The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzih, Bengbu, Anhui, China.
Sci Rep. 2024 Sep 30;14(1):22646. doi: 10.1038/s41598-024-72506-9.
Altered cholesterol metabolism has been linked to a poor prognosis in various types of cancer. Cholesterol oxidation can lead to lipid peroxidation, membrane damage, and cell death. Ferroptosis is a regulated form of cell death characterized by the accumulation of lipid peroxides, which significantly inhibits the growth of ovarian cancer cells. SQLE is the primary enzyme responsible for catalyzing cholesterol lipid synthesis and is notably expressed in ovarian cancer tissues and cells. This study aims to investigate the role of squalene monooxygenase (SQLE) in ferroptosis in ovarian cancer. The protein and mRNA expression of SQLE was assessed using qRT-PCR, Western Blot, and immunohistochemistry. The association between SQLE and ferroptosis was demonstrated through analysis of TCGA and GTEx databases, TMT protein sequencing, as well as validation by qRT-PCR, Western Blot, immunofluorescence, ROS detection, and lipid peroxide detection. Animal experiments further confirmed the relationship between SQLE and ferroptosis in ovarian cancer. The protein and mRNA expression of SQLE was found to be upregulated in both ovarian cancer tissues and cell lines. Decreased SQLE expression led to ferroptosis in ovarian cancer cells, thereby increasing their sensitivity to ferroptosis inducers. Our research demonstrates that SQLE is significantly upregulated in both ovarian cancer tissues and cells. The overexpression of SQLE in ovarian cancer may facilitate tumorigenesis by conferring resistance to ferroptosis, thus shedding light on potential novel therapeutic strategies for ovarian cancer.
胆固醇代谢的改变与各种类型癌症的不良预后有关。胆固醇氧化可导致脂质过氧化、膜损伤和细胞死亡。铁死亡是一种受调控的细胞死亡形式,其特征是脂质过氧化物的积累,这显著抑制了卵巢癌细胞的生长。鲨烯单加氧酶(SQLE)是催化胆固醇脂质合成的主要酶,在卵巢癌组织和细胞中表达明显。本研究旨在探讨 SQLE 在卵巢癌铁死亡中的作用。使用 qRT-PCR、Western Blot 和免疫组化评估 SQLE 的蛋白和 mRNA 表达。通过 TCGA 和 GTEx 数据库分析、TMT 蛋白质测序以及 qRT-PCR、Western Blot、免疫荧光、ROS 检测和脂质过氧化物检测验证了 SQLE 与铁死亡之间的关联。动物实验进一步证实了 SQLE 与卵巢癌中铁死亡之间的关系。在卵巢癌组织和细胞系中均发现 SQLE 的蛋白和 mRNA 表达上调。降低 SQLE 表达导致卵巢癌细胞发生铁死亡,从而增加了它们对铁死亡诱导剂的敏感性。我们的研究表明 SQLE 在卵巢癌组织和细胞中均显著上调。卵巢癌中 SQLE 的过表达可能通过赋予铁死亡抗性来促进肿瘤发生,从而为卵巢癌提供了潜在的新的治疗策略。