a Department of Molecular Biology , School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia , Sosnowiec , Poland.
b Department of Cell Biology , Institute of Biology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland.
Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
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) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu-induced changes in the miRNA profile of renal cells and examine which biological processes are significantly affected by AmB-Cu. 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 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- and AmB-treated cells. AmB-Cu influenced both the miRNA and mRNA profiles much more strongly than AmB. The most affected biological processes were intracellular signal transduction (AmB-Cu) 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.
微小 RNA（miRNAs）已被报道调节重要的生物学过程，其表达受病理过程和药物诱导的毒性的影响。两性霉素 B（AmB）可引起肝和肾损伤，但最近开发的 AmB 与铜（II）离子的复合物（AmB-Cu）对人肾细胞的毒性较低，同时保持较高的抗真菌活性。我们的研究目的是评估 AmB-Cu 诱导的肾细胞 miRNA 谱变化，并检查哪些生物学过程受到 AmB-Cu 的显著影响。我们还旨在预测差异表达的 miRNAs 是否会影响观察到的 mRNA 谱变化。使用微阵列技术对用 AmB-Cu 或 AmB 处理的正常人肾近端小管上皮细胞（RPTEC）进行 miRNA 和 mRNA 谱分析。对于差异表达的 mRNAs，进行了 PANTHER 过表达二项式检验。使用 miRTar 工具预测 miRNA 靶标相互作用（MTIs）。AmB-Cu 和 AmB 处理的细胞中，mRNA 谱的变化比 miRNA 谱的变化更强烈。AmB-Cu 对 miRNA 和 mRNA 谱的影响都比 AmB 强得多。受影响最严重的生物学过程是细胞内信号转导（AmB-Cu）和信号转导（AmB）。发现分化的 miRNAs 和 mRNAs 之间的相互作用很少。参与信号转导和细胞内信号转导的基因的表达谱变化可能不是由于与差异表达的 miRNAs 相互作用而导致的。miRNA 谱的变化表明，受测试药物可能通过 miRNA 依赖的机制影响纤维化的调节。
