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AOC1 Contributes to Tumor Progression by Promoting the AKT and EMT Pathways in Gastric Cancer

Authors Xu F, Xu Y, Xiong JH, Zhang JH, Wu J, Luo J, Xiong JP

Received 29 July 2019

Accepted for publication 27 December 2019

Published 10 March 2020 Volume 2020:12 Pages 1789—1798

DOI https://doi.org/10.2147/CMAR.S225229

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Fen Xu,1,2 Yun Xu,3 Jian-Hui Xiong,4 Jing-Hui Zhang,2 Jian Wu,2 Jie Luo,2 Jian-Ping Xiong1

1The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Medical College, Shangrao, Jiangxi, People’s Republic of China; 3ShangRao People’s Hospital, Shangrao, Jiangxi, People’s Republic of China; 4The First Affiliated Hospital of Jiangxi Medical College, Shangrao, Jiangxi, People’s Republic of China

Correspondence: Jian-Ping Xiong
Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China
Email jpxiong@medmail.com.cn

Background: AOC1 is a copper-containing amine oxidase that is responsible for catalyzing the deamination of polyamines, which produces reactive oxygen species. Previous studies have demonstrated that polyamines are involved in the regulation of proliferation, migration, and apoptosis of cells. However, very little is known about the functions and regulatory mechanisms of AOC1 in tumors.
Methods: Based on GEPIA data, we found that AOC1 was significantly upregulated in human gastric cancer tissues. We knocked down AOC1 in human AGS and MKN45 cells using siRNA transfection, then utilized qRT-PCR assay and Western blot to verify the effectiveness of AOC1 knockdown in gastric cancer cells.
Results: Function analysis demonstrated that knockdown of AOC1 inhibited the proliferation, invasion, and migration of human gastric cancer cells. Flow cytometry detection suggested that AOC1 knockdown induced apoptosis in human gastric cancer cells. Mechanism investigation suggested that AOC1 knockdown increased the ratio of Bax/Bcl2 and induced activation of the caspase cascade. Furthermore, the AKT signaling pathway was inactivated when AOC1 was silenced, including downregulated phosphorylation level of AKT and expression of downstream effectors, Cyclin D1, and p70S6K. Finally, we found that knockdown of AOC1 inhibited the epithelial–mesenchymal transition (EMT) in human gastric cancer by increasing the expression of epithelial markers E-cadherin, as well as decreasing mesenchymal marker N-cadherin, SNAIL and Slug.
Conclusion: Our study suggests that AOC1 functions as an oncogene in human gastric cancer by activating the AKT signaling pathway and EMT process and maybe a target of 6-mercaptopurine, which provides new insight in the clinical use of AOC1 in gastric cancer therapy.

Keywords: AOC1, proliferation, invasion and migration, apoptosis, AKT, epithelial-mesenchymal transition

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