MicroRNA-130b-5p accelerates the migration and invasion of osteosarcoma via binding to TIMP2

Z.-H. Cheng, C. Luo, Z.-L. Guo

Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. gzlysr@outlook.com

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• Oncology

OBJECTIVE: To elucidate the potential function of microRNA-130b-5p in the progression of osteosarcoma (OS) and the underlying mechanism.

MATERIALS AND METHODS: The relative level of microRNA-130b-5p in OS tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the microRNA-130b-5p level and the pathological characteristics of OS was analyzed by the Chi-square test. The Kaplan-Meier curves were introduced for assessing the survival of OS patients with high expression and low expression of microRNA-130b-5p. The regulatory effects of microRNA-130b-5p on the migratory and invasive abilities of MG63 and U2OS cells were evaluated by the transwell assay. The relative levels of matrix metalloproteinase 2 (MMP2) and MMP9 in OS cells with overexpression or knockdown of microRNA-130b-5p were determined. The binding relationship between microRNA-130b-5p and TIMP2 was verified through the dual-luciferase reporter gene assay. Finally, a series of rescue experiments were performed to uncover the role of microRNA-130b-5p/TIMP2 in the progression of OS.

RESULTS: MicroRNA-130b-5p was upregulated in OS tissues and cell lines. The high expression of microRNA-130b-5p indicated a poor prognosis of OS patients. The overexpression of microRNA-130b-5p accelerated OS cells to migrate and invade. Besides, the relative levels of MMP2 and MMP9 were upregulated in OS cells overexpressing microRNA-130b-5p. TIMP2 was the direct target of microRNA-130b-5p, which was negatively regulated by microRNA-130b-5p. The knockdown of TIMP2 reversed the regulatory effect of microRNA-130b-5p on the migratory and invasive abilities of the OS cells.

CONCLUSIONS: MicroRNA-130b-5p is upregulated in OS. It accelerates the progression of OS via inhibiting TIMP2 level.

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