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

Abstract

Titanium dioxide nanoparticles (TiO2-NPs) are widely used for biomedical and food applications, the toxicity of TiO2-NPs in vivo and in vitro has been elucidated, but the underlying cytotoxicity of TiO2-NPs against microRNA remains largely unknown. The purpose of this study was to analyze microRNA profiling induced by TiO2-NPs against NCM460 and HCT116 cell lines. Comparative analysis identified 34 and 24 microRNAs were significantly altered in the TiO2-NPs treated cells at concentrations of 3 μg/mL 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 TiO2-NPs. Bioinformatics analysis suggested that microRNA 378 might be an early indicator of cellular response to exogenous stimuli with apoptotic signals. Furthermore, TiO2-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 TiO2-NPs. Our study indicated that microRNAs 378b and 378g may play an important role in TiO2-NPs-mediated colonic cytotoxicity, which may provide a valuable insight into the molecular mechanisms of potential risks in colitis and colon cancer.

Profiling Non-Coding RNA Changes Associated with 16 Different Engineered Nanomaterials in a Mouse Airway Exposure Model

“…Therefore, their use as a food additive has been banned since the beginning of 2020 in France (USDA Foreign Agricultural Service, GAIN Report Number: FR1917). A recent study suggests that cellular uptake of TiO2 ENM induces dose-dependent oxidative stress and alterations in microRNA expression [ 29 ]. Our results support the idea that TiO2p ENM are not toxicologically inert and do induce changes in epigenetic regulation, via shared as well as unique mechanisms when compared to the other tested ENM.…”

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

“…Table 3 shows an overview of recent publications summarizing the effects of TiO 2 nanoparticles and E171 on various cell models along the oro-gastrointestinal route, as well as cell types found in organs, following the systemic distribution of these particles. Some studies on TiO 2 showed the ability to decrease cell viability and induce the formation of ROS, while others do not detect such effects [ 16 , 57 , 58 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ]. In some cases, the increase in ROS was accompanied by elevated oxidative stress levels and lipid peroxidation, which may lead to the induction of DNA damage and micronuclei [ 16 , 123 , 127 , 129 , 130 ].…”

Analysis of the Characteristics and Cytotoxicity of Titanium Dioxide Nanomaterials Following Simulated In Vitro Digestion

“…A mechanism of reactive oxygen species (ROS) induction has been frequently related to nanotoxicity [44]. In fact, a recent work showed an intracellular increase of reactive oxygen species (ROS) upon exposure of normal human colon cell lines (NCM460) and human colon cancer cells (HCT116) to TiO 2 , that was suggested as the cause of its cytotoxicity and was related to microRNAs 378b and 378 g expression [45]. Increased uptake of smaller TiO 2 might favor this type of mechanisms, explaining the results observed in HT29-MTX-E12 cells exposed to digested NM-105, and deserves further research.…”