title: MicroRNA-27b suppresses Helicobacter pylori-induced gastric tumorigenesis through negatively regulating Frizzled7.
abstract: 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.
authors.affiliation: Department of Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology and Pathogenic Biology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jiru
authors.initials: J
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology*; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C115810:FZD7 protein, human; D051157:Frizzled Receptors; C531388:MIRN27 microRNA, human; D035683:MicroRNAs