Evaluating the cytotoxicity and pathogenicity of multi-walled carbon nanotube through weighted gene co-expression network analysis: a nanotoxicogenomics study

Abstract

Background: Multi-walled carbon nanotube (MWCNT) is one of the most momentous carbonaceous nanoparticles which is widely used for various applications such as electronics, vehicles, and therapeutics. However, their possible toxicity and adverse effects convert them into a major health threat for humans and animals. Results: In this study, we employed weighted gene co-expression network analysis (WGCNA) to identify the co-expressed gene groups and dysregulated pathways due to the MWCNT exposure. For this purpose, three weighted gene co-expression networks for the microarray gene expression profiles of the mouse after 1, 6, and 12-month post-exposure to MWCNT were constructed. The module-trait analysis specified the significant modules related to different doses (1, 10, 40, and 80 µg) of MWCNT. Afterward, common genes between co-regulated and differentially expressed genes were determined. The further pathway analysis highlighted the enrichment of genes including Actb, Ube2b, Psme3, Ezh2, Alas2, S100a10, Ypel5, Rhoa, Rac1, Ube2l6, Prdx2, Ctsb, Bnip3l, Gp6, Myh9, Ube2k, Mbnl1, Kbtbd8, Riok3, Itgb1, Rap1a, and Atp5h in immune-, inflammation-, and protein metabolism-related pathways. Conclusions: This study discloses the genotoxicity and cytotoxicity effects of various doses of MWCNT which also affect the metabolism system. The identified genes can serve as potential biomarkers and therapeutic candidates. However, further studies should be performed to validate them in human cells.