MiR‑329‑3p regulates neural stem cell proliferation by targeting E2F1

Abstract

Neural stem cells (NSCs) are a class of self-renewing and undifferentiated progenitor cells that retain the ability to differentiate to neurons, astrocytes and oligodendrocytes. MicroRNAs (miRNAs) are small noncoding RNAs that serve crucial roles in regulating a number of cellular processes, including cell proliferation, differentiation and apoptosis. Our previous GeneChip data indicated that the expression of miR-329-3p was increased in neurons compared with NSCs. However, whether miRNA-329-3p participates in regulating NSC function remains to be elucidated. In the present study, it was identified that the expression of miR-329-3p was upregulated in NSCs during neuronal differentiation, whereas expression of transcription factor E2F1 (E2F1), a putative target gene of miR-329-3p, was downregulated. Using luciferase reporter assays, it was confirmed that miR‑329‑3p regulated E2F1 expression. As differentiation has been demonstrated to limit the proliferative capacity of NSCs, the effects of miR-329-3p and E2F1 modulation on NSC proliferation were examined. Forced overexpression of miR-329-3p or RNA-mediated silencing of E2F1 inhibited NSC proliferation, and overexpression of miR-329-3p also inhibited E2F1 expression. Notably, ectopic expression of E2F1 reversed the inhibition of NSC proliferation induced by miR-329-3p overexpression. These results indicated that miR-329-3p may serve crucial roles in regulating the proliferation of NSCs, at least in part via inhibition of E2F1 expression. These data improve the understanding of the microRNA-mRNA regulatory network that controls NSC proliferation.