The Effects of a Mixture of Cadmium, Lead, and Mercury on Metabolic Syndrome and Its Components, as well as Cognitive Impairment: Genes, MicroRNAs, Transcription Factors, and Sponge Relationships

Converging evidence indicates heavy metal-induced genes, transcription factors (TFs), and microRNAs (miRNAs) are critical pathological components of metabolic syndrome (MetS) and cognitive impairment. Thus, our goals are to identify the interaction of mixed heavy metals (cadmium + lead + mercury) with genes, TFs, and miRNAs involved in MetS and its components, as well as cognitive impairment development. The most commonly retrieved genes for each disease were different, but essential biological pathways such as oxidative stress, altered lipoprotein metabolism, fluid shear stress and atherosclerosis, apoptosis, the IL-6 signaling pathway, and Alzheimer's disease were highlighted. The genes CASP3, BAX, BCL2, IL6, TNF, APOE, HMOX1, and IGF were found to be mutually affected by the heavy metal mixture studied, suggesting the importance of apoptosis, inflammation, lipid, heme, and glucose metabolism in MetS and cognitive impairment, as well as the potentiality of targeting these genes in prospective therapeutic intervention for these diseases. EGR2, ATF3, and NFE2L2 were noted as the most key TFs implicated in the etiology of MetS and its components, as well as cognitive impairment. We also found six miRNAs induced by studied heavy metals were the mutual miRNAs linked to MetS, its components, and cognitive impairment. In particular, we used miRNAsong to construct and verify a miRNA sponge sequence for these miRNAs. These sponges are promising molecules for the treatment of MetS and its components, as well as cognitive impairment.