Genome-wide transcriptional profiling and functional analysis reveal miR-330-MAPK15 axis involving in cellular responses to deoxynivalenol exposure

Abstract

Deoxynivalenol (DON) is one of the mycotoxins that is toxic to agricultural environment, which poses high risks to human and farm animal health. Noncoding RNAs have been shown to be crucial regulators of toxicological processes and as promising biomarkers for toxicity monitoring and prevention of mycotoxin contamination. Herein, we characterized genome-wide transcriptional profiling of porcine intestinal epithelial cells upon DON exposure and illustrated a subset of miRNAs and lncRNAs involved in the cellular processes by targeting genes associated with stress responses. A total of 110 differential expression miRNAs and 143 differential expression lncRNAs were identified between the DON exposure and control cell samples. Interactive network analysis showed that miR-330 was one hub noncoding RNA, expression of which was significantly increased upon DON exposure. Functional enrichment analysis indicated that the genes involved in the networks were mainly enriched in the terms of plasma membrane bounded cell projection assembly, mRNA processing, and regulation of mitochondrion organization. Further functional analysis revealed that high expression of miR-330 inhibits the reactive oxygen species production, cell apoptosis, and autophagic flux in cells upon DON exposure. Luciferase assay further indicated that miR-330 could directly target MAPK15. Knockdown of MAPK15 resulted in decreased reactive oxygen species level and cell apoptosis induced by DON, indicating the existence of miR-330-MAPK15 regulatory axis in regulating DON toxicity. Our work shed novel insights into the mode of action of DON at cellular level and indicated the potential of miR-330 as a biomarker for toxicity monitoring of DON contamination, which contributes to the development of effective biomonitoring and prevention strategies to reduce the toxicological effects of DON.