OpenTox Virtual Conference 2022
MiRNA Target-based Network Prediction of Androgen Receptor-responsive Adverse Outcome of Mycotoxin Stress
1. Department of Integrative Biomedical Sciences, Pusan National University, Yangsan, Korea
2. Graduate Program of Genomic Data Sciences, Pusan National University, Yangsan, Korea * E-mail to the corresponding author: firstname.lastname@example.org
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 using network modeling integration. 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 according to clinical transcriptome datasets. 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 (This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF 2021R1I1A1A01056963).