Exposure to a Titanium Dioxide Product Alters MicroRNA Expression in Human Cells

The safety of titanium dioxide (TiO2), widely used in foods and personal care products, has been of on-going concern. Adverse effects of TiO2 have been reported, suggesting risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO2 product, to which humans could be exposed, on microRNA (miRNA) expression (a primary epigenetic mechanism) was investigated using human cell lines (Caco-2, HCT116 (colorectal) and HepG2, SNU387 (liver)) relevant to human exposure. The effect of TiO2 nanomaterial exposure on expression levels of miRNA was determined using the TaqMan Array Human microRNA A+B Card Set v3.0 platform. Differentially expressed miRNAs were identified (SNU387 (n = 112), HepG2 (n = 97), Caco-2 (n = 94), and HCT116 (n = 53)). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis of target genes provided insights into the roles of modulating pathways, which can be associated with diseases. Top 10 KEGG pathways in each cell line included MAPK signaling pathway, Axon guidance, cell cycle, Hippo signaling pathway, and Endocytosis. Findings from the study clearly demonstrate the impact of TiO2 exposure on miRNA expression, supporting the potential involvement of this epigenetic mechanism in its biological responses. Hence, epigenetic studies are important for the complete assessment of the potential risk from exposure.