1 Background Renal cell carcinoma (RCC) accounts for 2.2% of the total tumor incidence and 1.8% of morbidity worldwide, and its incidence is increasing year by year ( The most important function of VHL is to negatively regulate hypoxia-inducible factor (HIF) to affect fundamental cellular biological processes ( 2 Molecular mechanisms of ferroptosis 2.1 Lipid peroxidation Lipid metabolism is related closely to ferroptosis, and the accumulation of ROS produced by lipid peroxidation in cells is a central step in ferroptosis involving non-enzymatic (i.e., Fenton) reaction pathways ( Exogenous monounsaturated fatty acids (MUFAs) can replace PUFAs on phospholipids located on the cell membrane or other membrane structures, thereby reducing the sensitivity of these membranes to the deactivation of GPX4 and accumulation of ROS ( 2.2 Iron metabolism Iron is involved in many physiological and pathological processes (e.g., ferroptosis and ferritin phagocytosis), while iron homeostasis is strictly regulated to prevent harmful effects on organs caused by iron excess or deficiency ( 2+ and Fe 3+ ( 2+ is absorbed through the intestinal epithelium via divalent metal ion transporter 1 (DMT1) and then transported to the circulation through ferroportin-1 (FPN1) ( 3+ by ceruloplasmin and binds to transferrin (Tf) in the serum ( 3+ is reduced to Fe 2+ by the metalloreductase six-transmembrane epithelial antigen of prostate 3 (STEAP3)
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