Abstract 4389: HEXIM1 is a negative regulator of H. pylori-induced BIRC3 enhancer RNA

Abstract

Abstract The bacterium Helicobacter pylori inhabits the human stomach and is responsible for a number of pathologies, including being strongly associated with the development of gastric adenocarcinoma. H. pylori inhibits apoptosis in gastric cells, but the mechanism is poorly understood. We investigated how H. pylori inhibits apoptosis using cultured G27-strain H. pylori to stimulate cancer cell lines, and apoptosis was induced with Raptinal. We found that H. pylori induces the transcription of the apoptosis-inhibiting protein cIAP2, and this induction is sufficient to inhibit apoptosis in stimulated cells. We found an enhancer region upstream of the gene that codes for cIAP2 (BIRC3). H. pylori induces expression of RNA from this enhancer, and RNAi treatment targeting this eRNA inhibited induction of the BIRC3 mRNA. Chromatin immunoprecipitation revealed that positive transcription elongation factor b (P-TEFb) is recruited to the enhancer following H. pylori stimulation, and RNA polymerase II is activated. We found that the negative regulator of transcription HEXIM1 inhibits P-TEFb recruitment and eRNA production. HEXIM1 also inhibits BIRC3 mRNA transcription, cIAP2 protein induction and H. pylori's anti-apoptotic effect. Together, these findings indicate that H. pylori inhibits apoptosis induction in cultured cells, and this inhibition is mediated by the induction of BIRC3/cIAP2. H. pylori stimulates the production of RNA from the enhancer region of BIRC3, which is required for the induction of the gene, and the eRNA production is regulated by HEXIM1 and P-TEFb. Citation Format: Donald R. Sheppard. HEXIM1 is a negative regulator of H. pylori-induced BIRC3 enhancer RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4389.