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miRNA-183-5p 通过与 AKT 结合抑制骨肉瘤的恶性进展。

MicroRNA-183-5p suppresses the malignant progression of osteosarcoma via binding to AKT.

机构信息

Department of Joint Surgery and Orthopedic Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8203-8210. doi: 10.26355/eurrev_201910_19127.

DOI:10.26355/eurrev_201910_19127
PMID:31646550
Abstract

OBJECTIVE

To clarify the role of microRNA-183-5p in the malignant progression of osteosarcoma (OS) and the potential mechanism.

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

MicroRNA-183-5p is closely related to distant metastasis and poor prognosis of OS. It suppresses the malignant progression of OS by targeting AKT.

摘要

目的

阐明 microRNA-183-5p 在骨肉瘤（OS）恶性进展中的作用及其潜在机制。

方法

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。

结果

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。

结论

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。

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