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| Status |
Public on Jun 08, 2016 |
| Title |
Downregulation of miR-15b is associated with increased SIRT4 expression in premature senescence and photoaging of the skin |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Non-coding RNA profiling by array
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| Summary |
Sirtuins are deacetylases or ADP-ribosyltransferases which are implicated in multiple pathways involved in metabolism and life-span regulation. Here, we link the mitochondrial sirtuin SIRT4, which overexpression negatively impacts on mitochondrial oxidative capacity, with premature senescence and skin aging. Accordingly, SIRT4 mRNA levels were significantly increased in vitro in human dermal fibroblasts after repetitive UVB exposure or in senescence triggered by mitotic spindle stress or ionizing radiation. Similarly, analysis of SIRT4 expression in vivo in human skin revealed upregulation of SIRT4 mRNA levels in the dermal compartment of photaged skin as compared with the dermis of intrinsically aged skin. In all our in vitro models, upregulation of SIRT4 expression was associated with decreased levels of miR-15b.
Also, in human skin, highest copy numbers of miR-15b mRNA were detected in the epidermis, and epidermal expression was significantly reduced in photoaged skin as compared with intrinsically aged skin. Reduced miR-15b expression is most likely causally linked to increased SIRT4 expression because we found that (i) miR-15b displays a conserved and direct binding site within the 3'-untranslated region of the SIRT4 gene as demonstrated by luciferase reporter assays and (ii) transfection of oligonucleotides mimicking miR-15b function was sufficient to prevent SIRT4 upregulation in senescent cells in vitro. Thus, we propose that miR-15b acts as a negative regulator of SIRT4 expression to antagonize mitochondrial dysfunction and hence cellular senescence as well as tissue aging, in particular photoaging of the skin.
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| Overall design |
MCF7 cells were transfected with a control shRNA or Tacc3 shRNA, respectively. The expression of the shRNA were controled via DOX treatment. All experiments were done in 4 independent replicates [GSM1113279-GSM1113290]
The effect of Tacc3 depletion on the expression level of miRNA's were measured [GSM1129017-GSM1129023].
MCF7 breast carcinoma cells were exposed to gammaIR (20 Gy). After irradiation, cells were cultured for 4 and 6 days. The effect of irradiation on the gene expression were measured [GSM1129024-GSM1129031].
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| Contributor(s) |
Kuck F, Lindecke A, Köhrer K, Piekorz RP |
| Citation(s) |
26959556 |
| Submission date |
Apr 03, 2013 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Antje Lindecke |
| E-mail(s) |
antje.lindecke@uni-duesseldorf.de
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| Phone |
49-211-8114367
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| Organization name |
Universitaet Duesseldorf
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| Department |
BMFZ
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| Lab |
Microarray
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| Street address |
Universitaetsstr. 1
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| City |
Duesseldorf |
| ZIP/Postal code |
40225 |
| Country |
Germany |
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| Platforms (2) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
| GPL17062 |
Agilent-024416 human_miRNA_v13 [miRBase release 13.0 miRNA ID version] |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA196140 |
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