Bi Chenxiao, Li Chengyu, Xing Liangxiu, Lu Zixuan, Liu Haiyan, Hu Tao, Wang Bin, Liu Chengxia
Department of Gastroenterology and Institute of Digestive Disease, Binzhou Medical University Hospital Binzhou 256600, Shandong, China.
Department of Immunology, Binzhou Medical University Yantai 264000, Shandong, China.
Am J Cancer Res. 2024 Jun 15;14(6):2805-2822. doi: 10.62347/BEUV4081. eCollection 2024.
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 and H3K27ac in its promoter region. Knockdown and overexpression of were found to inhibit and promote EMT, respectively, in AGS and MKN-28 cells. We demonstrated that extracellular putrescine could upregulate expression by elevating H3K27ac in its promoter region, thus triggering augmented EMT in GC cells.
多胺代谢失调与多种癌症的发生发展有关。然而，关于细胞外腐胺升高与胃癌（GC）细胞上皮-间质转化（EMT）之间的关联，报道的信息较少。在本研究中，我们研究了细胞外腐胺对AGS和MKN-28细胞恶性行为和EMT的影响，随后使用细胞外腐胺对转录组改变进行RNA测序分析，并通过CUT&Tag测序捕获全基因组范围内的H3K27ac变化。我们的结果表明，给予细胞外腐胺可显著促进GC细胞的增殖、迁移、侵袭以及N-钙黏蛋白的表达。当使用细胞外腐胺时，我们还观察到MKN-28细胞中H3K27ac升高，但AGS细胞中未升高。转录组改变与H3K27ac全基因组变化相结合，突出了其启动子区域的上调和H3K27ac。在AGS和MKN-28细胞中，分别发现敲低和过表达可抑制和促进EMT。我们证明，细胞外腐胺可通过提高其启动子区域的H3K27ac来上调表达，从而引发GC细胞中增强的EMT。
