PUBLICATION
MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling
- Authors
- Li, Y.W., Chiang, K.Y., Li, Y.H., Wu, S.Y., Liu, W., Lin, C.R., Wu, J.L.
- ID
- ZDB-PUB-170523-1
- Date
- 2017
- Source
- PLoS One 12: e0177887 (Journal)
- Registered Authors
- Wu, Jen-Leih
- Keywords
- Embryos, Zebrafish, MicroRNAs, Liver development, Green fluorescent protein, Hepatocytes, Gene expression, Luciferase
- MeSH Terms
-
- Animals
- Cell Line
- Cell Proliferation
- Gene Expression Regulation, Developmental
- Hepatocytes/cytology
- Intercellular Signaling Peptides and Proteins/genetics*
- Liver/growth & development*
- MicroRNAs/genetics*
- Organ Size
- Signal Transduction
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 28531199 Full text @ PLoS One
Citation
Li, Y.W., Chiang, K.Y., Li, Y.H., Wu, S.Y., Liu, W., Lin, C.R., Wu, J.L. (2017) MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. PLoS One. 12:e0177887.
Abstract
MicroRNAs (miRs) are mRNA-regulatory molecules that fine-tune gene expression and modulate both processes of development and tumorigenesis. Our previous studies identified progranulin A (GrnA) as a growth factor which induces zebrafish hepatic outgrowth through MET signaling. We also found that miR-145 is one of potential fine-tuning regulators of GrnA involved in embryonic hepatic outgrowth. The low level of miR-145 seen in hepatocarinogenesis has been shown to promote pathological liver growth. However, little is known about the regulatory mechanism of miR-145 in embryonic liver development. In this study, we demonstrate a significant decrease in miR-145 expression during hepatogenesis. We modulate miR-145 expression in zebrafish embryos by injection with a miR-145 mimic or a miR-145 hairpin inhibitor. Altered embryonic liver outgrowth is observed in response to miR-145 expression modulation. We also confirm a critical role of miR-145 in hepatic outgrowth by using whole-mount in situ hybridization. Loss of miR-145 expression in embryos results in hepatic cell proliferation, and vice versa. Furthermore, we demonstrate that GrnA is a target of miR-145 and GrnA-induced MET signaling is also regulated by miR-145 as determined by luciferase reporter assay and gene expression analysis, respectively. In addition, co-injection of GrnA mRNA with miR-145 mimic or MO-GrnA with miR-145 inhibitor restores the liver defects caused by dysregulation of miR-145 expression. In conclusion, our findings suggest an important role of miR-145 in regulating GrnA-dependent hepatic outgrowth in zebrafish embryonic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping