Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts

Biogerontology. 2015 Aug;16(4):423-34. doi: 10.1007/s10522-015-9560-5. Epub 2015 Feb 21.

Abstract

MicroRNAs are non-coding RNAs with roles in many cellular processes. Tissue-specific miRNA profiles associated with senescence have been described for several cell and tissue types. We aimed to characterise miRNAs involved in core, rather than tissue-specific, senescence pathways by assessment of common miRNA expression differences in two different cell types, with follow-up of predicted targets in human peripheral blood. MicroRNAs were profiled in early and late passage primary lung and skin fibroblasts to identify commonly-deregulated miRNAs. Expression changes of their bioinformatically-predicted mRNA targets were then assessed in both cell types and in human peripheral blood from elderly participants in the InCHIANTI study. 57/178 and 26/492 microRNAs were altered in late passage skin and lung cells respectively. Three miRNAs (miR-92a, miR-15b and miR-125a-3p) were altered in both tissues. 14 mRNA targets of the common miRNAs were expressed in lung and skin fibroblasts, of which two demonstrated up-regulation in late passage skin and lung cells (LYST; p = 0.02 [skin] and 0.02 [lung] INMT; p = 0.03 [skin] and 0.04 [lung]). ZMPSTE24 and LHFPL2 demonstrated altered expression in late passage skin cells only (p = 0.01 and 0.05 respectively). LHFPL2 was also positively correlated with age in peripheral blood (p value = 6.6 × 10(-5)). We find that the majority of senescence-associated miRNAs demonstrate tissue-specific effects. However, miRNAs showing common effects across tissue types may represent those associated with core, rather than tissue-specific senescence processes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / blood
  • Aging / genetics
  • Aging / metabolism*
  • Cell Line
  • Cell Proliferation
  • Cellular Senescence* / genetics
  • Computational Biology
  • Fibroblasts / metabolism*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Humans
  • Lung / cytology
  • Lung / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Skin / cytology
  • Skin / metabolism*
  • Time Factors

Substances

  • MicroRNAs