骨肉瘤（OS）是一种恶性程度较高的间叶肿瘤之一，主要发生在儿童和青少年的长骨干骺端和膝关节周围。OS患者的诊断困难主要归因于早期缺乏明显的临床症状，尽管肿瘤逐渐生长导致严重疼痛和全身症状。OS发病机制尚未完全明确。因此，在OS管理中，早期诊断生物标志物和参与OS进展的新靶点的鉴定具有重要意义。环状RNA（circRNA）是一类具有闭环结构和增强稳定性的非编码RNA，参与细胞增殖、分化、迁移和凋亡的调控。此外，circRNA在衰老和慢性疾病（如癌症和心血管疾病）中也起着重要作用。因此，我们报道了OS组织和细胞系中circRNA-CIRH1A的上调。沉默OS细胞系（U2OS，HOS，Saos-2和MG-63）中的circRNA-CIRH1A会抑制细胞增殖、侵袭、迁移和凋亡，这在移植瘤发生小鼠模型中也得到了验证。我们进一步证实，circRNA-CIRH1A通过吸附miR-1276打断了miR-1276对PI3K/AKT和JAK2/STAT3信号通路的影响。综上，我们的研究揭示了circRNA-CIRH1A在OS中的致癌作用，并确定miR-1276/PI3K-AKT和JAK2-STAT3信号轴是circRNA-CIRH1A的重要下游介导因子。© 2023. 作者。

Osteogenic sarcoma (OS), one of the mesenchymal tumors with a high degree of malignancy, mainly occurs in the metaphysis of the long bones and around the knee joints in children and adolescents. The poor diagnosis in patients with OS can be attributed to the lack of early clinical symptoms, although the growth of tumor mass gradually results in severe pain and systemic symptoms. The mechanisms underlying the pathogenesis of OS are not fully understood. Thus, identifying early diagnostic biomarkers and novel targets involved in the progression of OS is of critical significance in the management of OS. CircRNA is a class of non-coding RNAs characterized by the close-loop structure and increased stability, which are implicated in the regulation of cell proliferation, differentiation, migration, and apoptosis. Moreover, circRNAs also play significant roles in aging and chronic disorders, such as cancer and cardiovascular diseases. Accordingly, we reported the upregulation of circRNA-CIRH1A in OS tissues and cell lines. Silencing circRNA-CIRH1A in OS cell lines (U2OS, HOS, Saos-2, and MG-63) could inhibit the cell proliferation, invasion, migration, and apoptosis, which was also validated in xenograft tumorigenesis mouse model. We further demonstrated that circRNA-CIRH1A sponged miR-1276, which subsequently disrupted the effect of miR-1276 on PI3K/AKT and JAK2/STAT3 signaling pathways. Together, our study revealed the oncogenic role of circRNA-CIRH1A in OS, and identified miR-1276/ PI3K-AKT and JAK2-STAT3 signaling axis as the key downstream mediators of circRNA-CIRH1A.© 2023. The Author(s).