Abstract
Gastric carcinogenesis is associated with alterations of microRNAs (miRNAs) and reversal of these alterations may be a crucial element in cancer prevention. Here we evaluate the influence of H. pylori eradication, low-dose aspirin (LDA), non-steroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPI) on modification of inflammatory mucosal miRNAs miR-155 and miR-223 in Helicobacter pylori-infected and non-infected subjects. The study was performed in two parts: 1) interventional study in 20 healthy subjects with and without H. pylori infection or following eradication (each n = 10) where LDA (100 mg) was given daily for 7 days; 2) prospective case-control observational study (n = 188). MiR-155 and miR-223 expression was strongly linked to H. pylori-infection and in short-term view showed a trend for reversal after eradication. Daily LDA as well as regular NSAIDs showed no influence on miRNAs expression both in healthy subjects and patients, while regular PPI intake was associated with lower miR-155 expression in antrum of patients with chronic gastritis independent of density of neutrophils and mononuclear infiltrate. In summary, PPI but not LDA or NSAIDs were associated with modification of inflammatory miRNAs miR-155 and miR-223 in an H. pylori dependent manner. The functional role of inflammatory miR-155 and miR-223 in understanding of H. pylori-related diseases needs further evaluation.
Highlights
Gastric carcinogenesis consists of a complex multistep multifactorial process related to gender, age, dietary habits, and genetic susceptibility factors as well as environmental influences and microbiota
We studied whether H. pylori-eradication, Non-steroidal anti-inflammatory drugs (NSAIDs), low-dose ASA (LDA)- and pump inhibitors (PPI)-intake influenced the expression pattern of the inflammatory miRNAs miR-155 and miR-223 in the gastric mucosa of healthy subjects with and without H. pylori- gastritis and in patients with various gastric pathologies using a prospective interventional and a case-controls studies, respectively
We evaluated the effect of H. pylori eradication, LDA, NSAIDs and PPI on the expression of two miRNAs that are believed to play an important role in the regulation of inflammatory processes and are deregulated in preneoplastic conditions of the gastric mucosa [8,9,10,11,12,13]
Summary
Gastric carcinogenesis consists of a complex multistep multifactorial process related to gender, age, dietary habits, and genetic susceptibility factors as well as environmental influences and microbiota. Helicobacter pylori (H. pylori)-gastritis is a key factor associated with gastric cancer development [1]. H. pylori colonizes the gastric mucosa, inducing a chronic active gastritis that, in a small percentage of cases, eventually progresses to gastric cancer. According to the Correas cascade [2], ongoing chronic non-atrophic gastritis (CNAG) may result in atrophic. Effect of drugs on microRNA in gastric mucosa “European funds for regional development” (EFRE) as well as by the regional Ministry of Economy, Science and Digitalization as part of the “Autonomie im Alter” research group for “LiLife”Project
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