MicroRNAs involved in kidney disease and injury

Micro ribonucleic acids (miRNAs) are short, non-coding RNA molecules that regulate gene expression typically by repressing translation. These miRNAs bind to their respective messenger RNA (mRNA) targets and initiate the RNA-induced silencing complex (RISC), which degrades the mRNA or it’s translated protein product. MiRNAs are a form of epigenetic regulation involved in basic cell functions and disease programming. MiRNAs are influenced by environmental exposures, which may contribute to adverse health effects. The aims of this study were to identify miRNAs involved in kidney disease in injury that may be mediated by environmental metal exposures, and assess the functional role of these miRNAs in the cell. First, metal-altered miRNAs related to kidney damage in humans were reviewed in the literature. The toxic metals of interest included arsenic, cadmium, and lead. We identified miR-21 and miR-221 as miRNAs altered by exposure to heavy metals (arsenic and lead). Next, miRNA levels that were significantly up-regulated or down-regulated in patients with kidney disease from previous literature were identified. A list of 52 miRNAs was collated from four reviews, all of which measured miRNA expression in human urine. Of note, miR-21 was common to the metal-altered and kidney disease-associated lists. Lastly, Ingenuity Pathway Analysis, a program to interpret genomics data, was applied to analyze kidney disease-associated miRNA pathways and predict downstream gene targets. The most significant network of kidney disease-associated miRNAs was enriched for cancer, organismal injury and abnormalities, and reproductive system disease (p<1x10^-32). The second most significant network was enriched for cancer, endocrine system disorders, and gastrointestinal disease (p<1x10^-31). This research informs us of miRNAs associated with kidney disease that may serve as biomarkers or future targets for intervention. In addition, miR-21 represents a putative marker of potentially preventable environmentally-mediated disease that will be prioritized in future studies.