Epigenetic versus Genetic Deregulation of the KEAP1/NRF2 Axis in Solid Tumors: Focus on Methylation and Noncoding RNAs

Figure 3

Left and right panels show how miRNA modifications may contribute to down and upregulate the KEAP1/NRF2 signaling in cancer. Representative scheme on the left side summarizes a group of miRNAs that directly target KEAP1 mRNA and indirectly impact on the transcriptional activity of the NRF2 into the nucleus. Other miRNAs modulate BACH1, a transcription factor that competes with NRF2 leading to the link at the antioxidant response element (ARE) of detoxifying genes. The schematic model on the right side depicts those miRNAs that directly target NFE2L2 and impact on the general mRNA and protein levels of NRF2 and, by consequence, on the activation of detoxification NRF2 target genes with a great impact on chemo- and radioresistance, survival, growth, and proliferation of tumor cells.