CEBPB activates NRF2 to regulate the MAPK pathway through DUSP1 to promote proliferation and antioxidant capacity in ovarian cancer cells

NRF2, a crucial antioxidant transcription factor in ovarian cancer (OC), is closely associated with CEBPB activation. However, the regulatory mechanism of NRF2 by CEBPB in OC remains poorly understood. In this study, we systematically evaluated the malignant behavior of SKOV3 and A2780 cells through comprehensive approaches, including CCK-8 kits, clone formation assays, and flow cytometry analysis. Cellular antioxidant capacity was quantitatively assessed using the DCFH-DA and total-antioxidant capacity (T-AOC) assays. Molecular mechanisms were investigated through multiple experimental approaches: the interaction between NRF2 and the DUSP1 promoter was examined using dual fluorescence reporter assays, while the activation status of CEBPB, NRF2, DUSP1, antioxidant proteins, and MAPK pathway components was analyzed via immunofluorescence and western blotting. Our findings demonstrate that CEBPB overexpression significantly enhanced cellular proliferation, clone formation, cell cycle progression, and antioxidant capacity, while simultaneously reducing apoptosis rates and reactive oxygen species (ROS) levels. Conversely, CEBPB knockdown or NRF2 inhibition produced opposing effects. These results establish that CEBPB-mediated NRF2 activation promotes OC cell proliferation and antioxidant defense mechanisms. Mechanistically, we identified that NRF2 directly binds to the DUSP1 promoter, as confirmed by dual-luciferase reporter assays. NRF2 activation led to upregulation of DUSP1 and phosphorylated ERK1/2 levels, while downregulating JNK and p38 phosphorylation. These findings were further validated in vivo, confirming that CEBPB activates NRF2 to regulate the MAPK pathway through DUSP1, thereby promoting OC cell proliferation and antioxidant capacity. In conclusion, our study reveals a novel regulatory axis in which CEBPB activates NRF2 to regulate the MAPK pathway via DUSP1, driving malignant progression and enhancing antioxidant activity in OC.