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miR-222-3p promotes osteosarcoma cell migration and invasion through targeting TIMP3

Authors Guo J, Liu Q, Li Z, Guo H, Bai C, Wang F

Received 30 May 2018

Accepted for publication 22 October 2018

Published 3 December 2018 Volume 2018:11 Pages 8643—8653

DOI https://doi.org/10.2147/OTT.S175745

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai


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

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