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Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression.
Cell Death & Disease ( IF 9 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41419-019-2204-y
Xianglu Ji 1 , Liping Shan 2 , Peng Shen 1 , Ming He 1
Affiliation  

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.

中文翻译:

环状RNA circ_001621通过使miR-578海绵化并调节VEGF表达来促进骨肉瘤细胞增殖和迁移。

尽管在阐明机制方面已取得重要进展,但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。在这里,我们确定circ_001621是circRNA微阵列显着上调的环状RNA(circRNA)之一。我们发现,circ_001621高表达的患者生存期较短。此外,我们通过环形RNA相互作用组数据库发现了circ_001621的几种潜在的海绵微RNA(miRNA)。在候选海绵中,我们阐明了circ_001621和miR-578的关联。另外,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以研究circ_001621 / miR-578 / VEGF在体外和体内的相互作用。结果表明,circ_001621通过减缓miR-578对细胞周期蛋白依赖性激酶4(CDK4)和基质金属肽酶9(MMP9)的抑制,促进了骨肉瘤的增殖和迁移。进一步进行裸鼠实验以估计circ_001621促进转移。本研究评估了circ_001621增强骨肉瘤进展的机制,并为晚期骨肉瘤提供了新的治疗靶标。
更新日期:2020-01-06
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