Journal
ONCOTARGETS AND THERAPY
Volume 12, Issue -, Pages 5551-5561Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S201373
Keywords
12-lipoxygenase; EMT; Wnt/beta-catenin signaling pathway; gastric cancer
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Funding
- Key Clinical Specialty Discipline Construction Program of Fujian, China [[2012]149]
- Natural Science Foundation of Fujian Province, China [2015J01476]
- Startup Fund for scientific research, Fujian Medical University [2018QH2024]
- Minimally Invasive Medical Center of Fujian, China [[2017]171]
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Background: 12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear. Methods: The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/beta-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo. Results: Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/beta-catenin signaling pathway. Conclusion: These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/beta-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment.
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