ArticleCell death & disease2020
H. pylori infection confers resistance to apoptosis via Brd4-dependent BIRC3 eRNA synthesis.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Loss of UBE3C-mediated PIM2 ubiquitination drives Helicobacter pylori-induced gastritis via JAK2/STAT3 activation.Molecular and cellular biochemistry · 2026Article
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- Aging-related signature stratifies LUAD prognosis and uncovers senescence-induced chemoresistance via NF-κB/RELA activation.Respiratory research · 2025Article
- cPDS Promotes Cell Apoptosis by Reducing the Translational Efficiency of BIRC3 mRNA in HCC.Digestive diseases and sciences · 2025Article
- BIRC3 RNA Editing Modulates Lipopolysaccharide-Induced Liver Inflammation: Potential Implications for Animal Health.International journal of molecular sciences · 2025Article
- Raptinal: a powerful tool for rapid induction of apoptotic cell death.Cell death discovery · 2024Review
- Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage.Particle and fibre toxicology · 2024Article
- Unwelcome guests - the role of gland-associatedFrontiers in oncology · 2023Review
- Review
- miR-21 Targets ASPP2 to Inhibit Apoptosis via CHOP-Mediated Signaling inJournal of oncology · 2023Article
- Regulation of programmed cell death by Brd4.Cell death & disease · 2022Review
- Exploring the potential of eRNAs in cancer immunotherapy.Molecular therapy oncolytics · 2022Article
- Mitochondria supply sub-lethal signals for cytokine secretion and DNA-damage in H. pylori infection.Cell death and differentiation · 2022Article
- Enhancer RNA (eRNA) in Human Diseases.International journal of molecular sciences · 2022Review
- Inflammatory Immune-Associated eRNA: Mechanisms, Functions and Therapeutic Prospects.Frontiers in immunology · 2022Review
- Identification and Functional Characterization of Two Noncoding RNAs Transcribed from Putative Active Enhancers in Hepatocellular Carcinoma.Molecules and cells · 2021Article
- Therapeutic effects, immunogenicity and cytotoxicity of a cell penetrating peptide-peptide nucleic acid conjugate againstIranian journal of microbiology · 2021Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
H. pylori infection is one of the leading causes of gastric cancer and the pathogenicity of H. pylori infection is associated with its ability to induce chronic inflammation and apoptosis resistance. While H. pylori infection-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 that H. pylori infection-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 by BIRC3) since depletion of BIRC3 by siRNA or inhibition of cIAP2 via BV6 reversed H. pylori-suppressed caspase-3 activation. The induction of cIAP2 was regulated by H. pylori-induced BIRC3 eRNA synthesis. Depletion of BIRC3 eRNA decreased H. pylori-induced cIAP2 and reversed H. pylori-suppressed caspase-3 activation. Mechanistically, H. pylori stimulated the recruitment of bromodomain-containing factor Brd4 to the enhancer of BIRC3 and promoted BIRC3 eRNA and mRNA synthesis. Inhibition of Brd4 diminished the expression of BIRC3 eRNA and the anti-apoptotic response to H. pylori infection. Importantly, H. pylori isogenic cagA-deficient mutant failed to activate the synthesis of BIRC3 eRNA and the associated apoptosis resistance. Finally, in primary human gastric epithelial cells, H. pylori also induced resistance to Raptinal-triggered caspase-3 activation by activating the Brd4-dependent BIRC3 eRNA synthesis in a CagA-dependent manner. These results identify a novel function of Brd4 in H. pylori-mediated apoptosis resistance via activating BIRC3 eRNA synthesis, suggesting that Brd4 could be a potential therapeutic target for H. pylori-induced gastric cancer.
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Registered trials
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