circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4

作者：Yunfei Wang, Taowei Yang, Qihao Li, Zhousan Zheng, Lican Liao, Junjie Cen, Wei Chen, Junhang Luo, Yi Xu, Mi Zhou, Jiaxing Zhang · 发表于：Molecular Cancer · 年份：2025 · DOI：10.1186/s12943-024-02122-8 · 被引用次数：37 · 研究领域：Circular RNAs in diseases、Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression of circular non-coding RNA (circRNA) is associated with poor prognosis in patients with renal clear cell carcinoma (ccRCC), however, the underlying mechanism remains unclear. METHODS: After analysing self-sequenced renal cancer and paracancer circRNA sequencing data and comparing it with the GEO public database, we discovered that circASAP1 expression was significantly up-regulated in renal cancers. We also tested circASAP1 levels in 102 renal cancer patients and found that high expression of circASAP1 was associated with poor prognosis and metastasis. The interaction between circASAP1, HNRNPC and their downstream target genes was confirmed through experiments such as RNA pull-down, RIP and fluorescence in situ hybridisation. A series of in vitro and in vivo functional experiments were performed to verify the effects of circASAP1 on RCC proliferation and metastasis. RESULTS: Circular RNA sequencing analysis revealed that circASAP1 expression was markedly elevated in ccRCC, with a significant association observed between elevated circASAP1 expression and poor prognosis and metastasis. Actinomycin D, RNase R, as well as fluorescence in situ hybridization (FISH) analyses revealed the ring structure and cytoplasmic localization of circASAP1. High circASAP1 expression was associated with ccRCC cell pro...