Circular RNAs (circRNAs) are covalently closed noncoding RNA molecules that play multiple roles in tumorigenesis and metastasis. Ferroptosis is an iron-dependent, regulated form of cell death and has emerged as a promising target for cancer treatment. However, whether and how circRNAs regulate ferroptotic cell death in colorectal cancer (CRC) remains largely unknown. Three circRNA microarrays were used to screen differentially expressed circRNAs in CRC tissues. A series of functional experiments were conducted to investigate the effects of circRNA on CRC cell proliferation, migration and ferroptosis. We found that hsa_circ_0058495 (circRHBDD1), a novel circRNA, was significantly upregulated in colorectal cancer tissues and cells. The expression levels of circRHBDD1 in serum samples were strongly associated with the advancement of CRC. Silencing of circRHBDD1 remarkably suppressed the proliferation and migration of CRC cells in vitro. Moreover, the depletion of circRHBDD1 notably increased ferroptotic cell death and enhanced RSL3-induced ferroptosis in CRC cells. Mechanistically, circRHBDD1 upregulated the expression of stearoyl-CoA desaturase (SCD), a ferroptosis suppressor mediating lipid remodelling, by enhancing the ELAVL1/SCD mRNA interaction. Finally, circRHBDD1 knockdown repressed the tumorigenesis and ferroptosis of CRC cells in vivo. In conclusion, circRHBDD1 facilitates tumour progression and obstructs ferroptosis in CRC by regulating SCD expression in an ELAVL1-dependent manner.

环状RNA（circRNA）是共价闭合的非编码RNA分子，在肿瘤发生和转移中发挥多种作用。铁死亡是一种铁依赖性、受调节的细胞死亡形式，已成为癌症治疗的一个有前景的靶标。然而，circRNA 是否以及如何调节结直肠癌 (CRC) 中的铁死亡细胞死亡仍然很大程度上未知。使用三个circRNA微阵列筛选CRC组织中差异表达的circRNA。进行了一系列功能实验来研究circRNA对CRC细胞增殖、迁移和铁死亡的影响。我们发现hsa_circ_0058495（circRHBDD1）是一种新型circRNA，在结直肠癌组织和细胞中显着上调。血清样本中circRHBDD1的表达水平与CRC的进展密切相关。沉默circRHBDD1可显着抑制体外CRC细胞的增殖和迁移。此外， circRHBDD1的缺失显着增加了 CRC 细胞中的铁死亡细胞死亡并增强了 RSL3 诱导的铁死亡。从机制上讲，circRHBDD1通过增强ELAVL1/ SCD mRNA相互作用来上调硬脂酰辅酶A去饱和酶（SCD）的表达，SCD是一种介导脂质重塑的铁死亡抑制剂。最后，circRHBDD1敲低抑制了体内 CRC 细胞的肿瘤发生和铁死亡。总之，circRHBDD1通过以 ELAVL1 依赖性方式调节 SCD 表达来促进肿瘤进展并阻止 CRC 中的铁死亡。