OncoTargets and Therapy (Dec 2018)
miR-222-3p promotes osteosarcoma cell migration and invasion through targeting TIMP3
Abstract
Jianping Guo, Quanxiang Liu, Zengxin Li, Haifeng Guo, Changshuang Bai, Fajia Wang Department of Orthopaedic Surgery, Affiliated Hospital of Beihua University, Jilin 132011, PR China Background: Abnormal expression of miRNAs has been reported in osteosarcoma (OS), and miR-222-3p levels have been found to be increased in the serum of OS patients. However, the exact role of miR-222-3p in OS remains unclear. In the present study, we aimed to identify the molecular mechanism underlying the role of miR-222-3p in the development of OS. Methods: We examined the expression level of miR-222-3p in OS tissues and OS cells using reverse-transcription quantitative PCR (RT-qPCR) analysis. MTT, colony formation, and transwell invasion assays were used to analyze the effects of miR-222-3p on the proliferation and invasion ability of OS cells. Luciferase reporter gene assays were used to confirm the target gene of miR-222-3p in OS cells. Tumor xenografts were then used to investigate the role of miR-222-3p in OS growth in vivo. Results: The data of the present study demonstrated that miR-222-3p levels were increased in OS tissues and OS cells. Downregulation of miR-222-3p significantly inhibited the proliferation, migration, and invasion of OS cells in vitro. Further analysis revealed that tissue inhibitors of metalloproteinases 3 (TIMP3) is one of the functional target genes of miR-222-3p, and inhibition of TIMP3 efficiently rescues the blocking of cell proliferation and invasion mediated by miR-222-3p inhibitor in OS cells. Conclusion: Our findings constitute evidence that miR-222-3p promotes OS cell proliferation and invasion through targeting TIMP3 mRNA and provide novel insight into the mechanism underlying the development of OS. Keywords: microRNA-222-3p, osteosarcoma, tissue inhibitor of metalloproteinases 3, migration, invasion
