Elevated miR-34c-5p mediates dermal fibroblast senescence by ultraviolet irradiation

Int J Biol Sci. 2013 Aug 9;9(7):743-52. doi: 10.7150/ijbs.5345. eCollection 2013.

Abstract

Previous studies showed that several miRNAs can regulate pathways involved in UVB-induced premature senescence and response to ultraviolet irradiation. It has also been reported that miR-34c-5p may be involved in senescence-related mechanisms. We propose that miR-34c-5p may play a crucial role in senescence of normal human primary dermal fibroblasts. Here, we explored the roles of miR-34c-5p in UVB-induced premature senescence on dermal fibroblasts. MiR-34c-5p expression was increased in dermal fibroblasts after repeated subcytotoxic UVB treatments. Underexpression of miR-34c-5p in dermal fibroblasts led to a marked delay of many senescent phenotypes induced by repeated UVB treatments. Furthermore, underexpression of miR-34c-5p in dermal fibroblasts can antagonize the alteration of G1-arrested fibroblasts. Moreover, E2F3, which can inactivate p53 pathway and play a role in cell cycle progression, is a down-stream target of miR-34c-5p. Forced down-expression of miR-34c-5p decreased the expression of UVB-SIPS induced P21 and P53 at both mRNA and protein levels. Our data demonstrated that down-regulation of miR-34c-5p can protect human primary dermal fibroblasts from UVB-induced premature senescence via regulations of some senescence-related molecules.

Keywords: UVB; human skin fibroblasts.; miR-34c-5p; premature senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cellular Senescence / genetics
  • Cellular Senescence / radiation effects*
  • Child
  • Down-Regulation
  • E2F3 Transcription Factor / biosynthesis
  • Fibroblasts / cytology
  • Fibroblasts / radiation effects*
  • Humans
  • Male
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Skin / cytology
  • Skin / radiation effects
  • Tumor Suppressor Protein p53 / biosynthesis
  • Ultraviolet Rays*
  • p21-Activated Kinases / biosynthesis

Substances

  • E2F3 Transcription Factor
  • E2F3 protein, human
  • MIRN34 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • p21-Activated Kinases