Silver, gold, and iron oxide nanoparticles alter miRNA expression but do not affect DNA methylation in HepG2 cells

Abstract

The increasing use of nanoparticles (NPs) in various applications entails the need for reliable assessment of their potential toxicity for humans. Originally, studies concerning the toxicity of NPs focused on cytotoxic and genotoxic effects, but more recently, attention has been paid to epigenetic changes induced by nanoparticles. In the present research, we analysed the DNA methylation status of genes related to inflammation and apoptosis as well as the expression of miRNAs related to these processes in response to silver (AgNPs), gold (AuNPs), and superparamagnetic iron oxide nanoparticles (SPIONs) at low cytotoxic doses in HepG2 cells. There were no significant differences between treated and control cells in the DNA methylation status. We identified nine miRNAs, the expression of which was significantly altered by treatment with nanoparticles. The highest number of changes was induced by AgNPs (six miRNAs), followed by AuNPs (four miRNAs) and SPIONs (two miRNAs). Among others, AgNPs suppressed miR-34a expression, which is of particular interest since it may be responsible for the previously observed AgNPs-mediated HepG2 cells sensitisation to tumour necrosis factor (TNF). Most of the miRNAs affected by NP treatment in the present study have been previously shown to inhibit cell proliferation and tumourigenesis. However, based on the observed changes in miRNA expression we cannot draw definite conclusions regarding the pro- or anti-tumour nature of the NPs under study. Further research is needed to fully elucidate the relation between observed changes in miRNA expression and the effect of NPs observed at the cellular level. The results of the present study support the idea of including epigenetic testing during the toxicological assessment of the biological interaction of nanomaterials.