MicroRNA–Gene Interactions Impacted by Toxic Metal(oid)s during EMT and Carcinogenesis

SIMPLE SUMMARY: Epithelial–mesenchymal transition is characterized by the loss of cellular adhesion and an increase in cellular motility. This phenomenon is mediated through several oncogenic signaling pathways. MicroRNAs are epigenetic regulators that can modulate both oncogenic signaling pathways and the expression of cellular adhesion proteins. Many toxic metal(loid)s are known human carcinogens and can modulate microRNA expression, resulting in epithelial–mesenchymal transition and carcinogenesis. This mini review summarizes the microRNA–gene interactions of toxic metal(loid)s in epithelial–mesenchymal transition and carcinogenesis. By doing so, we hope to highlight certain miRNAs that can be potential therapeutic targets in treating metal carcinogenesis. We also present original research findings that further characterize the mechanisms of cadmium-induced epithelial–mesenchymal transition. ABSTRACT: Chronic environmental exposure to toxic metal(loid)s significantly contributes to human cancer development and progression. It is estimated that approximately 90% of cancer deaths are a result of metastasis of malignant cells, which is initiated by epithelial–mesenchymal transition (EMT) during early carcinogenesis. EMT is regulated by many families of genes and microRNAs (miRNAs) that control signaling pathways for cell survival, death, and/or differentiation. Recent mechanistic studies have shown that toxic metal(loid)s alter the expression of miRNAs responsible for regulating the expression of genes involved in EMT. Altered miRNA expressions have the potential to be biomarkers for predicting survival and responses to treatment in cancers. Significantly, miRNAs can be developed as therapeutic targets for cancer patients in the clinic. In this mini review, we summarize key findings from recent studies that highlight chemical–miRNA–gene interactions leading to the perturbation of EMT after exposure to toxic metal(loid)s including arsenic, cadmium, nickel, and chromium.