Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression
Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression
复制标题
DOI：
10.1038/s41419-019-2204-y
复制
发表时间：
2020-01-06
影响因子：
9
通讯作者：
He, Ming
中科院分区：
文献类型：
--
作者：
Ji, Xianglu;Shan, Liping;He, Ming
靶向血管内皮生长因子（VEGF）依赖性骨肉瘤进展的策略是有限的，尽管在阐明机制方面取得了重要进展。在这里，我们通过circRNA微阵列鉴定了circ_001621作为显著上调的环状RNA（circRNA）之一。我们发现，circ_001621高表达的患者生存时间较短。此外，我们发现了几个潜在的海绵microRNA（miRNA）的circ_001621与环状RNA相互作用组数据库。在候选海绵中，我们阐明了circ_001621和miR-578的关联。此外，我们证明了miR-578直接靶向circ_001621。在功能上，我们建立了实验系统来研究circ_001621/miR-578/VEGF相互作用在体外和体内的影响。结果表明，circ_001621通过分别减弱miR-578对细胞周期蛋白依赖性激酶4（CDK 4）和基质金属肽酶9（MMP 9）的抑制，促进骨肉瘤增殖和迁移。进一步进行裸小鼠实验以评估circ_001621对转移的促进作用。本研究评估了circ_001621促进骨肉瘤进展的机制，并为晚期骨肉瘤提供了新的治疗靶点。
Strategies targeted vascular endothelial growth factor (VEGF)-dependent osteosarcoma progression are limited although important progress has been made in illustrating the mechanisms. Here we identified circ_001621 as one of the significantly upregulated circular RNAs (circRNAs) by circRNAs microarrays. We found that patients with high circ_001621 expression had a shorter survival time. Moreover, we found several potential sponge micro RNAs (miRNA) of circ_001621 with Circular RNA Interactome database. Among the candidate sponge, we elucidated the association of circ_001621 and miR-578. In addition, we demonstrated that miR-578 targeted circ_001621 directly. Functionally, we set up the experimental system to investigate the effects of circ_001621/miR-578/VEGF interaction in vitro and in vivo. Results indicated circ_001621-promoted osteosarcoma proliferation and migration via attenuating the inhibition of cyclin-dependent kinase 4 (CDK4) and matrix metallopeptidase 9 (MMP9) by miR-578, respectively. Nude mice experiment was further performed to estimate the promotion of metastasis by circ_001621. The present study evaluated the mechanisms underlying circ_001621 enhanced osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.