Discovery and characterization of miRNA during cellular senescence in bone marrow-derived human mesenchymal stem cells

Exp Gerontol. 2014 Oct:58:139-45. doi: 10.1016/j.exger.2014.07.020. Epub 2014 Aug 1.

Abstract

Cellular senescence is an irreversible cell cycle arrest in which specific mRNAs and miRNAs are involved in senescence progression. miRNAs interact with specific mRNAs to regulate various cellular mechanisms, including metabolism, proliferation, apoptosis, senescence and differentiation. In this study, we identify and characterize miRNAs during cellular senescence in mesenchymal stem cells (MSCs). Using previously reported miRNAs, expression profiling of 23 miRNAs was performed using real-time PCR analysis. Among these miRNAs, 19 miRNAs showed upregulated expression patterns in senescent MSCs compared with young MSCs, and 5 miRNAs were downregulated. These miRNAs have not been previously identified as being related to cellular senescence but seem to be related. miR-103-2*, miR-140-5p and miR-330-5p are highly upregulated, while miR-29b and miR-199b-5p are significantly downregulated in senescent MSCs. We identify unique functions of 5 miRNAs and predict putative target genes of 5 miRNAs using our previous report. Among them, miR-199b-5p directly suppressed LAMC1 expression, as shown in a luciferase assay. miR-199b-5p significantly regulates translational activity but does not control post-transcriptional activity. Likewise, miR-199b-5p modulates LAMC networks, which demonstrates the resulting phenomenon during cellular senescence, namely, that miR-199b-5p indirectly regulates cellular senescence in MSCs.

Keywords: Cellular senescence; LAMC1; MSC; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellular Senescence*
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Laminin / genetics
  • Laminin / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • Laminin
  • MicroRNAs
  • laminin gamma 1
  • mirn199 microRNA, human