缺氧是癌症进展中不可或缺的因素，并且与沃伯格效应密切相关。环状RNA（CircRNA）因其具有潜在的重要调节因素而在分子恶性肿瘤疗法中引起了极大的关注。然而，circRNA和缺氧在骨肉瘤（OS）进展中的作用尚未阐明。本研究揭示了缺氧敏感的circRNA Hsa_circ_0000566，在低氧应激下对OS进展和能量代谢发挥关键作用。 Hsa_circ_0000566受缺氧诱导因子1α（HIF-1α）调节，并直接结合HIF-1α以及Von Hippel-Lindau（VHL）E3泛素连接酶蛋白。因此，VHL和HIF-1α之间的结合受到阻碍。此外，Hsa_circ_0000566通过与HIF-1α结合（与VHL竞争）并使其免于VHL介导的泛素降解而促进OS进展。这些发现表明由HIF-1α和Hsa_circ_0000566形成的正反馈循环以及它们在OS糖酵解中扮演的关键作用。总之，这些数据表明Hsa_circ_0000566在沃伯格效应中的重要性，并建议Hsa_circ_0000566可能成为对抗OS进展的潜在治疗靶点。copyright: ©2022 Shen等

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.copyright: © 2022 Shen et al.