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miR-290 acts as a physiological effector of senescence in mouse embryo fibroblasts.

Abstract
The culture-induced senescence of mouse embryo fibroblasts (MEF) correlates with reduction of cell proliferation. In this work we found that the accumulation of cells with 4C DNA content and the transcriptional change of several microRNAs (miRNAs or miRs) are relevant events in culture senescence. By comparing the miRNA expression profiles of physiologically senescent MEF and that of senescent MEF induced by the downregulation of leukemia-related factor, we identified miR-290 as a common upregulated miRNA. When miR-290 was transfected in presenescent MEF, SA-beta-gal(+) cells and p16, two markers of culture senescence, increased compared with control, indicating that miR-290 is causally involved in senescence. Interestingly, nocodazole (NCZ), which induces G2/M block, increased the percentage of senescent cells as well as the expression of miR-290 and of the tumor suppressor p16, thus mimicking culture senescence. As miR-290 was overexpressed in NCZ-treated cells and it was able to induce senescence in proliferating MEF, we investigated whether miR-290 and NCZ could share common mechanisms of culture senescence. Whereas the induction of SA-beta-gal(+) by miR-290 was not strengthened by coupling its transfection with NCZ treatment, the transfection of the antagomir 290 (d-290) plus NCZ treatment, while blocking cells at G2/M, suppressed SA-beta-gal(+) and p16 induction. On the basis of these findings we conclude that miR-290 might act as a physiological effector of NCZ induced as well as culture senescence via p16 regulation expanding the role of this miRNA from embryonic stem to differentiated cells.
AuthorsLetizia Pitto, Milena Rizzo, Marcella Simili, Daria Colligiani, Monica Evangelista, Alberto Mercatanti, Laura Mariani, Federico Cremisi, Giuseppe Rainaldi
JournalPhysiological genomics (Physiol Genomics) Vol. 39 Issue 3 Pg. 210-8 (Nov 06 2009) ISSN: 1531-2267 [Electronic] United States
PMID19723773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • MIRN290 microRNA, mouse
  • MicroRNAs
  • Nocodazole
Topics
  • Animals
  • Cells, Cultured
  • Cellular Senescence (drug effects, genetics)
  • Cyclin-Dependent Kinase Inhibitor p16 (genetics)
  • Cyclin-Dependent Kinase Inhibitor p21 (genetics)
  • Embryo, Mammalian (cytology)
  • Fibroblasts (cytology, metabolism)
  • Gene Expression Profiling
  • Gene Expression Regulation (drug effects)
  • Mice
  • MicroRNAs (genetics)
  • Nocodazole (pharmacology)
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction

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