Biochemical and Biophysical Research Communications, Vol.496, No.3, 806-813, 2018
Methionine sulfoxide reductase B1 regulates proliferation and invasion by affecting mitogen-activated protein kinase pathway and epithelial-mesenchymal transition in u2os cells
Methionine sulfoxide reductase B1 (MsrBl), a member of the selenoprotein family and contributes significantly to the reduction of methionine sulfoxides produced from reactive oxygen species (ROS). However, few studies have examined the role of MsrBl in tumors. Here We tested the proliferation and invasion in MsrBl knockdown u2os cells under H2O2/thioredoxin. As shown in our result, knockdown of MsrBl inhibited the proliferation of u2os cells and regulates mitogen-activated protein kinase (MAPK) pathway by down-regulation of Erk, MeK phosphorylation and p53 expression in u2os cells. In a xenograft tumorigenicity mice, MsrBl knockdown effectively inhibited tumor growth. Furthermore, MsrBl knockdown resulted in migration and invasion reducement of u2os cells. MsrBl regulates epithelial mesenchymal transition (EMT) via affecting cytoskeleton by increasing E-cadherin expression and decreasing N-cadherin, TGF-beta 1, slug, fibronectin, vimentin, c-myc, snail and beta-catenin expressions. In vivo, MsrBl shRNAi can inhibit lung metastasis in metastasis model. In conclusion, MsrBl regulates proliferation and invasion of u2os cells by affecting MAPK pathway and EMT, and MsrBl gene may be a novel therapeutic target against tumors. (C) 2018 Elsevier Inc. All rights reserved.
Keywords:Epithelial-mesenchymal transition;Methionine sulfoxide reductase B1;Mitogen-activated protein kinase pathway;Reactive oxygen species