ITRAQ-based Bioinformatics Analysis Reveals the Potential Anticancer Effects of ATP4B in Gastric Cancer

Abstract

Background: Gastric cancer (GC) is one of the major malignancies of gastrointestinal tract. Hydrogen-potassium ATPase beta (ATP4B) gene is aberrantly downexpressed in gastric cancer that is associated with worse disease outcome. The objective of this study was to investigate the biological significance of ATP4B in GC carcinogenesis and development. Methods: The expression level of ATP4B was analyzed via clinical tissues and TCGA database. Then, we overexpressed ATP4B in SGC7901 and utilized isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique validate the ATP4B-regulated proteomics profile alterations. Bioinformatics analysis was performed to evaluate the biological processes of ATP4B in GC. Western blot was used for the verification of significant downstream proteins of ATP4B based on bioinformatics analysis data.Results: We identified 293 differentially expressed proteins between the ATP4B overexpressing and control groups in SGC7901, including 145 upregulated proteins and 148 downregulated proteins. GO enrichment analysis indicated that ATP4B-modulating downstream proteins were primarily related to mitochondria function and metabolism. ATP4B-induced enrichments of biological functions were partly associated with suppressing tumor advancement, illustrating an inhibitory role for ATP4B in the progression of GC. Co-expression interaction network analysis exhibited the significant alterations in p53 and STAT3/NF-κB signaling pathway. Consistently, KEGG pathway analysis showed that DEPs are enriched in cell metabolism and cancer-related signaling pathway. Western blot validated the activation of p53 pathway and the inhibition of NF-κB /CD44 pathway after ATP4B overexpressing in GC cells.Conclusion: ATP4B plays a critical anticancer effect by regulating p53/NF-κΒ/mitochondrial pathway. Our data suggested a novel role and mechanism for ATP4B in GC progression.