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

Holly, A.C.; Grellscheid, S.N.; van de Walle, P.; Dolan, D.; Pilling, L.C.; Daniels, D.J.; von Zglinicki, T.; Ferrucci, L.; Melzer, D.; Harries, L.W.

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.

Citation

Holly, A., Grellscheid, S., van de Walle, P., Dolan, D., Pilling, L., Daniels, D., von Zglinicki, T., Ferrucci, L., Melzer, D., & Harries, L. (2015). Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts. Biogerontology, 16, 423–434. https://doi.org/10.1007/s10522-015-9560-5

• Journal Article Type: Article
• Acceptance Date: Feb 17, 2015
• Online Publication Date: Feb 21, 2015
• Publication Date: 2015-08
• Deposit Date: Jun 4, 2015
• Journal: Biogerontology
• Print ISSN: 1389-5729
• Electronic ISSN: 1573-6768
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Pages: 423–434
• DOI: https://doi.org/10.1007/s10522-015-9560-5
• Keywords: Cellular senescence, microRNA, Tissue specificity, Gene expression.
• Public URL: https://durham-repository.worktribe.com/output/1404327