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AOC1 Contributes to Tumor Progression by Promoting the AKT and EMT Pathways in Gastric Cancer
- Source :
- Cancer Management and Research. 12:1789-1798
- Publication Year :
- 2020
- Publisher :
- Informa UK Limited, 2020.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Gene knockdown
Oncogene
Chemistry
Akt/PKB signaling pathway
Cancer
medicine.disease
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
Tumor progression
030220 oncology & carcinogenesis
Cancer cell
medicine
Cancer research
Epithelial–mesenchymal transition
Protein kinase B
Subjects
Details
- ISSN :
- 11791322
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancer Management and Research
- Accession number :
- edsair.doi...........5cacd97dffd125666cfc7c3bead22b42