PRDX5 as a novel binding partner in Nrf2-mediated NSCLC progression under oxidative stress
Author(s) -
Xinming Chen,
Xiang Cao,
Weizhang Xiao,
Ben Li,
Qun Xue
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.102605
Subject(s) - oxidative stress , peroxiredoxin , cancer research , small hairpin rna , reactive oxygen species , biology , chemistry , microbiology and biotechnology , biochemistry , apoptosis , gene knockdown , enzyme , peroxidase
Non-small-cell lung cancer (NSCLC) is one of the most common malignant tumors in the world. Reactive oxidative species (ROS) and nuclear factor-related factor 2 (Nrf2) -antioxidant response element (ARE) signal pathway are known to play important roles in the development of NSCLC. In this study, we identified Peroxiredoxin 5 (PRDX5) as a novel binding partner for Nrf2. PRDX5 was significantly increased in human NSCLC specimens and cell lines. Nrf2 interacted with PRDX5 in H 2 O 2 -stimulated NCSLC cells, and the interaction promoted the expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) protein in NSCLC cells. Further, high expression of Nrf2 and PRDX5 were associated with worsened prognosis in patients with NSCLC significantly. Moreover, animal studies showed that the growth of tumors treated with Nrf2 and PRDX5 shRNA was significantly lower than that of the other groups. All these data indicated that overexpressed PRDX5 in NSCLC promoted binding with Nrf2 and enhanced NQO1 expression and NSCLC development. Overall, our studies demonstrated that PRDX5 can be a novel binding partner of Nrf2 in promoting NCSLC development under oxidative stress and provide potential opportunity for improving NSCLC therapy.
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