Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer

As3+ will disrupt the tumor suppressor-like activity of AHR, either through preventing the formation of repressive complexes or the binding of the repressive complexes to these oncogenic genes. Meanwhile, the reduced AHR binding to the DNA may also enhance the nuclear translocation and transcriptional regulation of these oncogenic transcription factors, such as Nrf2 and HIF1α, leading to active transcription and expression of oncogenes and genes in the TGF and Nrf2 signaling pathways, which promotes carcinogenesis or tumorigenesis. Genome-wide ChIP-seq analysis of the global binding of AhR (Enzo) on the genome in the cells treated with As3+ (1 μM for 6 hrs) and RNA-seq analysis of differential expression between control cells and AHR KO cells.