MicroRNA-194-3p inhibits the metastatic biological behaviors of spinal osteosarcoma cells by the repression of matrix metallopeptidase 9.

Osteosarcoma is the most common primary malignant bone tumor, but only 3%-5% of cases occur in the spine. Spinal osteosarcoma presents a significant challenge, and most patients die in spite of aggressive surgery. MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression. The aim of this study was to investigate the role of miR-194-3p and to identify its potential mechanism in spinal osteosarcoma. Here, spinal osteosarcoma tissues showed down-regulated expression of miR-194-3p compared to adjacent non-tumorous tissues. The level of miR-194-3p was negatively correlated with metastasis in patients with spinal osteosarcoma. MiR-194-3p over-expression in spinal osteosarcoma cells significantly inhibited cell migration and invasion in vitro. Furthermore, mechanistic analyses showed that MMP-9 (matrix metallopeptidase 9) is a direct target of miR-194-3p, and the ectopic expression of miR-194-3p inhibits MMP-9 expression by directly binding to the 3'-untranslated region (3'-UTR) of the MMP-9 gene. In summary, our results demonstrate that miR-194-3p suppresses migration and invasion of spinal osteosarcoma cells by targeting MMP-9, indicating miR-194-3p may serve as a promising novel target for spinal osteosarcoma therapy.

The downregulation of miR­125a­5p functions as a tumor suppressor by directly targeting MMP­11 in osteosarcoma.

Osteosarcoma is one of the most common primary malignant bone cancers in juveniles and adults. Increasingly, reports indicate that microRNAs (miRNAs) may provide novel therapeutic targets for cancer treatment. The aim of the present study was to investigate the expression of miR­125a­5p and to identify its functional significance in osteosarcoma. This indicated that miR­125a­5p was downregulated in osteosarcoma tissue and cell lines using reverse transcription­quantitative polymerase chain reaction. Following transfection with miR­125a­5p mimics or the negative control, cell migration, invasion and epithelial­mesenchymal transition (EMT) assays were conducted in osteosarcoma cells. These results indicated that the overexpression of miR­125a­5p resulted in inhibited osteosarcoma cell migration, invasion and EMT in vitro. Furthermore, mechanistic studies showed that matrix metallopeptidase­11 (MMP­11), was a direct target of miR­125a­5p in osteosarcoma. Taken together, the data demonstrate that miR­125a­5p functions as a tumor suppressor gene and serves an important role in inhibiting osteosarcoma cell migration, invasion and EMT by targeting MMP­11.