IDDF2021-ABS-0113 Upregulation of oncogene activin a receptor type i by helicobacter pylori infection promotes gastric intestinal metaplasia via regulating CDX2

Background Activin A receptor type I (ACVR1) is involved in tumorigenesis. However, the underlying molecular mechanisms of ACVR1 in gastric cancer (GC) and its association with Helicobacter pylori (H. pylori) remained unclear. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database were utilized to explore the ACVR1 expression in GC and normal control and its association with survival. The ACVR1 was knocked out using CRISPR/Cas-9, RNA sequencing analysis was performed in AGS cells with ACVR1 knockout and normal control. Functional experiments (CCK-8, colony-forming and transwell assays) were conducted to demonstrate the role of ACVR1 in cell proliferation, invasion and metastasis. ACVR1 and CDX2 were detected in AGS cells cocultured with wild type or cagA- H. pylori strains (7.13 and PMSS1) at different MOIs or times. The CDX2 and key elements of BMP signaling pathway were detected in AGS cells with ACVR1 knockout and normal control. In addition, Immunohistochemistry was performed to detect the ACVR1 and CDX2 expression in gastric samples. Results ACVR1 expression was higher in GC than normal control from TCGA, GEPIA and samples collected from our hospital (P Conclusions Our data indicate that H. pylori infection increases ACVR1 expression, promoting gastric IM via regulating CDX2, which is an essential step in H. pylori carcinogenesis.