铁死亡是一种新近描述的铁依赖性非凋亡细胞死亡方式，与癌症进展密切相关。然而，在肝细胞癌（HCC）进展期间规避铁死亡的功能和机制仍然未知。在本研究中，我们报道了RNA结合基序单链相互作用蛋白1（RBMS1）参与了HCC的发展，并作为铁死亡的调节因子。临床上，RBMS1在HCC组织中下调，低RBMS1表达与更差的HCC患者生存率相关。机械上，RBMS1过表达通过减弱谷胱甘肽过氧化物酶4（GPX4）的表达抑制了HCC细胞生长，并在体外和体内进一步促进了铁死亡。更重要的是，在HCC细胞中通过海绵miR-19b-3p鉴定了一种新的circIDE（hsa_circ_0000251），提高了RBMS1的表达。总的来说，我们的发现确定了circIDE / miR-19b-3p / RBMS1轴作为铁死亡的调节因子，这可能是一个有前途的治疗靶点和预后因子。

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.