Stress-responsive
microRNAs (
miRNAs) contribute to the regulation of cellular homeostasis or
pathological processes, including
carcinogenesis, by reprogramming target gene expression following human exposure to environmental or dietary
xenobiotics. Herein, we predicted the targets of carcinogenic
mycotoxin-responsive
miRNAs and analyzed their association with disease and functionality.
miRNA target-derived prediction indicated potent associations of oncogenic
mycotoxin exposure with metabolism- or
hormone-related diseases, including
sex hormone-linked
cancers. Mechanistically, the signaling network evaluation suggested
androgen receptor (AR)-linked signaling as a common pivotal cluster associated with metabolism- or
hormone-related
tumorigenesis in response to
aflatoxin B1 and
ochratoxin A co-exposure. Particularly, high levels of AR and AR-linked genes for the
retinol and
xenobiotic metabolic
enzymes were positively associated with attenuated disease
biomarkers and good prognosis in patients with liver or
kidney cancers. Moreover, AR-linked signaling was protective against OTA-induced genetic insults in human hepatocytes whereas it was positively involved in AFB1-induced genotoxic actions. Collectively,
miRNA target network-based predictions provide novel clinical insights into the progression or intervention against malignant adverse outcomes of human exposure to environmental oncogenic insults.