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

摘要

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-alpha) 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-alpha mRNA was significantly increased in OS tissues than in normal bone tissues, the miR-205 was negatively correlated with TGF-alpha 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 G(0)/G(1) growth arrest and apoptosis in OS cells. By using bioinformatics analytic tool (Targetscan), the 3'UTR of TGF-alpha gene was found to be a target of miR-205. Luciferase report assay further confirmed that TGF-alpha 3'UTR is a direct target of miR-205. We also found that the expression of TGF-alpha mRNA and protein was significantly down-regulated or up-regulated after miR-205 mimic or miR-205 inhibitor transfection. TGF-alpha knockdown study further showed that miR-205 regulated cell proliferation, invasion and migration by targeting TGF-alpha in OS. Enforced expression of TGF-alpha 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-alpha in OS, and the abnormal expression of miR-205 might be a key factor in OS progression. (C) 2015 Elsevier Inc. All rights reserved.