Specific downregulation of microRNA-186 induces neural stem cell self-renewal by upregulating Bmi-1/FoxG1 expression.

Abstract

Self-renewal and differentiation in neural stem cells (NSCs) are modulated by microRNAs (miRNAs). However, the recent evidence available is not enough to elucidate the role of miRNA in the self-renewal and differentiation of NSCs from developing brain. In this study, we isolated primary NSCs from the forebrain of fetal rat for in vitro analysis. Downregulation of miRNA-186 in response to a specific miRNA inhibitor resulted in upregulation of Bmi-1 and FoxG1, while maintaining NCS self-renewal. Bmi-1 overexpression restored the maintenance of NSCs in vitro. FoxG1 was found to promote the methylation of Foxo3 promoter and inhibited Foxo3 expression. miR-186 upregulation increased the expression of Foxo3 and inhibited NSC self-renewal in the absence of Foxo3. Therefore, we propose that downregulation of miR-186 maintained NSC self-renewal in the postnatal brain by upregulating the Bmi1/FoxG1 expression via FoxO3 elevation.