Liu Ming, Wang Dan, Li Ning
Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Oncol Res. 2016;23(5):257-66. doi: 10.3727/096504016X14562725373752.
Osteosarcoma (OS) is the most common malignant primary bone tumor disease. HIF-1α was predicted to be the target gene of microRNA-20b (miR-20b). The present study was designed to illustrate the effect of miR-20b in regulating osteosarcoma via targeting HIF-1α. In this study, we found that the expression of HIF-1α was significantly increased, while miR-20b obviously decreased in OS patients and OS cell lines compared with healthy controls. Moreover, the luciferase report confirmed the targeting reaction between miR-20b and HIF-1α. Additionally, the overexpression of miR-20b suppressed the invasion and growth of both MG63 and U2OS cells, and inhibited the expressions of HIF-1α and VEGF pathway proteins, while the inhibition of miR-20b led to the reverse results. Furthermore, the overexpression of HIF-1α affected the suppression effect of miR-20b in MG63 cells, indicating that miR-20b suppresses the tumor cell process via inhibiting the expression of HIF-1α. Taken together, our results suggest that the upregulation of miR-20b affects the expression of HIF-1α, downregulates the VEGF pathway proteins, and suppresses cell invasion and proliferation rate. These results provide a potential therapeutic strategy for osteosarcoma.
骨肉瘤（OS）是最常见的原发性恶性骨肿瘤疾病。缺氧诱导因子-1α（HIF-1α）被预测为微小RNA-20b（miR-20b）的靶基因。本研究旨在阐明miR-20b通过靶向HIF-1α对骨肉瘤的调控作用。在本研究中，我们发现与健康对照相比，骨肉瘤患者和骨肉瘤细胞系中HIF-1α的表达显著增加，而miR-20b明显降低。此外，荧光素酶报告实验证实了miR-20b与HIF-1α之间的靶向反应。另外，miR-20b的过表达抑制了MG63和U2OS细胞的侵袭和生长，并抑制了HIF-1α和血管内皮生长因子（VEGF）信号通路蛋白的表达，而抑制miR-20b则导致相反的结果。此外，HIF-1α的过表达影响了miR-20b对MG63细胞的抑制作用，表明miR-20b通过抑制HIF-1α的表达来抑制肿瘤细胞进程。综上所述，我们的结果表明miR-20b的上调影响HIF-1α的表达，下调VEGF信号通路蛋白，并抑制细胞侵袭和增殖率。这些结果为骨肉瘤提供了一种潜在的治疗策略。
