MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers

Int J Mol Sci. 2021 Nov 7;22(21):12043. doi: 10.3390/ijms222112043.

Abstract

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.

Keywords: biomarker; deoxynivalenol; microRNA; mycotoxin; next generation sequencing.

MeSH terms

  • Animal Feed / adverse effects
  • Animals
  • Biomarkers, Pharmacological / analysis*
  • Biomarkers, Pharmacological / metabolism
  • Circulating MicroRNA / analysis
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics
  • Dietary Exposure / adverse effects
  • Dietary Exposure / analysis*
  • Female
  • Food Contamination / analysis
  • Gene Expression Profiling
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • MicroRNAs / analysis*
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • Mycotoxins / pharmacology
  • Swine
  • Toxicity Tests / veterinary
  • Trichothecenes / pharmacology*

Substances

  • Biomarkers, Pharmacological
  • Circulating MicroRNA
  • MicroRNAs
  • Mycotoxins
  • Trichothecenes
  • deoxynivalenol