miR‐193b promotes cell proliferation by targeting Smad3 in human glioma

Abstract

Studies have shown that several miRNAs play important roles in regulating a variety of cellular processes in gliomas. In these reports, upregulation of miR-193b has been found to be associated with a poor prognosis for glioma, but its functional mechanism in glioma remains unclear. This study investigates the roles of miR-193b in glioma tumor growth. We first showed that the expression of miR-193b was elevated in both glioma samples and glioma cells. Furthermore, downregulation of miR-193b by inhibitors was statistically correlated with a decrease in cell growth and a restored G1 accumulation. Luciferase assay and Western blot analysis revealed that Smad3 is a direct target of miR-193b. To prove that miR-193b regulated cell growth through the transforming growth factor-β (TGF-β) pathway in glioma cells by regulating Smad3, we tested endogenous targets of the TGF-β pathway by measuring the accumulation of p21 mRNAs after downregulation of miR-193b. The results confirmed that induction of p21 was promoted by miR-193b inhibitors in glioma cells, although this induction disappeared when Smad3 was knocked down with siRNA. Moreover, downregulation of Smad3 mitigates the miR-193b suppression of glioma proliferation. In conclusion, these results suggest that miR-193b regulated cell growth in glioma through the TGF-β pathway by regulating Smad3. Thus, our study indicates that miR-193b promotes cell proliferation by targeting Smad3 in human glioma, which may serve as a potentially useful target for development of miRNA-based therapies in the future.