MicroRNA-128 regulates the differentiation of rat bone mesenchymal stem cells into neuron-like cells by Wnt signaling.

Bone marrow mesenchymal stem cells (BMSCs) are a source of multipotent stem cells ideally suited for various cell-based therapies. BMSCs can differentiate into neuron-like cells under the appropriate conditions. MicroRNAs are members of a family of noncoding small RNAs that regulate gene expression at the posttranscriptional level, either by inhibiting mRNA translation or by promoting mRNA degradation. MicroRNAs play an important role in the differentiation of BMSCs into neurons. MicroRNA-128, a brain-enriched microRNA, was recently found to be necessary in the neural differentiation of BMSCs. Studies have shown that Wnt signaling pathway is involved in regulating MSC differentiation. Our goal here was to investigate whether microRNA-128 can regulate the differentiation of BMSCs through modulation of Wnt3a, a key component of the Wnt signaling pathway. By means of dual-luciferase reporter assay, we describe for the first time that by binding to a specific site in the 3'-UTR of Wnt3a in BMSCs, downregulated microRNA-128 may lead to the neural differentiation of mesenchymal stem cells. Transfection of microRNA-128 mimic decreased the nerve cell markers and Wnt3a expression levels. On the other hand, the inhibition of microRNA-128 significantly elevated the nerve cell markers as well as the Wnt3a expression levels. This suggests that microRNA-128 acts as an endogenous attenuator of BMSCs differentiation into neurons.