title: MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells.
abstract: CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA.
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. zhuyongliangch@yahoo.com.cn
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Jiang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lou
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ji
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wen
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.forename: Haiying
authors.initials: H
authors.lastname: Tao
authors.forename: Tingting
authors.initials: T
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Caihua
authors.initials: C
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Du
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.forename: Jianshan
authors.initials: J
authors.lastname: Mao
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000502:physiology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D055879:Gene Knock-In Techniques; D016480:Helicobacter pylori / Q000502:physiology*; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D020935:MAP Kinase Signaling System; D008679:Metaplasia / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis; D015533:Transcriptional Activation; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C494112:ELK1 protein, human; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; C574604:MIRN1290 microRNA, human; C552781:MIRN584 microRNA, human; D035683:MicroRNAs; D011994:Recombinant Proteins; C080866:cagA protein, Helicobacter pylori; D050807:ets-Domain Protein Elk-1; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2