MiR-125b orchestrates cell proliferation, differentiation and migration in neural stem/progenitor cells by targeting Nestin

BMC Neurosci. 2012 Sep 28;13:116. doi: 10.1186/1471-2202-13-116.

Abstract

Background: The emerging concept is that microRNAs (miRNAs) play a central role in controlling stem cell self-renewal and fate determination by regulating the expression of stem cell regulators. miR-125b, one of neuronal miRNAs, recently was found to be necessary for neural differentiation of neural stem/progenitor cells (NS/PCs). However, the other specific biological role of miR-125b in NS/PCs is little known. We used rat NS/PCs as a model system to study the role of miR-125b in governing the behavior of NS/PCs.

Results: We report here the transfection of exogenous miR-125b inhibited proliferation of NS/PCs but promoted differentiation and migration. Whereas anti-miR-125b had the opposite effect. Similar results were observed when Nestin was knocked down by siRNA. Subsequently, we demonstrated that Nestin was a direct functional target of miR-125b. MiR-125b downregulates the expression of luciferase through Nestin 3'untranslated region (3'-UTR), and the regulation was abolished by mutations in the miR-125b binding site. MiR-125b targeted the 3'-UTR of Nestin and reduced the abundance of Nestin at both mRNA and protein levels.

Conclusion: The results provided new insight into the function by which miR-125b modulates NS/PCs proliferation, differentiation and migration. The data also indicated the regulatory role of miR-125b in NS/PCs might through the suppression of Nestin expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Hippocampus / cytology
  • Intermediate Filament Proteins / metabolism*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nestin
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transfection

Substances

  • Intermediate Filament Proteins
  • MicroRNAs
  • Nerve Tissue Proteins
  • Nes protein, rat
  • Nestin
  • RNA, Small Interfering
  • Bromodeoxyuridine