Abstract
Dysregulation of polyamine metabolism has been associated with the development of many cancers. However, little information has been reported about the associations between elevated extracellular putrescine and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. In this study, the influence of extracellular putrescine on the malignant behavior and EMT of the AGS and MKN-28 cells was investigated, followed by RNA sequencing profiling of transcriptomic alterations and CUT&Tag sequencing capturing H3K27ac variations across the global genome using extracellular putrescine. Our results demonstrated that the administration of extracellular putrescine significantly promoted the proliferation, migration, invasion, and expression of N-cadherin in GC cells. We also observed elevated H3K27ac in MKN-28 cells but not in AGS cells when extracellular putrescine was used. A combination of transcriptomic alterations and genome-wide variations of H3K27ac highlighted the upregulated MAL2 and H3K27ac in its promoter region. Knockdown and overexpression of MAL2 were found to inhibit and promote EMT, respectively, in AGS and MKN-28 cells. We demonstrated that extracellular putrescine could upregulate MAL2 expression by elevating H3K27ac in its promoter region, thus triggering augmented EMT in GC cells.