Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8203-8210. doi: 10.26355/eurrev_201910_19127.
To clarify the role of microRNA-183-5p in the malignant progression of osteosarcoma (OS) and the potential mechanism.
Relative level of microRNA-183-5p in 40 paired OS tissues and matched normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between microRNA-183-5p level and clinical indexes of OS patients was analyzed. By transfection of microRNA-183-5p mimics in SaOS-2 and MG63 cells, changes in proliferation and migration were evaluated. The potential target of microRNA-183-5p was verified by dual-luciferase reporter gene assay. Finally, the biological function of protein kinase B (AKT) in OS progression mediated by microRNA-183-5p was detected.
MicroRNA-183-5p was downregulated in OS tissues compared to controls. Relative to OS patients with high expression of microRNA-183-5p, those with low expression had a higher rate of distant metastasis and lower overall survival. Transfection of microRNA-183-5p mimics attenuated proliferative and migratory abilities of SaOS-2 and MG63 cells. AKT was upregulated in OS and negatively correlated to microRNA-183-5p. Overexpression of AKT could abolish the inhibitory effect of microRNA-183-5p on proliferative and migratory abilities of OS cells.
MicroRNA-183-5p is closely related to distant metastasis and poor prognosis of OS. It suppresses the malignant progression of OS by targeting AKT.
阐明 microRNA-183-5p 在骨肉瘤(OS)恶性进展中的作用及其潜在机制。
采用实时定量聚合酶链反应(qRT-PCR)检测 40 对骨肉瘤组织及其配对正常组织中 microRNA-183-5p 的相对水平。分析 microRNA-183-5p 水平与骨肉瘤患者临床指标的相关性。通过转染 microRNA-183-5p 模拟物在 SaOS-2 和 MG63 细胞中,评估增殖和迁移的变化。通过双荧光素酶报告基因检测验证 microRNA-183-5p 的潜在靶标。最后,检测 microRNA-183-5p 介导的蛋白激酶 B(AKT)在骨肉瘤进展中的生物学功能。
与对照组相比,骨肉瘤组织中 microRNA-183-5p 表达下调。与 microRNA-183-5p 高表达的骨肉瘤患者相比,低表达的患者远处转移率更高,总生存率更低。转染 microRNA-183-5p 模拟物可减弱 SaOS-2 和 MG63 细胞的增殖和迁移能力。AKT 在骨肉瘤中上调,并与 microRNA-183-5p 呈负相关。AKT 的过表达可消除 microRNA-183-5p 对骨肉瘤细胞增殖和迁移能力的抑制作用。
microRNA-183-5p 与骨肉瘤的远处转移和不良预后密切相关。它通过靶向 AKT 抑制骨肉瘤的恶性进展。