title: mir-24 activity propagates stress-induced senescence by down regulating DNA topoisomerase 1.
abstract: MicroRNAs (miRNAs) are a group of small non-coding executor RNAs. Their function as key modulators of cellular senescence has been widely recognized recently. By cross-comparing several human aging models we previously identified dozens of miRNAs being differentially regulated during aging. Here the functions of two miRNAs, mir-24 and mir-424, were investigated in an oxidative stress-induced fibroblast premature senescence model. Using pre-miRNA precursors, miRNAs were overexpressed in cells undergoing premature senescence induced by oxidative stress. More senescent cells were observed in mir-24 transfected cells. p53 was upregulated in mir-24 overexpressing cells, but downregulated in mir-424 overexpressing cells. DNA topoisomerase I (TOP1), an enzyme controlling DNA topology, was identified as a target of mir-24, whose expression was induced by oxidative stress. Knocking down TOP1 induced cellular senescence. These results suggest that mir-24 activity propagates stress-induced senescence by down regulating TOP1.
authors.affiliation: Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.
authors.forename: Huajie
authors.initials: H
authors.lastname: Bu
authors.affiliation: Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Baraldo
authors.affiliation: Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria; Department of Cell Biology, University Salzburg, Salzburg, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Lepperdinger
authors.affiliation: Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria. Electronic address: pidder.jansen-duerr@uibk.ac.at.
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D014162:Transfection
chemical_list: C543845:MIRN24 microRNA, human; C554214:MIRN424 microrna, human; D035683:MicroRNAs; D004264:DNA Topoisomerases, Type I
keywords: Cellular senescence; Oxidative stress; TOP1; miRNA; mir-24