Pathway analysis of senescence-associated miRNA targets reveals common processes to different senescence induction mechanisms

Lafferty-Whyte, K., Cairney, C.J., Jamieson, N., Oien, K.A. and Keith, W.N. (2009) Pathway analysis of senescence-associated miRNA targets reveals common processes to different senescence induction mechanisms. Biochimica et Biophysica Acta: Molecular Basis of Disease, 1792(4), pp. 341-352. (doi:10.1016/j.bbadis.2009.02.003)

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Abstract

Multiple mechanisms of senescence induction exist including telomere attrition, oxidative stress, oncogene expression and DNA damage signalling. The regulation of the cellular changes required to respond to these stimuli and create the complex senescent cell phenotype has many different mechanisms. MiRNAs present one mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated. In this study we investigated 12 miRNAs previously identified as senescence regulators. Using pathway analysis of their target genes we tested the relevance of miRNA regulation in the induction of senescence. Our analysis highlighted the potential of these senescence-associated miRNAs (SA-miRNAs) to regulate the cell cycle, cytoskeletal remodelling and proliferation signalling logically required to create a senescent cell. The reanalysis of publicly available gene expression data from studies exploring different senescence stimuli also revealed their potential to regulate core senescence processes, regardless of stimuli. We also identified stimulus specific apoptosis survival pathways theoretically regulated by the SA-miRNAs. Furthermore the observation that miR-499 and miR-34c had the potential to regulate all 4 of the senescence induction types we studied highlights their future potential as novel drug targets for senescence induction.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jamieson, Dr Nigel and Oien, Dr Karin and Cairney, Dr Claire and Keith, Professor Nicol
Authors: Lafferty-Whyte, K., Cairney, C.J., Jamieson, N., Oien, K.A., and Keith, W.N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Biochimica et Biophysica Acta: Molecular Basis of Disease
Journal Abbr.:BBA-Mol Basis Dis
ISSN:0925-4439
Published Online:12 February 2009

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