PUBLICATION
Integration analysis of miRNA-mRNA uncovers the mechanisms of ochratoxin A-induced hepatotoxicity
- Authors
- Luo, Z., Jin, R., Pan, F., Guo, R., Li, M., Zhang, S., Shi, J., Zheng, J., Wang, H., Yang, X., Yang, J., Yu, G.
- ID
- ZDB-PUB-250315-15
- Date
- 2025
- Source
- Ecotoxicology and environmental safety 293: 118039118039 (Journal)
- Registered Authors
- Yang, Jian
- Keywords
- Hepatotoxicity, MRNA-seq, MiRNA-seq, Ochratoxin A
- MeSH Terms
-
- Animals
- Humans
- MicroRNAs*/genetics
- Reactive Oxygen Species/metabolism
- Cell Survival/drug effects
- RNA, Messenger*/genetics
- RNA, Messenger*/metabolism
- Liver/drug effects
- Zebrafish*
- Ochratoxins*/toxicity
- Chemical and Drug Induced Liver Injury/genetics
- Cell Line
- Apoptosis*/drug effects
- Cell Proliferation/drug effects
- PubMed
- 40086031 Full text @ Ecotoxicol. Environ. Saf.
Citation
Luo, Z., Jin, R., Pan, F., Guo, R., Li, M., Zhang, S., Shi, J., Zheng, J., Wang, H., Yang, X., Yang, J., Yu, G. (2025) Integration analysis of miRNA-mRNA uncovers the mechanisms of ochratoxin A-induced hepatotoxicity. Ecotoxicology and environmental safety. 293:118039118039.
Abstract
Ochratoxin A (OTA), the most toxic member of the ochratoxin family, is frequently detected in contaminated food and beverages, posing substantial health risks to both humans and animals, particularly due to its hepatotoxic effects. Although OTA is known to cause liver damage, the precise molecular mechanisms driving its toxicity remain poorly understood. In this study, we explored the hepatotoxic effects of OTA using LO2 cells and zebrafish models, combining miRNA and mRNA analyses to uncover the underlying mechanisms. Our results demonstrated that OTA significantly suppressed cell proliferation and viability, induced cell cycle arrest, triggered apoptosis and elevated reactive oxygen species (ROS) production in LO2 cells, with analogous apoptotic effects observed in zebrafish larvae. Additionally, miRNA-mRNA analysis revealed that differentially expressed genes (DEGs) and miRNAs (DEMs) were significantly enriched in pathways related to apoptosis, cell cycle regulation, and MAPK signaling. We constructed a potential regulatory network, identifying three key miRNAs (hsa-miR-3065-5p, hsa-miR-520g-3p, and hsa-miR-5698) and three associated hub mRNAs (CACNA1D, CDC6, and E2F1). Moreover, OTA treatment specifically induced p38 phosphorylation without significantly altering the phosphorylation levels of ERK or JNK. Collectively, this study established a comprehensive framework for understanding the hepatotoxic mechanisms of OTA at the miRNA and mRNA levels, providing critical insights into the pathogenesis of hepatotoxicity induced by ochratoxins and contributing to the prevention and management of related diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping