MicroRNA-374b promotes the proliferation and differentiation of neural stem cells through targeting Hes1

Biochem Biophys Res Commun. 2018 Sep 5;503(2):593-599. doi: 10.1016/j.bbrc.2018.06.044. Epub 2018 Jun 19.

Abstract

Accumulating evidence has documented that microRNAs (miRNAs) are critical regulators of neural stem cell (NSC) proliferation and differentiation. MiRNA-374b (miR-374b) has been reported to play an important role in regulating various cellular processes, such as proliferation and differentiation. However, whether miR-374b is involved in NSC proliferation and differentiation remains unclear. In this study, we investigated the potential role of miR-374b in regulating NSC proliferation and differentiation to elucidate the underlying molecular mechanism. Our results showed that miR-374b expression was significantly upregulated during NSC differentiation. Functional experiments showed that overexpression of miR-374b promoted NSC proliferation and differentiation to neurons. By contrast, miR-374b inhibition showed the opposite effect. Hairy and enhancer of split 1 (Hes1), a master regulator of neurogenesis, was predicted as a potential target gene of miR-374b by bioinformatics analysis. Dual-luciferase reporter assays showed that miR-374b could directly target the 3'-untranslated region of Hes1. Further experiments showed that miR-374b negatively regulated the mRNA and protein expression of Hes1 in NSCs. Moreover, overexpression of Hes1 significantly reversed the miR-374b overexpression-mediated effect on NSC proliferation and differentiation. In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis.

Keywords: Hes1; Neurogenesis; Neuronal stem cells; miR-374b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Cells, Cultured
  • Gene Expression Regulation, Developmental*
  • Mice
  • MicroRNAs / genetics*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Transcription Factor HES-1 / genetics*
  • Up-Regulation

Substances

  • Hes1 protein, mouse
  • MIRN374b microRNA, mouse
  • MicroRNAs
  • Transcription Factor HES-1