PUBLICATION
Up-stream mechanisms for up-regulation of miR-125b from triclosan exposure to zebrafish (Danio rerio)
- Authors
- Lin, J., Wang, C., Liu, J., Dahlgren, R.A., Ai, W., Zeng, A., Wang, X., Wang, H.
- ID
- ZDB-PUB-171110-2
- Date
- 2017
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 193: 256-267 (Journal)
- Registered Authors
- Keywords
- G protein-coupled receptor, Lipid metabolism, Promoter activity, Triclosan, Up-regulation of miR-125b
- MeSH Terms
-
- Animals
- Anti-Infective Agents/toxicity*
- Binding Sites
- Endocrine Disruptors/toxicity*
- Estrogen Receptor alpha/metabolism
- Estrogen Receptor beta/metabolism
- Humans
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- NF-E2-Related Factor 2/metabolism
- Promoter Regions, Genetic
- Triclosan/toxicity*
- Up-Regulation
- Water Pollutants, Chemical/toxicity*
- Zebrafish/metabolism*
- PubMed
- 29121543 Full text @ Aquat. Toxicol.
Citation
Lin, J., Wang, C., Liu, J., Dahlgren, R.A., Ai, W., Zeng, A., Wang, X., Wang, H. (2017) Up-stream mechanisms for up-regulation of miR-125b from triclosan exposure to zebrafish (Danio rerio). Aquatic toxicology (Amsterdam, Netherlands). 193:256-267.
Abstract
Triclosan (TCS) exposure has widely adverse biological effects such as influencing biological reproduction and endocrine disorders. While some studies have addressed TCS-induced expression changes of miRNAs and their related down-stream target genes, no data are available concerning how TCS impairs miRNA expression leading us to study up-stream regulating mechanisms. Four miRNAs (miR-125b, miR-205, miR-142a and miR-203a) showed differential expression between TCS-exposure treatments and the control group; their functions mainly involved fatty acid synthesis and metabolism. TCS exposure led to the up-regulation of mature miR-125b that was concomitant with consistent changes in pri-mir-125b-1 and pri-mir-125b-3 among its 3 pri-mir-125bs. Up-regulation of miR-125b originated from direct shear processes involving the two up-regulated precursors, but not pri-mir-125b2. Increased expression of pri-mir-125b-1 and pri-mir-125b-3 resulted from nfe2l2- and c/ebpα-integration with positive control elements of promoters for the two precursors. The overexpression of transcriptional factors, nfe2l2 and c/ebpα, initiated the promoter activity for the miR-125b precursor. CpG islands and Nfe2l2 were involved in constitutive expression of mir-125b-1 and mir-125b-3. The activities of two promoter regions, -487 to -1bp for pri-mir-125b1 and -1327 to +14bp for pri-mir-125b-3 having binding sites for NFE2 and Nfe2l2/MAF:NFE2, were higher than other regions, further demonstrating that the transcriptional factor Nfe2l2 was involved in the regulation of pri-mir-125b1 and pri-mir-125b-3. TCS's estrogen activity resulted from its effects on GPER, a novel membrane receptor, rather than the classical ERα and ERβ. These results explain, to some extent, the up-stream mechanism for miR-125b up-regulation, and also provide a guidance to future mechanistic study on TCS-exposure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping