miR-200a Modulates the Expression of the DNA Repair Protein OGG1 Playing a Role in Aging of Primary Human Keratinocytes

Lavinia Tinaburri, Mariarosaria D'Errico, Sara Sileno, Riccardo Maurelli, Paolo Degan, Alessandra Magenta, Elena Dellambra

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative DNA damage accumulation may induce cellular senescence. Notably, senescent cells accumulate in aged tissues and are present at the sites of age-related pathologies. Although the signaling of DNA strand breaks has been extensively studied, the role of oxidative base lesions has not fully investigated in primary human keratinocyte aging. In this study, we show that primary human keratinocytes from elderly donors are characterized by a significant accumulation of the oxidative base lesion 8-OH-dG, impairment of oxidative DNA repair, and increase of miR-200a levels. Notably, OGG1-2a, a critical enzyme for 8-OH-dG repair, is a direct target of miR-200a and its expression levels significantly decrease in aged keratinocytes. The 8-OH-dG accumulation displays a significant linear relationship with the aging biomarker p16 expression during keratinocyte senescence. Interestingly, we found that miR-200a overexpression down-modulates its putative target Bmi-1, a well-known p16 repressor, and up-regulates p16 itself. miR-200a overexpression also up-regulates the NLRP3 inflammasome and IL-1β expression. Of note, primary keratinocytes from elderly donors are characterized by NRPL3 activation and IL-1β secretion. These findings point to miR-200a as key player in primary human keratinocyte aging since it is able to reduce oxidative DNA repair activity and may induce several senescence features through p16 and IL-1β up-regulation.

Original languageEnglish
Pages (from-to)9147326
JournalOxidative Medicine and Cellular Longevity
Volume2018
DOIs
Publication statusPublished - Mar 25 2018

Keywords

  • 3T3 Cells
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cellular Senescence/physiology
  • Child
  • Child, Preschool
  • DNA Glycosylases/biosynthesis
  • DNA Repair
  • Humans
  • Keratinocytes/cytology
  • Mice
  • MicroRNAs/genetics
  • Middle Aged
  • Young Adult

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