MiR-205 functions as a tumor suppressor via targeting TGF-α in osteosarcoma.

Osteosarcoma (OS) is the most common primary bone cancer, and it is most prevalent in children and young adults. The prognosis of OS remains poor, and survival of OS reached a plateau. The discovery of microRNAs (miRNAs) provides a new possibility for the early diagnosis and treatment of OS. In this study, we detected the expression level of miR-205 and Transforming growth factor-alpha (TGF-α) in 15 cases of clinical OS tissues and adjacent normal bone tissues. We found that the expression of miR-205 was significantly lower in OS tissues than in normal bone tissues; the expression of TGF-α mRNA was significantly increased in OS tissues than in normal bone tissues, the miR-205 was negatively correlated with TGF-α levels in both OS and normal bone tissues. Functional studies demonstrated that miR-205 significantly decreased the capability of cell proliferation, invasion and migration and induced G0/G1 growth arrest and apoptosis in OS cells. By using bioinformatics analytic tool (Targetscan), the 3'UTR of TGF-α gene was found to be a target of miR-205. Luciferase report assay further confirmed that TGF-α 3'UTR is a direct target of miR-205. We also found that the expression of TGF-α mRNA and protein was significantly down-regulated or up-regulated after miR-205 mimic or miR-205 inhibitor transfection. TGF-α knockdown study further showed that miR-205 regulated cell proliferation, invasion and migration by targeting TGF-α in OS. Enforced expression of TGF-α sufficiently restore the effects of miR-205 on cell proliferation, invasion and migration. In conclusion, our study suggested that miR-205 may function as a tumor suppressor via targeting TGF-α in OS, and the abnormal expression of miR-205 might be a key factor in OS progression.