The CEBPA/FDX1 axis elevates sensitivity to cuproptosis in lung adenocarcinoma cells

Abstract

Background

The recent introduction of “cuproptosis” into the oncological lexicon has opened up new horizons for cancer therapy, yet our understanding of how this process operates in lung adenocarcinoma (LUAD) is still limited. In this work we have investigated the core genetic factors and provided theoretical support for the application of cuproptosis in the treatment of LUAD. Through bioinformatics analysis, we found that FDX1 was significantly downregulated in LUAD and highly correlated with cuproptosis markers. Therefore, we chose FDX1 as the research object.

Methods

Biochemical and bioinformatic analyses were assessed FDX1 and CEBPA expression in LUAD. The binding relationship between CEBPA and FDX1 was validated via CHIP and dual-luciferase assays. FDX1 expression in LUAD cells was evaluated by qRT-PCR and Western blot. The impact of FDX1 overexpression on LUAD progression was examined using CCK-8 and Transwell assays. Experiments involving CCK-8, copper ion measurement, cuproptosis-related protein detection, and DLAT immunofluorescence confirmed the successful LUAD cuproptosis model.

Results

FDX1 was downregulated in LUAD tissues and cells, and its overexpression inhibited LUAD cell migration, invasion, and proliferation. Cuproptosis significantly reduced LUAD cell viability and the protein levels of Lipoy-DLAT, DLAT, and FDX1, while increasing HSP70 expression, DLAT aggregation, and intracellular copper ion levels. CEBPA, a transcriptional activator of FDX1, positively correlated with and bound to it. Overexpressed FDX1 enhanced cuproptosis in LUAD cells, an effect partially reversible by CEBPA suppression.

Conclusion

These analyses were performed to construct a proposed cellular model of cuproptosis in LUAD.