MicroRNA Changes in Gastric Carcinogenesis: Differential Dysregulation during Helicobacter pylori and EBV Infection

Despite medical advances, gastric-cancer (GC) mortality remains high in Europe. Bacterial infection with Helicobacter pylori (H. pylori) and viral infection with the Epstein-Barr virus (EBV) are associated with the development of both distal and proximal gastric cancer. Therefore, the detection of these infections and the prediction of further cancer development could be clinically significant. To this end, microRNAs (miRNAs) could serve as promising new tools. MiRNAs are highly conserved noncoding RNAs that play an important role in gene silencing, mainly acting via translational repression and the degradation of mRNA targets. Recent reports demonstrate the downregulation of numerous miRNAs in GC, especially miR-22, miR-145, miR-206, miR-375, and miR-490, and these changes seem to promote cancer-cell invasion and tumor spreading. The dysregulation of miR-106b, miR-146a, miR-155, and the Let-7b/c complex seems to be of particular importance during H. pylori infection or gastric carcinogenesis. In contrast, many reports describe changes in host miRNA expression and outline the effects of bamHI-A region rightward transcript (BART) miRNA in EBV-infected tissue. The differential regulation of these miRNA, acting alone or in close interaction when both infections coexist, may therefore enable us to detect cancer earlier. In this review, we focus on the two different etiologies of gastric cancer and outline the molecular pathways through which H. pylori- or EBV-induced changes might synergistically act via miR-155 dysregulation to potentiate cancer risk. The three markers, namely, H. pylori presence, EBV infection, and miR-155 expression, may be checked in routine biopsies to evaluate the risk of developing gastric cancer.

Automated summary

Despite medical advances, gastric-cancer mortality remains high in Europe. Infections with H. pylori and EBV are associated with the development of gastric cancer, and miRNAs could serve as promising new tools for early cancer detection. Dysregulation of specific miRNAs, especially miR-155, may potentiate cancer risk in the presence of these infections.