Down-regulated FDX1 inhibited the proliferation and migration of renal cell carcinoma cells

Abstract

Abstract Background With the intensive study of cell death, a copper-related cell death mechanism has been uncovered that is different from other forms of cell death, which researchers have named cuproptosis. Ferredoxin1 (FDX1) is a key gene in cuproptosis. Available studies have shown that FDX1 expression is down-regulated in a variety of solid tumors and plays an inhibitory role in tumors. However, studies related to the role of FDX1 in renal cell carcinoma (RCC) and its mechanism are scarce and still need to be further explored. Methods Expression spectrum and clinical data obtained from TCGA were used to analyze the differential expression of FDX1 in various types of tumors, the relationship between FDX1 and different clinical features as well as patient survival and prognosis. Immunohistochemical staining experiments were used to verify the difference in FDX1 expression between RCC tissues and normal tissues. RT-qPCR and western blot were carried out to validate the expression of FDX1 between normal renal tubular epithelial cells and RCC cells at the mRNA and protein levels. The effects of FDX1 on the proliferation and migration ability of RCC cells were explored by CCK-8 and scratch assays. Finally, potential signaling pathways involved in FDX1 in RCC were analyzed via Gene Set Enrichment Analysis (GSEA)and subsequently validated using RT-qPCR. Results We found that FDX1 was lowly expressed in RCC tissues and cells, suggesting that FDX1 acts as a protective factor in RCC and that increased expression of FDX1 is favorable to the prognosis of patients. Tumor proliferation and invasive ability were inhibited after the expression of FDX1. In addition, GSEA analysis was significantly enriched in multiple signaling pathways including oxidative phosphorylation. RT-qPCR results indicated that the expression of some important genes in the oxidative phosphorylation pathway was also up-regulated after overexpression of FDX1 in RCC cells. Conclusion Low expression of FDX1 in RCC is associated with poor patient survival. Overexpression of FDX1 may be involved in inhibiting the proliferation and migration of RCC cells through the oxidative phosphorylation pathway.