MicroRNA target-based network predicts androgen receptor-linked mycotoxin stress

Yuseok Moon; Tamás Korcsmáros; Arulkumar Nagappan; Navin Ray

doi:10.1016/j.ecoenv.2021.113130

MicroRNA target-based network predicts androgen receptor-linked mycotoxin stress

Ecotoxicol Environ Saf. 2022 Jan 15:230:113130. doi: 10.1016/j.ecoenv.2021.113130. Epub 2021 Dec 27.

Authors

Yuseok Moon¹, Tamás Korcsmáros², Arulkumar Nagappan³, Navin Ray³

Affiliations

¹ Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences and Biomedical Research Institute, Pusan National University, Yangsan 50612, Republic of Korea; Graduate Program of Genomic Data Sciences, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: moon@pnu.edu.
² Earlham Institute, Norwich NR4 7UZ, UK; Quadram Institute Bioscience, Norwich NR4 7UZ, UK.
³ Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences and Biomedical Research Institute, Pusan National University, Yangsan 50612, Republic of Korea.

PMID: 34968797
DOI: 10.1016/j.ecoenv.2021.113130

Abstract

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.

Keywords: Androgen receptor; Carcinogenesis; Mycotoxins.