Journal
FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.905230
Keywords
myoferlin; gastric cancer; ROS; metastasis; GSH
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Funding
- Shandong Medicine and Health Science Technology Expansion Plan, China
- [2017WS069]
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Myoferlin is a newly identified oncogene that is associated with tumor metastasis, intracellular ROS production, and energy metabolism. Its function in regulating gastric cancer cell migration and ROS accumulation has not been determined.
ObjectiveIn contrast to normal cells, in which reactive oxygen species (ROS) are maintained in redox equilibrium, cancer cells are characterized by ectopic ROS accumulation. Myoferlin, a newly identified oncogene, has been associated with tumor metastasis, intracellular ROS production, and energy metabolism. The mechanism by which myoferlin regulates gastric cancer cell migration and ROS accumulation has not been determined. MethodsMyoferlin expression, intracellular ROS levels, the ratios of reduced to oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) and migratory ability were measured in gastric cancer cells in vitro and in the TCGA and GEO databases in silico. ResultsMyoferlin was found to be more highly expressed in tumor than in normal tissues of gastric cancer patients, with higher expression of Myoferlin associated with shorter survival time. Myoferlin was associated with significantly higher intracellular ROS levels and enhanced migration of gastric cancer cells. N-acetyl-L-cysteine (NAC), a potent inhibitor of ROS, inhibited Myoferlin-induced ROS accumulation and cell migration. ConclusionsMyoferlin is a candidate prognostic biomarker for gastric cancer and plays an essential role in regulating redox equilibrium and gastric cancer cell migration. Myoferlin may also be a new target for treatment of patients with gastric cancer.
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