MicroRNA target-based network predicts androgen receptor-linked mycotoxin stress
File(s)Mirna_ecotoxicology_Moon_2021.pdf (12.58 MB)
Published version
Author(s)
Moon, Yuseok
Korcsmaros, Tamas
Nagappan, Arulkumar
Ray, Navin
Type
Journal Article
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.
Date Issued
2022-01-15
Date Acceptance
2021-12-25
Citation
Ecotoxicology and Environmental Safety, 2022, 230
ISSN
0147-6513
Publisher
Elsevier
Journal / Book Title
Ecotoxicology and Environmental Safety
Volume
230
Copyright Statement
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000740094800005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Environmental Sciences
Toxicology
Environmental Sciences & Ecology
Mycotoxins
Androgen receptor
Carcinogenesis
HEPATOCELLULAR-CARCINOMA METASTASIS
TUMOR-SUPPRESSOR GENE
OXIDATIVE STRESS
OCHRATOXIN-A
RETINOL ESTERIFICATION
DIETARY OCHRATOXIN
ALL-TRANS
P53
ACID
CYTOCHROME-P450
Publication Status
Published
Article Number
ARTN 113130
Date Publish Online
2021-12-27