CircASH1L inhibits ferroptosis and enhances cisplatin resistance by sponging miR-515-5p to regulate cell cycle-related CDCA7/RRM2 in ovarian cancer cells

作者：Feng Lu, Xinru Zou, Longyu Tang, Yijun Yuan, Tianwen He, Bin Su, Ying Tang, Jiang Wang, Kang Liu, Jun Li · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1563869 · 被引用次数：5 · 研究领域：Ferroptosis and cancer prognosis、Circular RNAs in diseases、Cancer-related molecular mechanisms research

Background Platinum chemotherapy, particularly cisplatin, has been the standard treatment for ovarian cancer. However, the development of resistance to cisplatin is a significant challenge during treatment. Circular RNAs (circRNAs) are a class of non-coding RNAs with a circular structure and have been implicated in regulating ferroptosis and chemoresistance. Despite the increasing recognition of circRNAs in cancer progression, the role of circASH1L in ferroptosis and cisplatin resistance in ovarian cancer remains poorly understood. Methods RNA sequencing (RNA-seq) was utilized to identify differentially expressed circRNAs in ovarian cancer cells. Cell survival and invasion were assessed using CCK-8 and transwell assays, while apoptosis, cell cycle progression, and lipid peroxidation were analyzed by flow cytometry. Levels of GSH, MDA, and iron ions were measured using appropriate kits. qRT-PCR and Western blot analyses were performed to evaluate the expression of relevant RNAs and proteins. The clinical relevance of circASH1L/miR-515-5p/CDCA7 axis in ovarian cancer patients was analyzed using public datasets. Molecular interactions were confirmed through dual-luciferase reporter assays, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP). In vivo , the effects of circASH1L on ferroptosis and chemoresistance were evaluated using a xenograft mouse model. Results circASH1L expression was downregulated upon erastin treatment and significantly upregulated in cisplati...