MicroRNA-192 inhibits the proliferation, migration and invasion of osteosarcoma cells and promotes apoptosis by targeting matrix metalloproteinase-11

Shang,Guowei; Mi,Yang; Mei,Yingwu; Wang,Guanghui; Wang,Yadong; Li,Xinjie; Wang,Yisheng; Li,Yuebai; Zhao,Guoqiang

doi:10.3892/ol.2018.8239

MicroRNA-192 inhibits the proliferation, migration and invasion of osteosarcoma cells and promotes apoptosis by targeting matrix metalloproteinase-11

Authors:
- Guowei Shang
- Yang Mi
- Yingwu Mei
- Guanghui Wang
- Yadong Wang
- Xinjie Li
- Yisheng Wang
- Yuebai Li
- Guoqiang Zhao
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Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
Published online on: March 12, 2018 https://doi.org/10.3892/ol.2018.8239
Pages: 7265-7272

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Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation and differentiation. miRNAs are also involved in the development and progression of a number of cancer types, including osteosarcoma (OS). miR‑192 is significantly downregulated in various tumors, including lung, bladder and rectal cancer. miR-192 expression is associated with the migration and invasion of OS cells. However, the expression of miR‑192 and its effects on the development of OS have not been reported. In the present study, the involvement of miR‑192 and its molecular mechanisms in the development of OS was investigated. The results indicate that miR‑192 expression was significantly downregulated in OS tissues compared with non‑tumor tissues (P<0.05). Next, a miR‑192 agomir was transfected into the OS cell line MG‑63 to upregulate miR‑192. The effects of miR‑192 overexpression were then investigated by examining cell proliferation, apoptosis, migration and invasion. Matrix metalloproteinase (MMP)‑11 belongs to a family of nine or more highly homologous Zn2+‑endopeptidases. It was demonstrated that the mRNA and protein expression of MMP‑11 were upregulated in OS tissues compared with non‑tumor tissues (P<0.05). MMP‑11 was predicted by TargetScan and miRanda as a miR‑192 target, which was confirmed by western blotting and dual‑luciferase assays. Finally, it was demonstrated that the overexpression of miR‑192 was able to downregulate MMP‑11 expression and reduce proliferation, migration and invasion, and promote apoptosis in OS cells. Together, these data indicate that miR‑192 may be a tumor suppressor that inhibits the progression and invasion of OS by targeting MMP‑11. Therefore, miR‑192 may be useful for the diagnosis and treatment of OS.

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