Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression

Abstract

Ling Chen,1 Li Guo,2 Ziwen Sun,3 Guochun Yang,4 Jing Guo,5 Kai Chen,6 Ruixue Xiao,7 Xigui Yang,1 Lijun Sheng1 1Department of Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Scientific Research and Education, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of Emergency Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 5Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 6The Department of Cardiovascular and Thoracic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 7Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Lijun Sheng Email [email protected]: 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.Keywords: monoamine oxidase A, mitochondrial dysfunction, gastric cancer, glycolysis

Keywords

• monoamine oxidase a
• mitochondrial dysfunction
• gastric cancer
• glycolysis.