MicroRNA-27b suppresses Helicobacter pylori-induced gastric tumorigenesis through negatively regulating Frizzled7

MicroRNAs (miRNAs) are novel tools for cancer therapy. Frizzled7 (FZD7) is an important co-receptor in the WNT signaling pathway. The WNT signaling pathway is aberrantly activated in Helicobacter pylori (H. pylori)-infected gastric cancer cells. However, the role of FZD7 in H. pylori-induced gastric tumorigenesis remains unknown. In this study, we investigated the potential role of FZD7 in H. pylori-induced gastric tumorigenesis and validated the possibility that targeting of FZD7 by specific miRNA inhibits H. pylori-induced gastric tumorigenesis. First, we found that FZD7 was significantly induced by H. pylori infection in a dose- and time-dependent manner. Knockdown of FZD7 by FZD7 small interfering RNA effectively inhibited H. pylori infection-induced cell proliferation of gastric cancer cells. We found that microRNA-27b (miR-27b) was the predicted miRNA for FZD7 and that miR-27b negatively regulated FZD7 expression by targeting the 3'-untranslated region of FZD7. Furthermore, miR-27b overexpression significantly inhibited H. pylori infection-induced cell proliferation and WNT signaling pathway activation in gastric cancer cells. Restoration of FZD7 expression significantly attenuated the inhibitory effect of miR-27b overexpression on cell proliferation and WNT signaling pathway activation. Collectively, our study suggests that FZD7 triggered by H. pylori infection contributes to the H. pylori infection-induced cell proliferation that links the WNT. Thus, miR-27b may be a promising molecular target for the treatment of the disease.