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首页> 外文期刊>Cellular Signalling >circ_ARF3 regulates the pathogenesis of osteosarcoma by sponging miR-1299 to maintain CDK6 expression
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circ_ARF3 regulates the pathogenesis of osteosarcoma by sponging miR-1299 to maintain CDK6 expression

机译:Circ_arf3通过海绵MiR-1299调节骨肉瘤的发病机制,以维持CDK6表达

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摘要

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.
机译:越来越多的证据表明,循环RNA正在出现早期癌症诊断和治疗的生物标志物或目标。然而,骨肉瘤(OS)圆形RNA的研究有限。在该研究中,我们发现Circ_arf3在骨肉瘤细胞系和肿瘤组织中高度表达。敲击Quot_arf3大大释放的OS细胞生长,细胞群形成受损,并且从G1到S相中停止的细胞周期过渡。生物信息分析表明miR-1299是Circ_arf3的目标。荧光素酶测定和Biotin标记的循环循环测定测定证实它们在OS细胞中的相互作用。还研究了CIRC_ARF3对MIR-1299的监管作用。进一步的生物信息分析表明CDK6是miR-1299的靶标。过表达MIR-1299在OS细胞中降低CDK6表达和被捕的OS细胞生长和细胞周期进展。然而,在Circ_arf3存在下,MiR-1299在调节CDK6表达,OS细胞生长和细胞周期进展中的作用大大受损。一般来说,我们的研究证明,在OS中,高表达的Circ_arf3用作miR-1299的海绵,以抑制miR-1299介导的CDK6下调,该下调进一步促进了OS发病机制。 Circ_arf3可能是未来OS治疗的潜在目标。

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