Abstract:

Objective To identify the genes related to liver injury induced by hexavalent chromium ［Cr（Ⅵ）］ through the bioinformatics method， and to provide the new direction for further research on the mechanism of liver injury induced by Cr（Ⅵ）. Methods The data sets related to “［Cr （Ⅵ）］ liver” in the Gene Expression Omnibus （GEO） Database were searched， the data set GSE65198 was downloaded； the differentially expressed genes （DEGs） were screened through limma algorithm； Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed； STRING Database was used to analyze the protein-protein interaction （PPI） network； Cytohubba plug-in was used to screen the hub genes； the targeted drug molecules were predicted by Drug Characterization Database in Enrichr website. Results Twenty samples from the GSE65198 data set were selected and divided into two groups. In the first group， there were five liver samples 1 d after single exposure to 20 mg·kg^－1 Cr （Ⅵ） and five control samples； in the second group， there were five liver samples 7 d after single exposure to 20 mg.kg^－1 Cr （Ⅵ） and five control samples；the control samples in each group were regarded as the negative control，and 342 and 61 DEGs were screened （|log₂ FC|>1 and P<0.05）. The GO enrichment analysis results showed that the DEGs were mainly enriched in the biological processes such as the drug response， mitosis， senescence and so on； the KEGG analysis results showed that the main signaling pathways included the ribosome biogenesis， cell cycle regulation，and p53 signaling pathway and so on. The hub gene analysis results in the PPI network showed that the EBNA1 binding protein 2 （EBNA1BP2）， nucleolar protein 58 （NOP58）， guanine nucleotide binding protein like 3 （GNL3）， nucleolar protein 56 （NOP56）， and WD repeat domain 12 （WDR12） in 1 d group after single exposure and cyclin B2 （CCNB2） （the identifier in PPI network was ENSRNOP00000017117）， cyclin A2 （CCNA2） cyclin B1 （CCNB1）， cyclin dependent kinase 1 （CDK1）， and kinesin family member 20B （KIF20B） in 7 d group after single exposure were screened as the hub genes. The targeted drug prediction results showed that roscovetine and other drugs were identified as the targeted drugs for liver injury by induced Cr（Ⅵ）. Conclusion The mechanism of liver injury induced by Cr（Ⅵ） may be related to cell cycle regulation-related genes， and roscovitine may be the potential clinical treatment drug.

Key words: Hexavalent chromium, Liver, Bioinformatics, Differentially expressed genes, Injury