MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling.
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-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5439702?pdf=render |
| _version_ | 1828169209579831296 |
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| author | Ya-Wen Li Keng-Yu Chiang Yen-Hsing Li Sung-Yu Wu Wangta Liu Chia-Ray Lin Jen-Leih Wu |
| author_facet | Ya-Wen Li Keng-Yu Chiang Yen-Hsing Li Sung-Yu Wu Wangta Liu Chia-Ray Lin Jen-Leih Wu |
| author_sort | Ya-Wen Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:47:28Z |
| format | Article |
| id | doaj.art-4f921781cc7b4a6084796600c114688d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T02:47:28Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4f921781cc7b4a6084796600c114688d2022-12-22T03:51:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017788710.1371/journal.pone.0177887MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling.Ya-Wen LiKeng-Yu ChiangYen-Hsing LiSung-Yu WuWangta LiuChia-Ray LinJen-Leih WuMicroRNAs (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.http://europepmc.org/articles/PMC5439702?pdf=render |
| spellingShingle | Ya-Wen Li Keng-Yu Chiang Yen-Hsing Li Sung-Yu Wu Wangta Liu Chia-Ray Lin Jen-Leih Wu MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. PLoS ONE |
| title | MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. |
| title_full | MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. |
| title_fullStr | MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. |
| title_full_unstemmed | MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. |
| title_short | MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling. |
| title_sort | mir 145 mediates zebrafish hepatic outgrowth through progranulin a signaling |
| url | http://europepmc.org/articles/PMC5439702?pdf=render |
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