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Cancer Gene Ther. 2018 Oct 19. doi: 10.1038/s41417-018-0050-1. [Epub ahead of print]

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

Author information

1
Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Republic of Korea.
2
Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, 05505, Republic of Korea.
3
Disease Model Research Laboratory, Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
4
Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Republic of Korea. ngejeong@gmail.com.
5
Laboratory of Animal Genetic Engineering and Stem Cell Biology, Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju, 63243, Republic of Korea. ngejeong@gmail.com.
6
Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Republic of Korea. taehokwonk@gmail.com.
7
Laboratory of Animal Genetic Engineering and Stem Cell Biology, Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju, 63243, Republic of Korea. taehokwonk@gmail.com.

Abstract

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 stemness. Initially, to explore the stemness characteristics and investigate the association of Prx II with those stemness characteristics, we successfully isolated a stem cell-like population from A549/GR cells. A549/GR CD133+ cells possessed important cancer stemness characteristics, including the abilities to undergo metastasis, angiogenesis, self-renewal, and to express stemness 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 stemness characteristics in vitro and in vivo. Next, we investigate whether miR-122 overexpression was associated with Prx II expression and Prx-II-induced stemness characteristics, we transfected miR-122 into A549/GR CSCs. MiR-122 inhibited A549/GR stemness by downregulating the Hedgehog, Notch, and Wnt/β-catenin pathways. Taken together, our data suggest that Prx II promotes A549/GR stemness, and that targeting Prx II and miR-122 is a potentially viable strategy for anti-cancer-stem cell therapy in GR NSCLCs.

PMID:
30341415
DOI:
10.1038/s41417-018-0050-1

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