PRDX5 as a novel binding partner in Nrf2-mediated NSCLC progression under oxidative stress

Abstract

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 H2O2-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.

Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

“…Under oxidative stress after gamma irradiation, Keap1 is inactivated, Nrf2 is stabilized, translocated into the nucleus, where it binds to antioxidant response elements (ARE) and initiates transcription of many antioxidative genes, including NQO1. 57 NQO1 is a cytosolic obligatory 2-electron quinone reductase in mammalian systems. It is highly inducible and plays multiple functions in cellular adaptation to oxidative stress.…”

Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth

“…PRDX5 is a binding partner of NRF-2 that can promote its activation to induce the expression of a group of functionally diverse cytoprotective factors such as heme oxygenase-1 (HO1) to attenuate inflammation. 46 , 47 However, SHK did not alter the protein levels of NRF-2 and HO1, and the translocation of NRF-2 into the nucleus (Supplementary Fig. 6a–c ), which indicated that PRDX5 was not a target protein of SHK.…”

Peroxiredoxin-5 Knockdown Accelerates Pressure Overload-Induced Cardiac Hypertrophy in Mice

“…Prx5, also called PrxV/AOEB166/PMP20/PLP/ACR1, was discovered twenty years ago and is widely expressed in mammalian tissues [ 20 ]. As an important member of the Prxs family, Prx5 plays a central role in redox signal transduction and exhibits high scavenging activity toward oxidative stress [ 16 ] [ 21 ].…”