骨肉瘤（OS）是儿童和青少年常见的原发性骨肿瘤。环状 RNA (circRNA)-IARS 在多种人类肿瘤中充当癌基因。然而，circ-IARS 在 OS 中的功能尚不清楚。本研究旨在阐明 circ-IARS 在 OS 中的作用和机制。在这项研究中，circ-IARS 表达在 OS 组织和细胞中升高。 circ-IARS表达与临床分期、远处转移密切相关。此外，具有高 circ-IARS 水平的 OS 患者的总生存率降低。此外，沉默 circ-IARS 会削弱 OS 细胞的增殖和侵袭，但会增强细胞铁死亡。从机制上讲，circ-IARS 靶向 miR-188-5p 来调节 OS 细胞中的 RAB14 表达。此外，circ-IARS 敲除抑制 OS 细胞增殖、侵袭和诱导铁死亡，但这些影响通过与抗 miR-188-5p 或 pcDNA-RAB14 共转染而消除。同时，干扰 circ-IARS 可减少 OS 细胞增殖，并减少体内 RAB14（RAS 癌基因家族的成员）、GPX4 和 xCT（关键的铁死亡调节因子）的表达。总之，circ-IARS 通过 miR-188-5p/RAB14 促进 OS 进展。

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.