Circular RNAs (circRNAs) are a class of highly multifunctional single-stranded RNAs that play crucial roles in cancer progression, including osteosarcoma (OS). Circ_0002669, generated from the dedicator of cytokinesis (DOCK) gene, was highly expressed in OS tissues, and negatively correlated with OS patient survival. Elevated circ_0002669 promoted OS cell growth and invasion in vivo and in vitro. By biotin pulldown and mass spectroscopy, we found that circ_0002669 directly bound to MYCBP, a positive regulator of c-myc, to prevent MYCBP from ubiquitin-mediated proteasome degradation. In addition, circ_0002669 interacted with miR-889-3p and served as a miRNA sponge to increase the expression of MYCBP, as determined by luciferase assays and RNA immunoprecipitation. Functional rescue experiments indicated MYCBP acted as a key factor for circ_0002669- and miR-889-3p-regulated OS cell proliferation and migration. Increased expression of c-myc-associated genes, such as CCND1, c-Jun and CDK4, were found in circ_0002669- and MYCBP-overexpressing OS cells. Our data thus provide evidence that circ_0002669 promotes OS malignancy by protecting MYCBP from protein ubiquitination and degradation and blocking miR-889-3p-mediated inhibition of MYCBP expression.

中文翻译：

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Circ_0002669通过直接结合MYCBP和海绵miR-889-3p促进骨肉瘤肿瘤发生

环状 RNA (circRNA) 是一类高度多功能的单链 RNA，在包括骨肉瘤 (OS) 在内的癌症进展中发挥着至关重要的作用。 Circ_0002669由胞质分裂专用基因（DOCK）产生，在OS组织中高表达，与OS患者的生存率呈负相关。 circ_0002669升高可促进OS细胞在体内和体外的生长和侵袭。通过生物素下拉和质谱，我们发现circ_0002669直接与c-myc的正调节因子MYCBP结合，以防止MYCBP被泛素介导的蛋白酶体降解。此外，根据荧光素酶测定和 RNA 免疫沉淀测定，circ_0002669 与 miR-889-3p 相互作用并充当 miRNA 海绵，以增加 MYCBP 的表达。功能拯救实验表明 MYCBP 是 circ_0002669 和 miR-889-3p 调节的 OS 细胞增殖和迁移的关键因素。在 circ_0002669 和 MYCBP 过表达的 OS 细胞中发现 c-myc 相关基因（例如 CCND1、c-Jun 和 CDK4）的表达增加。因此，我们的数据提供了证据，表明 circ_0002669 通过保护 MYCBP 免受蛋白质泛素化和降解以及阻断 miR-889-3p 介导的 MYCBP 表达抑制来促进 OS 恶性肿瘤。