MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells

Previously, we demonstrated that Prx II is important for survival of the gefitinib-resistant A549 (A549/GR) cell line, an NSCLC cell line derived by repeated exposure to gefitinib. Therefore, in this study, we used A549/GR cells to investigate the role of Prx II in GR NSCLC sternness. Initially, to explore the sternness characteristics and investigate the association of Prx II with those sternness characteristics, we successfully isolated a stem cell-like population from A549/GR cells. A549/GR CD133(+) cells possessed important cancer sternness characteristics, including the abilities to undergo metastasis, angiogenesis, self-renewal, and to express sternness genes and epithelial-mesenchymal transition (EMT) markers. However, those characteristics were abolished by knocking down Prx II expression. MicroRNA 122 (miR-122) targets Prx II in A549/GR cancer stem cells (CSCs), thereby inhibiting the sternness characteristics in vitro and in vivo. Next, we investigate whether miR-122 overexpression was associated with Prx II expression and Prx-II-induced sternness characteristics, we transfected miR-122 into A549/GR CSCs. MiR-122 inhibited A549/GR sternness by downregulating the Hedgehog, Notch, and Wnt/beta-catenin pathways. Taken together, our data suggest that Prx II promotes A549/GR sternness, and that targeting Prx II and miR-122 is a potentially viable strategy for anti-cancer-stem cell therapy in GR NSCLCs.