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

Oxidative Medicine and Cellular Longevity
Lavinia TinaburriElena Dellambra

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...Continue Reading

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Citations

Jan 16, 2019·Cellular Oncology (Dordrecht)·Safieh Ebrahimi, Seyed Isaac Hashemy
Nov 30, 2019·International Journal of Molecular Sciences·Luca FaniaElena Dellambra
Mar 14, 2020·Journal of Applied Toxicology : JAT·Thelma Pavesi, Josino Costa Moreira
Sep 27, 2019·Journal of Psychopharmacology·Mahnaz AhmadimaneshLeila Etemad
Sep 16, 2020·The Journal of Investigative Dermatology·Lavinia TinaburriElena Dellambra

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Methods Mentioned

BETA
biopsies
biopsy
dissecting
PCR
Antibody Array
flow cytometry

Software Mentioned

miRanda
Quantity One
TargetScan

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