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.
Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression.
环状RNA circ_001621通过吸附miR-578并调节VEGF表达来促进骨肉瘤细胞增殖和迁移
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作者:Ji Xianglu, Shan Liping, Shen Peng, He Ming
| 期刊: | Cell Death & Disease | 影响因子: | 9.600 |
| 时间: | 2020 | 起止号: | 2020 Jan 6; 11(1):18 |
| doi: | 10.1038/s41419-019-2204-y | 研究方向: | 细胞生物学 |
| 疾病类型: | 骨肉瘤 | ||
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