Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Department of Pathology, Minhang Hospital, Fudan University, Shanghai 201199, China.
Cell Signal. 2020 Aug;72:109622. doi: 10.1016/j.cellsig.2020.109622. Epub 2020 Mar 30.
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.
越来越多的证据表明，环状 RNA 是癌症早期诊断和治疗的有潜力的生物标志物或靶标。然而，环状 RNA 在骨肉瘤（OS）中的研究还很有限。在这项研究中，我们发现 circ_ARF3 在骨肉瘤细胞系和肿瘤组织中高度表达。敲低 circ_ARF3 会极大地抑制 OS 细胞的生长，损害细胞集落的形成，并阻止细胞周期从 G1 期向 S 期的过渡。生物信息学分析表明，miR-1299 是 circ_ARF3 的靶标。荧光素酶报告基因检测和生物素标记的 circ_ARF3 下拉实验证实了它们在 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 的靶标。在 OS 细胞中过表达 miR-1299 会降低 CDK6 的表达，并抑制 OS 细胞的生长和细胞周期进程。然而，在存在 circ_ARF3 的情况下，miR-1299 对 CDK6 表达、OS 细胞生长和细胞周期进程的调节作用会受到很大的影响。总的来说，我们的研究表明，在骨肉瘤中，高表达的 circ_ARF3 作为 miR-1299 的海绵，抑制 miR-1299 介导的 CDK6 下调，从而进一步促进骨肉瘤的发病机制。circ_ARF3 可能是未来骨肉瘤治疗的一个潜在靶点。
