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微小RNA-20b下调缺氧诱导因子-1α并抑制骨肉瘤细胞的增殖和侵袭

MicroRNA-20b Downregulates HIF-1α and Inhibits the Proliferation and Invasion of Osteosarcoma Cells.

作者信息

Liu Ming, Wang Dan, Li Ning

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Oncol Res. 2016;23(5):257-66. doi: 10.3727/096504016X14562725373752.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0dd/7838620/949b0977c457/OR-23-257-g001.jpg

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