性胃十二指肠溃疡中上调。在胃上皮细胞中的进一步实验表明，幽门螺杆菌26695（cagA+）感染诱导IL6过表达。但由于miR-155和miR-146b的负调控，IL6的过表达减弱。
本研究表明，miR-155和miR-146b的上调降低了幽门螺杆菌（cagA+）诱导的IL6过表达，这可能会削弱幽门螺杆菌（cagA+）的清除并促成溃疡。
