Protein and miRNA profiling of radiation-induced skin injury in rats: the protective role of peroxiredoxin-6 against ionizing radiation

Free Radic Biol Med. 2014 Apr;69:96-107. doi: 10.1016/j.freeradbiomed.2014.01.019. Epub 2014 Jan 19.

Abstract

Radiation-induced skin injury is a serious concern during radiotherapy. However, the molecular mechanism underlying the pathogenesis of radiation-induced skin injury has not been extensively reported. Most biological functions are performed and regulated by proteins and noncoding RNAs, including microRNAs (miRNAs). The interplay between mRNA and miRNA has been implicated in disease initiation and progression. Technical advances in genomics and proteomics have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathogenesis of radiation-induced skin injury. In this study, we compared the protein and miRNA expression in rat skin irradiated with a 45-Gy electron beam with expression from adjacent normal tissues. We found 24 preferentially expressed proteins and 12 dysregulated miRNAs in irradiated skin. By analyzing the protein and miRNA profiles using bioinformatics tools, we identified a possible interaction between miR-214 and peroxiredoxin-6 (PRDX-6). Next, we investigated the expression of PRDX-6 and the consequences of its dysregulation. PRDX-6 is suppressed by radiation-inducible miR-214 and is involved in the pathogenesis of radiation-induced skin injury. Overexpression of PRDX-6 conferred radioresistance on cells, decreased cell apoptosis, and preserved mitochondrial integrity after radiation exposure. In addition, in vivo transfection with PRDX-6 reduced radiation-induced reactive oxygen species and the malondialdehyde concentration and ameliorated radiation-induced skin damage in rats. Our present findings illustrate the molecular changes during radiation-induced skin injury and the important role of PRDX-6 in ameliorating this damage in rats.

Keywords: Free radicals; Peroxiredoxin-6; Protein and miRNA profiling; Radiation-induced skin injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / radiation effects
  • MicroRNAs / biosynthesis*
  • Peroxiredoxin VI / biosynthesis*
  • Peroxiredoxin VI / genetics
  • Protein Biosynthesis / radiation effects*
  • Radiation Tolerance / genetics
  • Radiation, Ionizing
  • Rats
  • Skin / injuries
  • Skin / metabolism*
  • Skin / pathology
  • Skin / radiation effects
  • Transcriptome

Substances

  • MicroRNAs
  • Peroxiredoxin VI
  • Prdx6 protein, rat