Abstract：
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.
摘要：
骨肉瘤（OS）是儿童和青少年常见的原发性骨肿瘤。环状RNA（circularRNA）-IARS在多种人类肿瘤中充当癌基因。然而,操作系统中的circ-IARS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在OS组织和细胞中表达升高。circ-IARS的表达与临床分期和远处转移密切相关。此外，circ-IARS水平高的OS患者的总生存率降低.此外，沉默Circ-IARS减弱OS细胞增殖和侵袭，但细胞铁性凋亡增强。机械上,circ-IARS靶向miR-188-5p以调节OS细胞中的RAB14表达。此外，circ-IARS敲低抑制OS细胞增殖，入侵,并诱导铁性凋亡，然而,抗miR-188-5p或pcDNA-RAB14共转染消除了这些影响.同时,干扰Circ-IARS减少OS细胞增殖，RAB14（RAS癌基因家族的成员）减少，GPX4和xCT(关键铁凋亡调节因子)在体内的表达。总之,circ-IARS通过miR-188-5p/RAB14促进OS进展。
