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

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.

Exosomal miR‐374c‐5p derived from mesenchymal stem cells suppresses epithelial‐mesenchymal transition of hepatocellular carcinoma via the LIMK1‐Wnt/β‐catenin axis

“…EMT is characterized by the loss of epithelial phenotypes and gain of mesenchymal features, which endow cancer cells with higher metastatic ability and contribute to cancer cell dissemination 8 . Dysregulation of microRNAs (miRNAs) plays important role in the metastasis of various cancers 9,10 . Some cancer‐suppressing miRNAs are downregulated in HCC, which at least partially results in cancer metastasis 11,12 .…”