Knockdown of the SELENOK gene induces ferroptosis in cervical cancer cells

Abstract

Selenoprotein K (SELENOK) is one of the endoplasmic reticulum(ER) protein that mainly functions in the regulation of endoplasmic reticulum stress (ERS), calcium flux, and antioxidant defense. Reactive oxygen species (ROS) is one of the key indicator of ferroptosis, and SELENOK inhibition could disrupt ROS balance, and consequently might cause ferroptosis. However, there are no previous studies about the mechanism of SELENOK in ferroptosis by regulating ROS. In this study, we report the effect of SELENOK inhibition on cell proliferation, viability, iron recycling-associated proteins, ROS, antioxidant enzymes, and lipid peroxidation of cervical cancer cells (HeLa cells). The results showed that ROS levels and iron-dependent lipid peroxidation were significantly enhanced, whereas cell viability and proliferation were significantly downregulated, and resulted in marked reductions in tumor size after SELENOK knockdown. SELENOK knockdown also caused steep decreases in Glutathione peroxidase 4 (GPX4)/Glutathione (GSH) levels and deterioration in ROS scavenging ability, and exacerbated ferroptosis in HeLa cells. Our findings elucidated that SELENOK knockdown could shrink tumor size by regulating ferroptosis, which might provide a theoretical basis for treating cervical cancer.