ZFIN ID: ZDB-PUB-170523-1
MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling
Li, Y.W., Chiang, K.Y., Li, Y.H., Wu, S.Y., Liu, W., Lin, C.R., Wu, J.L.
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
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.