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

Abstract

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–Cu²⁺) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB–Cu²⁺-induced changes in the miRNA profile of renal cells and examine which biological processes are significantly affected by AmB–Cu²⁺. 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–Cu²⁺ 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–Cu²⁺- and AmB-treated cells. AmB–Cu²⁺ influenced both the miRNA and mRNA profiles much more strongly than AmB. The most affected biological processes were intracellular signal transduction (AmB–Cu²⁺) 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.

Keywords:

• Amphotericin B
• copper complexes
• oligonucleotide microarrays
• miRNA arrays
• renal cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by National Science Centre of Poland on the basis of decision no. DEC-2012/05/B/NZ1/00037 and KNW-1-029/N/6/0.