H. pyloriinfection confers resistance to apoptosis via Brd4-dependentBIRC3eRNA synthesis
Peek, Richard M., Jr.
AffiliationUniv Arizona, Coll Med, Dept Cellular & Molevular Med
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationChen, Y., Sheppard, D., Dong, X., Hu, X., Chen, M., Chen, R., ... & Chen, L. F. (2020). H. pylori infection confers resistance to apoptosis via Brd4-dependent BIRC3 eRNA synthesis. Cell death & disease, 11(8), 1-14.
JournalCELL DEATH & DISEASE
Rights© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractH. pyloriinfection is one of the leading causes of gastric cancer and the pathogenicity ofH. pyloriinfection is associated with its ability to induce chronic inflammation and apoptosis resistance. WhileH. pyloriinfection-induced expression of pro-inflammatory cytokines for chronic inflammation is well studied, the molecular mechanism underlying the apoptosis resistance in infected cells is not well understood. In this study, we demonstrated thatH. pyloriinfection-induced apoptosis resistance in gastric epithelial cells triggered by Raptinal, a drug that directly activates caspase-3. This resistance resulted from the induction of cIAP2 (encoded byBIRC3) since depletion ofBIRC3by siRNA or inhibition of cIAP2 via BV6 reversedH. pylori-suppressed caspase-3 activation. The induction of cIAP2 was regulated byH. pylori-inducedBIRC3eRNA synthesis. Depletion ofBIRC3eRNA decreasedH. pylori-induced cIAP2 and reversedH. pylori-suppressed caspase-3 activation. Mechanistically,H. pyloristimulated the recruitment of bromodomain-containing factor Brd4 to the enhancer ofBIRC3and promotedBIRC3eRNA and mRNA synthesis. Inhibition of Brd4 diminished the expression ofBIRC3eRNA and the anti-apoptotic response toH. pyloriinfection. Importantly,H. pyloriisogeniccagA-deficient mutant failed to activate the synthesis ofBIRC3eRNA and the associated apoptosis resistance. Finally, in primary human gastric epithelial cells,H. pylorialso induced resistance to Raptinal-triggered caspase-3 activation by activating the Brd4-dependentBIRC3eRNA synthesis in a CagA-dependent manner. These results identify a novel function of Brd4 inH. pylori-mediated apoptosis resistance via activatingBIRC3eRNA synthesis, suggesting that Brd4 could be a potential therapeutic target forH. pylori-induced gastric cancer.
NoteOpen access journal
VersionFinal published version
Except where otherwise noted, this item's license is described as © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License.
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