MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling

PloS One
Ya-Wen LiJen-Leih Wu

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 ...Continue Reading

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Citations

Jan 9, 2019·Journal of Cellular and Molecular Medicine·Edward SeclamanAndrei Anghel
Dec 7, 2019·Cancers·Francesca FornariCatia Giovannini
Aug 21, 2019·Gene·Satheeswaran BalasubramanianEkambaram Perumal

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Methods Mentioned

BETA
transgenic
antisense oligonucleotides
transfections
in vitro transcription
PCR
Fluorescence

Software Mentioned

Imaris
RNAhybrid
TargetScan
MicroInspector
SPOT image

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