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

Lookup NU author(s): Dr Sushma Grellscheid, Dr David Dolan, Dr Darren Daniels, Professor Thomas von Zglinicki

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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 x 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 metadata

Author(s): Holly AC, Grellscheid S, van de Walle P, Dolan D, Pilling LC, Daniels DJ, von Zglinicki T, Ferrucci L, Melzer D, Harries LW

Publication type: Article

Publication status: Published

Journal: Biogerontology

Year: 2015

Volume: 16

Issue: 4

Pages: 423-434

Print publication date: 01/08/2015

Online publication date: 21/02/2015

Acceptance date: 17/02/2015

ISSN (print): 1389-5729

ISSN (electronic): 1573-6768

Publisher: Springer

URL: http://dx.doi.org/10.1007/s10522-015-9560-5

DOI: 10.1007/s10522-015-9560-5

PubMed id: 25700689


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