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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.
摘要：
多胺代谢的失调与许多癌症的发展有关。然而,关于细胞外腐胺升高与胃癌(GC)细胞上皮-间质转化(EMT)之间相关性的报道很少.在这项研究中,研究了细胞外腐胺对AGS和MKN-28细胞的恶性行为和EMT的影响，然后是转录组改变的RNA测序分析，以及使用细胞外腐胺捕获全球基因组中H3K27ac变异的CUT&Tag测序。我们的结果表明，细胞外腐胺的给药显著促进细胞增殖，迁移,入侵,和N-cadherin在GC细胞中的表达。当使用细胞外腐胺时，我们还在MKN-28细胞中观察到H3K27ac升高，但在AGS细胞中未观察到。H3K27ac的转录组改变和全基因组变异的组合突出了其启动子区域中上调的MAL2和H3K27ac。MAL2的敲低和过表达被发现抑制和促进EMT,分别,在AGS和MKN-28细胞中。我们证明了细胞外腐胺可以通过在其启动子区域升高H3K27ac来上调MAL2的表达，从而在GC细胞中触发增强的EMT。
