Expression profiles of miRNAs during ethanol-induced differentiation of neural stem cells

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that are gaining recognition as important regulators of gene expression with the capability to modulate cellular events. Although miRNAs are involved in a wide range of activities related to the development and differentiation of cells, evidence for miRNAs that control the ethanol-induced differentiation programs of specific neural cell types has been elusive. In this study, we isolated neural stem cells (NSC) from the fore-brains of E14 embryos obtained from pregnant C57/BL6J mice. We used microarray technology to monitor the expression profiles of miRNAs during ethanol-induced differentiation of NSC. Comparison of the miRNA expression profiles of NSC and differentiated NSC showed that the expression levels of 58 miRNAs changed by twofold after differentiation. Among these differentially expressed miRNAs, we confirmed the downregulation of the two miRNAs miR-21 and miR-338-3p and the upregulation of miR-320 by real time RT-PCR. By computational analysis, we identified 48 target genes that are predicted to be regulated by miR-21, miR-338-3p and miR-320 during differentiation. We found that most of these predicted target genes are related to cellular processes, such as apoptosis, neural differentiation, cell cycle, metabolism, cell signaling and development. Finally, our findings may contribute to a better understanding of miRNA-regulated neural differentiation in response to ethanol.