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

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 Zn ²⁺-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.