MicroRNA Response and Toxicity of Potential Pathways in Human Colon Cancer Cells Exposed to Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO-NPs) are widely used for biomedical and food applications, the toxicity of TiO-NPs in vivo and in vitro has been elucidated, but the underlying cytotoxicity of TiO-NPs against microRNA remains largely unknown. The purpose of this study was to analyze microRNA profiling induced by TiO-NPs against NCM460 and HCT116 cell lines. Comparative analysis identified 34 and 24 microRNAs were significantly altered in the TiO-NPs treated cells at concentrations of 3 and 30 μg/mL, respectively. Functional classification demonstrated that a large proportion of genes involved in metabolism, human disease, and environmental information process were significantly upregulated by TiO-NPs. Bioinformatics analysis suggested that microRNA 378 might be an early indicator of cellular response to exogenous stimuli with apoptotic signals. Furthermore, TiO-NPs significantly altered the expression of microRNA 378b and 378g in HCT116 and NCM460 cell lines at different concentrations from 3 to 6 μg/mL. These concentrations elicit high-sensitivity of stimuli response in colon cancer cells when exposed to the slight doses of TiO-NPs. Our study indicated that microRNAs 378b and 378g may play an important role in TiO-NPs-mediated colonic cytotoxicity, which may provide a valuable insight into the molecular mechanisms of potential risks in colitis and colon cancer.