Kruppel-like factor 4 regulates keratinocyte senescence

Emanuele Panatta, Anna Maria Lena, Mara Mancini, Michela Affinati, Artem Smirnov, Margherita Annicchiarico-Petruzzelli, Maria Cristina Piro, Elena Campione, Luca Bianchi, Cinzia Mazzanti, Gerry Melino, Eleonora Candi

Research output: Contribution to journalArticle

Abstract

Keratinocyte replicative senescence has an important role in time-related changes of epidermis. Previous studies demonstrated that miRNAs play key roles in inhibiting proliferation and in the acquisition of the keratinocyte senescent phenotype as well as in individual ageing. Kruppel-like factor 4 is a transcription factor with dual functions in keratinocytes, being a stemness factor and a pro-differentiation factor. Interestingly, in skin squamous cell carcinomas KLF4 expression is strongly down-regulated or absent. While KLF4 involvement in senescence and ageing has not been investigated yet. Here, we show that Klf4 protein decreases during keratinocyte replicative senescence and during physiological skin aging, while its mRNA level does not change. We demonstrated that the senescence-associated miR-34a regulates post-transcriptionally Klf4 expression. KLF4 silencing is sufficient to induce a senescent phenotype in primary keratinocytes and ectopic miR-34a over-expression phenocopies this result. Our findings identify a novel regulatory loop between miR-34a and KLF4 during keratinocytes replicative senescence. This regulatory loop, beside aging, may play a role in age-related pathologies.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume499
Issue number2
DOIs
Publication statusPublished - May 5 2018

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Keywords

  • Epidermis
  • Keratinocytes
  • Klf4
  • miR-34a
  • Senescence
  • Skin aging

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Panatta, E., Lena, A. M., Mancini, M., Affinati, M., Smirnov, A., Annicchiarico-Petruzzelli, M., Piro, M. C., Campione, E., Bianchi, L., Mazzanti, C., Melino, G., & Candi, E. (2018). Kruppel-like factor 4 regulates keratinocyte senescence. Biochemical and Biophysical Research Communications, 499(2), 389-395. https://doi.org/10.1016/j.bbrc.2018.03.172