MicroRNA124 Regulated Neurite Elongation by Targeting OSBP

Mol Neurobiol. 2016 Nov;53(9):6388-6396. doi: 10.1007/s12035-015-9540-4. Epub 2015 Nov 18.

Abstract

MicroRNA-124 (miR-124), a brain-specific miRNA molecule, has been implicated in stimulating neurite outgrowth and elongation during neuronal differentiation. However, the direct target genes and the mechanisms of miR-124-induced neurite outgrowth are poorly understood. In this study, we demonstrated that miR-124 directly targeted and downregulated the endogenous expression of oxysterol-binding protein (OSBP). A previous study found that the expression of miR-124 increased during brain development. In the present study, we demonstrated that the expression of OSBP decreased during the development of the C57BL/6 mouse cortex, which was negatively correlated with miR-124 expression. OSBP knockdown using specific shRNAs promoted neurite outgrowth and elongation in both Neuro-2a cells and primary cultured mouse cortical neurons. Conversely, OSBP overexpression strongly repressed the neurite elongation-enhancing effect of miR-124 in Neuro-2a cells. Our results suggested that OSBP may be a target and downstream effector of miR-124 for regulating neurite outgrowth and elongation.

Keywords: Brain development; Neurite elongation; OSBP; miR-124.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Brain / embryology
  • Brain / metabolism
  • Down-Regulation / genetics
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Gene Silencing
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Neurites / metabolism*
  • Neuronal Outgrowth / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, Steroid / metabolism*

Substances

  • MicroRNAs
  • Mirn124 microRNA, mouse
  • RNA, Small Interfering
  • Receptors, Steroid
  • oxysterol binding protein