MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells.

Zhu Y, Jiang Q, Lou X, Ji X, Wen Z, Wu J, Tao H, Jiang T, He W, Wang C, Du Q, Zheng S, Mao J, Huang J
PloS one · 2012 · doi:10.1371/journal.pone.0035147 · PMID:22536353 · PMC3335061
OA: gold CC-BY-4.0
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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.

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SciLite annotations

organisms 54
helicobacter pylori 25 helicobacter pylori 25 candidatus gribaldobacteria bacterium mus sp. helicobacter pylori 25 h 7068019 candidatus gribaldobacteria bacterium mus sp. bradyrhizobium genosp. h mus sp. rodents strain t81213-ntb ] helicobacter pylori 25 transgenic mice zitter rats human mus sp. tequatrovirus t4 tequatrovirus t4 strain u5/41 tequatrovirus t4 strain u5/41 horseradish naine d'afrique de l'ouest rabbits lentivirus lentivirus lentivirus lentivirus mus sp. mus sp. lentivirus lentivirus helicobacter pylori 25 h 7068019 lentivirus mus sp. mus sp. transgenic mice mus sp. mus sp. mus sp. mus sp. h 7068019 helicobacter pylori 25 human mus sp. mus sp. h 7068019 unknown eubacterium human human naine d'afrique de l'ouest rabbits
chemicals 20
tyrosine nucleotide amino acid penicillin streptomycin calcium phosphate spectinomycin ampicillin sodium deoxycholate sodium sulfate polyacrylamide macromolecule nitrocellulose polyfluorene polymer puromycin calcium periodic acid retinoic acid nitrocellulose
body-site 1
MALT)
treatment 24
15% fetal bovine serum (FBS) % FBS cagA/pEGFP-c 1 2 M CaCl 2 G418 (Clontech) -584 -1290 ampicillin polybrene recombinant lentivirus solution Puromycin (5 µg/mL) (Clontech) -1290 -1290 -584 -1290 -584 Foxa 1 shRNA -584 -584 -1290 -584 -1290 -584 -584
host 21
mice mammalian mice mammalian mouse rat human mice mice mice mice Mice mice mouse mice mice mice mice mice mice mice
sample-material 3
gastric tissue tumor tissue samples colon cancer tissue
state 11
Phosphorylated CagA cagA -transgenic -584 -584 -1290 CagA-transformed CagA-transformed Epithelial-mesenchymal Transition (EMT) Foxa 1-silenced -1290 Foxa 1-silenced

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