Therapeutic Discovery MicroRNA-199 a-3 p Is Downregulated in Human Osteosarcoma and Regulates Cell Proliferation and Migration

microRNAs (miRNA,miR)playan important role in cancer cell growthandmigration;however, thepotential roles of miRNAs in osteosarcoma remain largely uncharacterized. By applying a miRNAmicroarray platform and unsupervised hierarchical clustering analysis, we found that several miRNAs have altered expression levels in osteosarcoma cell lines and tumor tissues when compared with normal human osteoblasts. Three miRNAs, miR-199a-3p, miR-127-3p, and miR-376c, were significantly decreased in osteosarcoma cell lines, whereas miR-151-3p and miR-191 were increased in osteosarcoma cell lines in comparison with osteoblasts. Transfection of precursor miR-199a-3p into osteosarcoma cell lines significantly decreased cell growth and migration, thus indicating that the inhibition effect is associatedwith an increase in theG1-phase and a decrease of the S-phase cell population. In addition, we observed decreasedmTOR and Stat3 expression in miR-199a-3p transfected cells. This study provides new insights formiRNAs in osteosarcoma and suggests thatmiR-199a-3p mayplay a functional role in osteosarcoma cell growth andproliferation. RestoringmiR-199a-3p’s functionmay provide therapeutic benefits in osteosarcoma. Mol Cancer Ther; 10(8); 1337–45. 2011 AACR.