Increasing evidence suggests that circular RNAs are emerging biomarkers or targets for early cancer diagnosis and treatment. However, the studies of circular RNA in osteosarcoma (OS) are limited. In this study we found that circ_ARF3 were highly expressed in osteosarcoma cell lines and tumor tissues. Knocking down circ_ARF3 greatly ceased OS cell growth, impaired cell colony formation and halted cell cycle transition from G1 to S phase. Bioinformatic analysis suggested that miR-1299 is the target of circ_ARF3. Luciferase assay and biotin labeled circ_ARF3 pull down assay confirmed their interactions in OS cells. The regulatory roles of circ_ARF3 on miR-1299 was also investigated. Further bioinformatic analysis showed that CDK6 is the target of miR-1299. Overexpressing miR-1299 in OS cells decreased CDK6 expression and arrested OS cell growth and cell cycle progression. However, the roles of miR-1299 in regulating CDK6 expression, OS cell growth and cell cycle progression were greatly impaired in the presence of circ_ARF3. In general, our study demonstrated that in the OS, highly expressed circ_ARF3 acts as a sponge of miR-1299 to inhibit miR-1299 mediated CDK6 downregulation which further promoted OS pathogenesis. circ_ARF3 could be a potential target for OS treatment in the future.

中文翻译：

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circ_ARF3通过海绵miR-1299维持CDK6表达来调节骨肉瘤的发病机制。

越来越多的证据表明，环状 RNA 是早期癌症诊断和治疗的新兴生物标志物或靶标。然而，环状RNA在骨肉瘤（OS）中的研究是有限的。在本研究中，我们发现 circ_ARF3 在骨肉瘤细胞系和肿瘤组织中高表达。敲低 circ_ARF3 极大地停止了 OS 细胞的生长，损害了细胞集落形成并停止了从 G1 期到 S 期的细胞周期过渡。生物信息学分析表明 miR-1299 是 circ_ARF3 的靶标。荧光素酶测定和生物素标记的 circ_ARF3 pull down 测定证实了它们在 OS 细胞中的相互作用。还研究了 circ_ARF3 对 miR-1299 的调节作用。进一步的生物信息学分析表明 CDK6 是 miR-1299 的靶点。在 OS 细胞中过表达 miR-1299 会降低 CDK6 表达并阻止 OS 细胞生长和细胞周期进程。然而，在存在 circ_ARF3 的情况下，miR-1299 在调节 CDK6 表达、OS 细胞生长和细胞周期进程中的作用被大大削弱。总的来说，我们的研究表明，在 OS 中，高表达的 circ_ARF3 充当 miR-1299 的海绵，抑制 miR-1299 介导的 CDK6 下调，从而进一步促进 OS 发病机制。circ_ARF3 可能是未来 OS 治疗的潜在目标。高表达的 circ_ARF3 作为 miR-1299 的海绵，抑制 miR-1299 介导的 CDK6 下调，进一步促进 OS 发病机制。circ_ARF3 可能是未来 OS 治疗的潜在目标。高表达的 circ_ARF3 作为 miR-1299 的海绵，抑制 miR-1299 介导的 CDK6 下调，进一步促进 OS 发病机制。circ_ARF3 可能是未来 OS 治疗的潜在目标。