Amorphous silica nanoparticles induce tumorigenesis via regulating ATP5H/SOD1-related oxidative stress, oxidative phosphorylation and EIF4G2/PABPC1-associated translational initiation

• Published in: PeerJ (San Francisco, CA) Vol. 7; p. e6455
• Main Authors: Xie, Dongli, Zhou, Yang, Luo, Xiaogang
• Format: Journal Article
• Language: English
• Published: United States PeerJ. Ltd 04.03.2019; PeerJ, Inc; PeerJ Inc
• Subjects: Amorphous silica nanoparticles; B cells; Biochemistry; Bioinformatics; Cancer; DNA microarrays; Ecotoxicology; Environmental Impacts; Epithelial cells; Gene expression; Genes; Genetic transformation; Initiation factor eIF-4G; Laboratories; Medical research; MicroRNA; MicroRNAs; Nanoparticles; Nanotechnology; Oxidative phosphorylation; Oxidative stress; Phosphorylation; Protein arrays; Protein binding; Protein-protein interactions; Proteins; Reactive oxygen species; Silica; Silicon dioxide; Software; Superoxide dismutase; Superoxides; Toxicity; Toxicology; Translation (Genetics); Translational initiation; Tumorigenesis; Tumors; China; Oxidative stress; Translational initiation; Tumorigenesis; Oxidative phosphorylation; Amorphous silica nanoparticles; MicroRNAs
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.6455

Recent studies indicate amorphous silica nanoparticles (SiNPs), one of the widely applied nanomaterials, have potential toxicity in humans and induces cell malignant transformation. However, its carcinogenic mechanisms remain poorly understood. This study's purpose was to investigate the underlying toxic mechanisms of amorphous SiNPs on human lung epithelial cells model by using microarray data. Microarray dataset GSE82062 was collected from Gene Expression Omnibus database, including three repeats of Beas-2B exposed to amorphous SiNPs for 40 passages and three repeats of passage-matched control Beas-2B cells. Differentially expressed genes (DEGs) were identified using linear models for microarray data method. Protein-protein interaction (PPI) network was constructed using data from the STRING database followed by module analysis. The miRwalk2 database was used to predict the underlying target genes of differentially miRNAs. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. A total of 323 genes were identified as DEGs, including 280 downregulated (containing 12 pre-miRNAs) and 43 upregulated genes (containing 29 pre-miRNAs). Function enrichment indicated these genes were involved in translational initiation (i.e., eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), poly (A) binding protein cytoplasmic 1 (PABPC1)), response to reactive oxygen species (i.e., superoxide dismutase 1 (SOD1)) and oxidative phosphorylation (i.e., ATP5H). PABPC1 (degree = 15), ATP5H (degree = 11) and SOD1 (degree = 8)] were proved to be hub genes after PPI-module analyses. ATP5H/SOD1 and EIF4G2/PABPC1 were overlapped with the target genes of differentially expressed pre-miR-3648/572/661 and pre-miR-4521. Amorphous SiNPs may induce tumorigenesis via influencing ATP5H/SOD1-related oxidative stress, oxidative phosphorylation and EIF4G2/PABPC1-associated translational initiation which may be regulated by miR-3648/572/661 and miR-4521, respectively.