MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1.

Abstract

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that the miR-133b expression level was decreased while the Sirt1 mRNA expression level was increased in osteosarcoma tissue and cell lines. A low expression of miR-133b was significantly associated with tumor size, distant metastasis, and advanced clinical stage. In addition, osteosarcoma patients with a low miR-133b expression showed a worse prognosis when compared to those with a high level of miR-133b expression. Thus, we identified Sirt1 as a novel direct target of miR-133b. Overexpression of miR-133b suppressed Sirt1 expression and attenuated cell proliferation and invasion. Forced expression of Sirt1 could partly rescue the inhibitory effect of miR-133b in osteosarcoma cells. Our finding also suggested that the inhibitory effects of the miR-133b/Sirt1 axis on osteosarcoma progression were involved in the Wnt/β-catenin pathway. Taken together, these findings will shed light on the role and mechanism of miR-133b in regulating osteosarcoma cell growth via the miR-133b/Sirt1 axis, and miR-133b may serve as a potential therapeutic target in osteosarcoma in the future.