Cooperative application of transcriptomics and ceRNA hypothesis: lncRNA-00742/miR-116 targets CD74 to mediate vanadium-induced mitochondrial apoptosis in duck liver

• Published in: Journal of hazardous materials 2024-12, Vol.480, p.135904, Article 135904
• Main Authors: Chen, Jing, Dai, Xueyan, Xing, Chenghong, Zhang, Yike, Cao, Huabin, Hu, Guoliang, Guo, Xiaoquan, Gao, Xiaona, Liu, Ping, Yang, Fan
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - metabolism; Apoptosis - drug effects; Duck; Ducks - genetics; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatotoxicity; Histocompatibility Antigens Class II; Liver - drug effects; Liver - metabolism; Liver - pathology; LncRNA-00742/miR-116/CD74; MicroRNAs - genetics; MicroRNAs - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial apoptosis; RNA, Competitive Endogenous; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Transcriptome - drug effects; Vanadium; Vanadium - toxicity
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.135904

Vanadium (V) is a poisonous metallic environmental pollutant which poses hazard to the animal health of the liver. Competitive endogenous ribonucleic acids (ceRNAs) are essential elements of mitochondrial function and apoptosis, and their effects have been associated with the metal toxicity mechanism. However, the specific mechanism of ceRNAs in V-induced mitochondrial apoptosis in the liver has not been adequately investigated. Hence, we established an in vivo model of ducks exposed to V for 44 days and an in vitro model of V exposure duck hepatocyte knockdown/overexpression. Results showed that V exposure triggered the differential expression of 1106 lncRNAs and 11 miRNAs in the liver. Besides, we established the lncRNA-00742/miR-116/CD74 regulatory network by the dual luciferase reporter gene. Our results also found that V induced mitochondrial injury and up-regulated the expression levels of mitochondrial apoptosis-related factors. Furthermore, knockdown of miR-116 attenuated V-induced mitochondrial injury and apoptosis in hepatocytes. In contrast, overexpression of miR-116 and knockdown of CD74 exacerbated mitochondrial injury and apoptosis. BTZO-1 upregulated the CD74 level and alleviated V-induced mitochondrial apoptosis. In summary, V induced mitochondrial damage and apoptosis in duck liver by activating the lncRNA-00742/miR-116/CD74 axis. This research firstly revealed the mechanism of lncRNA-related ceRNAs regulating V-induced mitochondrial apoptosis. [Display omitted] •V exposure altered the expression profiles of lncRNAs and miRNAs in duck liver for the first time.•Excess V induced mitochondrial apoptosis in duck liver.•LncRNA-00742 acted as a molecular sponge for miR-116 and controlled CD74 expression levels.•The lncRNA-00742/miR-116/CD74 axis was found firstly to exist in duck and regulated V-induced mitochondrial apoptosis.