Monoamine Oxidase A is a Major Mediator of Mitochondria! Homeostasis and Glycolysis in Gastric Cancer Progression
Monoamine Oxidase A is a Major Mediator of Mitochondria! Homeostasis and Glycolysis in Gastric Cancer Progression
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DOI：
10.2147/cmar.s257848
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Sheng, Lijun
中科院分区：
文献类型：
--
作者：
Chen, Ling;Guo, Li;Sheng, Lijun
目的：单胺氧化酶A（MAO-A）是一种线粒体蛋白，参与不同类型肿瘤的发生。然而，MAO-A在胃癌发生发展中的生物学功能仍不清楚。方法：我们检测MAO-A在胃癌组织和胃癌细胞系中的表达，通过免疫组化和Western blot分析。采用CCK-8、流式细胞仪（FACS）和溴脱氧尿苷掺入法检测MAO-A对胃癌细胞增殖的影响。通过MitoSOX Red染色、ATP生成和糖酵解分析，确定MAO-A在线粒体功能中的作用。结果：在本研究中，我们观察到MAO-A在胃癌组织、AGS和MGC 803细胞中显著上调。观察到的MAO-A抑制表明细胞周期进展和增殖降低。MAO-A表达的沉默与胃癌细胞体外迁移和侵袭的抑制有关。此外，线粒体活性氧水平降低和ATP生成增加证明了这些细胞中线粒体损伤的减轻。MAO-A敲低还调节糖酵解限速酶己糖激酶2和丙酮酸脱氢酶的表达。最后，我们观察到，糖酵解介导的作用在AGS和MGC 803细胞减弱时，MAO-A被blocked.Conclusion：本研究的结果表明，MAO-A是负责线粒体功能障碍和有氧糖酵解，这反过来又导致人胃癌细胞的增殖和转移。
Objective: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown.Methods: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays.Results: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked.Conclusion: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.