Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions

• Published in: Toxicology mechanisms and methods Vol. 27; no. 7; pp. 537 - 543
• Main Authors: Gola, Joanna Magdalena, Strzałka-Mrozik, Barbara, Kruszniewska-Rajs, Celina, Adamska, Jolanta, Gagoś, Mariusz, Mazurek, Urszula
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.09.2017
• Subjects: Amphotericin B; Amphotericin B - adverse effects; Amphotericin B - pharmacology; Antifungal Agents - adverse effects; Antifungal Agents - pharmacology; Cell Communication - drug effects; Cells, Cultured; Coordination Complexes - adverse effects; Coordination Complexes - pharmacology; Copper - adverse effects; Copper - pharmacology; copper complexes; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humans; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; MicroRNAs - metabolism; miRNA arrays; oligonucleotide microarrays; renal cells; RNA, Messenger - metabolism; Signal Transduction - drug effects; Statistics as Topic; oligonucleotide microarrays; Amphotericin B; copper complexes; renal cells; miRNA arrays
• ISSN: 1537-6516; 1537-6524
• DOI: 10.1080/15376516.2017.1333554

MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu 2+ ) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu 2+ -induced changes in the miRNA profile of renal cells and examine which biological processes are significantly affected by AmB-Cu 2+ . We also aimed to predict whether differentially expressed miRNAs would influence observed changes in the mRNA profile. miRNA and mRNA profiles in normal human renal proximal tubule epithelial cells (RPTEC) treated with AmB-Cu 2+ or AmB were appointed with the use of microarray technology. For differentially expressed mRNAs, the PANTHER overrepresentation binomial test was performed. miRNA target interactions (MTIs) were predicted using the miRTar tool. The mRNA profile was much more strongly affected than the miRNA profile, in both AmB-Cu 2+ - and AmB-treated cells. AmB-Cu 2+ influenced both the miRNA and mRNA profiles much more strongly than AmB. The most affected biological processes were intracellular signal transduction (AmB-Cu 2+ ) and signal transduction (AmB). Only a few interactions between differentiating miRNAs and mRNAs were found. Changes in the profiles of genes involved in signal transduction and intracellular signal transduction may not result from interactions with differentially expressed miRNAs. Changes in the miRNA profile suggest the possible influence of tested drugs on the regulation of fibrosis via a miRNA-dependent mechanism.