The liver is considered the major target organ affected by oral exposure to titanium dioxide nanoparticles (TiO2 NPs), but the mechanism of hepatotoxicity is not fully understood. This study investigated the effect of TiO2 NPs on the expression profile of long non-coding RNA (lncRNA) in hepatocytes and tried to understand the potential mechanism of hepatotoxicity through bioinformatics analysis. The human hepatocellular carcinoma cells (HepG2) were treated with TiO2 NPs at doses of 0-200 μg/mL for 48 h and then RNA sequencing was implemented. The differential lncRNAs between the control and TiO2 NPs-treated groups were screened, then the lncRNA-mRNA network and enrichment pathways were analyzed via multivariate statistics. As a result, 46,759 lncRNAs were identified and 129 differential lncRNAs were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the targeted mRNAs of those differential lncRNAs were enriched in the Hedgehog signaling pathway, Vasopressin-regulated water reabsorption, and Glutamatergic synapse. Moreover, two lncRNA-mRNA networks, including lncRNA NONHSAT256380.1-JRK and lncRNA NONHSAT173563.1-SMIM22, were verified by mRNA detection. This study demonstrated that an alteration in the lncRNA expression profile could be induced by TiO2 NPs and epigenetics may play an important role in the mechanism of hepatotoxicity.
Keywords: RNA sequencing; epigenetics; hepatotoxicity; lncRNAs; titanium dioxide nanoparticles.