Bioinformatic Analysis for Exploring Target Genes and Molecular Mechanisms of Cadmium-Induced Nonalcoholic Fatty Liver Disease and Targeted Drug Prediction.

Abstract

Cadmium (Cd) is a widely available metal that has been found to have a role in causing nonalcoholic fatty liver disease (NAFLD). However, the detailed toxicological targets and mechanisms by which Cd causes NAFLD are unknown. Therefore, the present work aims to reveal the main targets of action, cellular processes, and molecular pathways by which cadmium causes NAFLD. As shown in the bioinformatics analysis, there were 74 main targets of action for cadmium-induced NAFLD, hemopoietic cell kinase (HCK), EPH receptor A2 (EPHA2), MYC proto-oncogene (MYC), lysyl oxidase (LOX), dipeptidyl peptidase 7 (DPP7), nuclear factor erythroid 2-related factor 2 (NFE2L2), dual specificity phosphatase 6 (DUSP6), CD2 cytoplasmic tail binding protein 2 (CD2BP2), notch receptor 3 (NOTCH3), and phospholipase A2 group IVA (PLA2G4A) were screened as core genes. Testing these core genes in other databases, three differentially expressed genes, HCK, MYC, and DUSP6 were verified and used as targets for drug prediction in DsigDB; decitabine and retinoic acid were screened as potential therapeutic drugs for NAFLD based on the p-value and the combined score. The results of molecular docking showed that the predicted drugs can bind well to the core targets. In conclusion, cadmium is associated with NAFLD; the identified cadmium-toxicity targets, HCK, MYC, and DUSP6, may serve as biomarkers for the diagnosis of NAFLD and predicted drugs, decitabine and retinoic acid may have a potential role in the treatment of NAFLD.