Integrated high-throughput small RNA and transcriptome sequencing unveil the shape-dependent toxicity of nano-alumina in rat astrocytes

Abstract Background The large-scale applications of alumina nanoparticles (Al 2 O 3 -NPs), one the most important NPs in global market, are causing severe damages to environment and human health. Our previous research has revealed a critical role nanoparticle morphology (e.g., flake rod) determining toxic potencies Al -NPs, where nanorods demonstrated significantly stronger response than that nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In present study, we evaluated compared potential toxicological two shapes γ-Al -NPs (flake versus by measuring miRNA mRNA profiles astrocytes rat cerebral cortex, ex vivo. Results A total 269 mRNAs 122 miRNAs, 180 116 miRNAs were differentially expressed after nanoflakes or exposure, respectively. Among them, 55 miR-760-5p, miR-326-3p, miR-35) 105 Kdm4d , Wdr62 Rps6 ) showed same trend between shapes. These mainly involved apoptosis, inflammatory pathways NF-kappa B), carcinogenic MAPK, p53, Notch, Rap1, Ras), cellular lipid metabolisms glycerolipid metabolism, sphingolipid, ether metabolism). remaining either an opposite only changed particular shape. Nanorods could specifically alter changes PI3K/Akt, AMPK TNF pathways, cell cycle, senescence, while caused Toll lmd signaling pathways. Conclusions Combined with results, further biomolecular leading toxicity nanoflakes, multi-omics is powerful approach elucidate morphology-related mode actions.