MicroRNA-146a negatively regulates PTGS2 expression induced by Helicobacter pylori in human gastric epithelial cells.
BACKGROUND
Helicobacter pylori is a major human pathogenic bacterium in the gastric mucosa, but to date the regulatory mechanism of the H. pylori-induced inflammatory response is not clear. MicroRNAs have recently emerged as key post-transcriptional regulators of gene expression. We have previously reported that miR-146a negatively regulates the H. pylori-induced inflammatory response, but its molecular mechanism is just beginning to be explored. Our aim was to further explore the key targets of miR-146a and its role of regulation in H. pylori infection.


METHODS
The potential targets of miR-146a were screened through bioinformatic approaches and identified by luciferase reporter assays and green fluorescent protein (GFP) repression experiments. Overexpression and inhibition of miR-146a were used to examine the impacts of miR-146a on its target gene, determined by quantitative real-time polymerase chain reaction (PCR) and western blotting.


RESULTS
Prostaglandin endoperoxide synthase 2 (PTGS2) is a target gene of miR-146a, and miR-146a decreased PTGS2 expression by degradation of its mRNA, suggesting that the miR-146a-mediated inhibition is a post-transcriptional event. Furthermore, miR-146a and PTGS2 were significantly increased in H. pylori -infected human gastric epithelial cells. Overexpression of miR-146a resulted in significantly reduced PTGS2 production induced by H. pylori infection.


CONCLUSIONS
These results suggest that miR-146a may be involved in negatively regulating H. pylori-induced PTGS2 expression in human gastric epithelial cells.
The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091, China.
Zhen
Z
Liu
Di
D
Wang
Yongliang
Y
Hu
Guoyong
G
Zhou
Chaohui
C
Zhu
Qi
Q
Yu
Yingchun
Y
Chi
Yingli
Y
Cao
Chiyu
C
Jia
Quanming
Q
Zou
D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D005753:Gastric Mucosa / Q000382:microbiology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D016481:Helicobacter Infections / Q000201:enzymology / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human