از کار انداختن پروکرسیردوکسین 2 توسط گسترش دهنده متیلاسیون ضروری برای مهاجرت و بقای سلول های سرطانی معده Silencing of peroxiredoxin II by promoter methylation is necessary for the survival and migration of gastric cancer cells

INTRODUCTION Gastric cancer is a leading cause of death worldwide, accounting for nearly 1 000 000 new cases annually and 4700 000 deaths in 2014. Moreover, an estimation of 26 370 diagnosed cases of gastric cancer and eventually 10 730 deaths were reported in the United States in 2016.1,2 In most cases, gastric cancer treatment relies on gastrectomy and chemotherapy. However, due to heterogeneity, gastric cancer recurrence rates are relatively high, and re-resection is no longer an available option for patients with metastatic cases.3 Therefore, therapeutics targeting gastric cancer cell metastasis are of clinical significance. Reactive oxygen species (ROS), including hydrogen peroxide (H2O2) and superoxide anion (O2 − ), are generated during cellular metabolism. Excess amounts of ROS damage cellular macromolecules, such as proteins, DNA and membrane lipids.4 However, recently accumulating evidence indicates that a transient increase in H2O2 has a signaling messenger role in cell proliferation and differentiation, for instance, by reversibly inactivating cysteine residues in protein tyrosine phosphatases.5,6 Under normal conditions, ROS levels are homeostatically maintained by cellular antioxidant enzymes, such as catalase, glutathione peroxidase (GPx) and peroxiredoxin (Prx), which are localized in various cellular compartments. In particular, Prx is the latest family of antioxidant enzymes that was initially identified in Saccharomyces cerevisiae as a protein-protecting glutamine synthetase against mixedfunction oxidation systems.7 It was later discovered that Prx contains conserved cysteine residues in its active site and exhibits H2O2-reducing peroxidase activity by coupling exclusively with thioredoxin, thioredoxin reductase and NADPH.8 The main role of Prx in mammalian cells has long been believed to be as an antioxidant system that scavenges for excess cellular ROS. However, more evidence from recent studies has suggested that Prx has regulatory roles in diverse cancer cell activities, such as proliferation, migration and