MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation

A. M. Lena, M. Mancini, P. Rivetti di Val Cervo, G. Saintigny, C. Mahé, G. Melino, E. Candi

Research output: Contribution to journalArticlepeer-review

Abstract

Keratinocyte replicative senescence has an important role in time-dependent changes of the epidermis, a tissue with high turnover. Senescence encompasses growth arrest during which cells remain metabolically active but acquire a typical enlarged, vacuolar and flattened morphology. It is also accompanied by the expression of endogenous senescence-associated-β-galactosidase and specific gene expression profiles. MicroRNAs levels have been shown to be modulated during keratinocytes senescence, playing key roles in inhibiting proliferation and in the acquisition of senescent markers. Here, we identify miR-191 as an anti-proliferative and replicative senescence-associated miRNA in primary human keratinocytes. Its overexpression is sufficient per se to induce senescence, as evaluated by induction of several senescence-associated markers. We show that SATB1 and CDK6 3'UTRs are two miR-191 direct targets involved in this pathway. Cdk6 and Satb1 protein levels decrease during keratinocytes replicative senescence and their silencing by siRNA is able to induce a G1 block in cell cycle, accompanied by an increase in senescence-associated markers.

Original languageEnglish
Pages (from-to)509-514
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume423
Issue number3
DOIs
Publication statusPublished - Jul 6 2012

Keywords

  • CDK6
  • Keratinocytes
  • MicroRNA-191
  • Proliferation
  • SATB1
  • Senescence

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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