Circular RNA_CNST Promotes the Tumorigenesis of Osteosarcoma Cells by Sponging miR-421.
Circular RNA_CNST Promotes the Tumorigenesis of Osteosarcoma Cells by Sponging miR-421.
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DOI：
10.1177/0963689720926147
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发表时间：
2020-01
影响因子：
3.3
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Wang JH;Wu XJ;Duan YZ;Li F
环状RNA（circRNA）在包括骨肉瘤（OS）在内的多种恶性肿瘤的进展中起关键作用。但是，hsa_circ_0017311（circCNST）促进OS肿瘤发生的潜在机制仍知之甚少。本研究旨在探讨circCNST在OS肿瘤发生中的作用及其机制。通过基因表达综合数据库鉴定差异表达的circRNA。通过RNA荧光原位杂交（FISH）和实时定量聚合酶链反应（PCR）分析，分析circCNST与OS患者临床病理特征和预后的关系。进行3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）、集落形成测定和异种移植肿瘤模型以评估circCNST在体外和体内OS细胞中的作用。通过FISH、荧光素酶基因报告和RNA免疫沉淀试验证实了CircCNST与miR-421的特异性结合。因此，我们发现circCNST在OS组织和细胞系中的表达水平与邻近的正常组织相比显著增加，并且其与OS患者的肿瘤大小和较差的存活率相关。敲低circCNST抑制细胞活力、集落形成和异种移植肿瘤生长，而恢复表达circCNST逆转了这些效应。此外，circCNST与miR-421在细胞质中共定位，并充当miR-421的海绵，其通过靶向SLC 25 A3减弱circCNST诱导的OS细胞增殖促进作用。总之，我们的研究结果表明，circCNST通过海绵状miR-421促进OS细胞的肿瘤发生，并为OS患者提供了潜在的生物标志物。
Circular RNAs (circRNAs) act crucial roles in the progression of multiple malignancies including osteosarcoma (OS). But, the underlying mechanisms by which hsa_circ_0017311 (circCNST) contributes to the tumorigenesis of OS remain poorly understood. Our present study aimed to explore the role and mechanisms of circCNST in OS tumorigenesis. The differentially expressed circRNAs were identified by the Gene Expression Omnibus database. The association of circCNST with clinicopathological features and prognosis in patients with OS was analyzed by RNA fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (PCR) analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assays, and a xenograft tumor model were conducted to assess the role of circCNST in OS cells in vitro and in vivo. CircCNST-specific binding with miR-421 was confirmed by FISH, luciferase gene report, and RNA immunoprecipitation assays. As a result, we found that the expression levels of circCNST were dramatically increased in OS tissues and cell lines as compared with the adjacent normal tissues, and it was associated with tumor size and poor survival in OS patients. Knockdown of circCNST repressed cell viability, colony formation, and xenograft tumor growth, while restored expression of circCNST reversed these effects. Furthermore, circCNST was colocalized with miR-421 in the cytoplasm and acted as a sponge of miR-421, which attenuated circCNST-induced proliferation-promoting effects in OS cells by targeting SLC25A3. In conclusion, our findings demonstrate that circCNST promotes the tumorigenesis of OS cells by sponging miR-421, and provides a potential biomarker for patients with OS.
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