Selenoprotein K (SELENOK) is one of the endoplasmic reticulum (ER) proteins that mainly functions in the regulation of ER stress, calcium flux, and antioxidant defense. Reactive oxygen species (ROS) is one of the key indicators 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/glutathione 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.

中文翻译：

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敲低 SELENOK 基因可诱导宫颈癌细胞发生铁死亡。

硒蛋白 K (SELENOK) 是一种内质网 (ER) 蛋白，主要在调节 ER 应激、钙通量和抗氧化防御方面发挥作用。活性氧 (ROS) 是铁死亡的关键指标之一，抑制 SELENOK 会破坏 ROS 平衡，从而可能导致铁死亡。然而，之前没有关于SELENOK通过调节ROS影响铁死亡的机制的研究。在这项研究中，我们报告了 SELENOK 抑制对宫颈癌细胞（HeLa 细胞）的细胞增殖、活力、铁循环相关蛋白、ROS、抗氧化酶和脂质过氧化的影响。结果表明，ROS 水平和铁依赖性脂质过氧化显着增强，而细胞活力和增殖显着下调，并导致 SELENOK 敲低后肿瘤大小显着减小。SELENOK 敲低还导致谷胱甘肽过氧化物酶 4/谷胱甘肽水平急剧下降和 ROS 清除能力下降，并加剧了 HeLa 细胞的铁死亡。我们的研究结果阐明了敲低 SELENOK 可以通过调节铁死亡来缩小肿瘤大小，这可能为治疗宫颈癌提供理论依据。