MicroRNA-141-3p plays a role in human mesenchymal stem cell aging by directly targeting ZMPSTE24

J Cell Sci. 2013 Dec 1;126(Pt 23):5422-31. doi: 10.1242/jcs.133314. Epub 2013 Oct 7.


Human mesenchymal stem cell (hMSC) aging may lead to a reduced tissue regeneration capacity and a decline in physiological functions. However, the molecular mechanisms controlling hMSC aging in the context of prelamin A accumulation are not completely understood. In this study, we demonstrate that the accumulation of prelamin A in the nuclear envelope results in cellular senescence and potential downstream regulatory mechanisms responsible for prelamin A accumulation in hMSCs. We show for the first time that ZMPSTE24, which is involved in the post-translational maturation of lamin A, is largely responsible for the prelamin A accumulation related to cellular senescence in hMSCs. Direct binding of miR-141-3p to the 3'UTR of ZMPSTE24 transcripts was confirmed using a 3'UTR-luciferase reporter assay. We also found that miR-141-3p, which is overexpressed during senescence as a result of epigenetic regulation, is able to decrease ZMPSTE24 expression levels, and leads to an upregulation of prelamin A in hMSCs. This study provides new insights into mechanisms regulating MSC aging and may have implications for therapeutic application to reduce age-associated MSC pool exhaustion.

Keywords: Aging; Histone modification; Mesenchymal stem cells; Prelamin A accumulation; ZMPSTE24; miRNA-141-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cellular Senescence / genetics
  • Epigenesis, Genetic*
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Lamin Type A
  • Luciferases / genetics
  • Luciferases / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Primary Cell Culture
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • Signal Transduction


  • 3' Untranslated Regions
  • Lamin Type A
  • MIRN141 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Nuclear Proteins
  • Protein Precursors
  • prelamin A
  • Luciferases
  • Metalloendopeptidases
  • ZMPSTE24 protein, human