A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
Organ size determination is one of the most intriguing unsolved mysteries in biology. Aberrant activation of the major effector and transcription co-activator YAP in the Hippo pathway causes drastic organ enlargement in development and underlies tumorigenesis in many human cancers. However, how robust YAP activation is achieved during organ size control remains elusive. Here we report that the YAP signaling is sustained through a novel microRNA-dependent positive feedback loop. miR-130a, which is directly induced by YAP, could effectively repress VGLL4, an inhibitor of YAP activity, thereby amplifying the YAP signals. Inhibition of miR-130a reversed liver size enlargement induced by Hippo pathway inactivation and blocked YAP-induced tumorigenesis. Furthermore, the Drosophila Hippo pathway target bantam functionally mimics miR-130a by repressing the VGLL4 homolog SdBP/Tgi. These findings reveal an evolutionarily conserved positive feedback mechanism underlying robustness of the Hippo pathway in size control and tumorigenesis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Cell research - 25(2015), 9 vom: 13. Sept., Seite 997-1012 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shen, Shuying [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.06.2016 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/cr.2015.98 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM251821188 |
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| 100 | 1 | |a Shen, Shuying |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Organ size determination is one of the most intriguing unsolved mysteries in biology. Aberrant activation of the major effector and transcription co-activator YAP in the Hippo pathway causes drastic organ enlargement in development and underlies tumorigenesis in many human cancers. However, how robust YAP activation is achieved during organ size control remains elusive. Here we report that the YAP signaling is sustained through a novel microRNA-dependent positive feedback loop. miR-130a, which is directly induced by YAP, could effectively repress VGLL4, an inhibitor of YAP activity, thereby amplifying the YAP signals. Inhibition of miR-130a reversed liver size enlargement induced by Hippo pathway inactivation and blocked YAP-induced tumorigenesis. Furthermore, the Drosophila Hippo pathway target bantam functionally mimics miR-130a by repressing the VGLL4 homolog SdBP/Tgi. These findings reveal an evolutionarily conserved positive feedback mechanism underlying robustness of the Hippo pathway in size control and tumorigenesis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a CCN1 protein, human |2 NLM | |
| 650 | 7 | |a Cysteine-Rich Protein 61 |2 NLM | |
| 650 | 7 | |a Drosophila Proteins |2 NLM | |
| 650 | 7 | |a MIRN130 microRNA, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Phosphoproteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a VGLL4 protein, human |2 NLM | |
| 650 | 7 | |a YAP-Signaling Proteins |2 NLM | |
| 650 | 7 | |a YAP1 protein, human |2 NLM | |
| 650 | 7 | |a Acyltransferases |2 NLM | |
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| 700 | 1 | |a Guo, Xiaocan |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Xinyan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Tingbo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Dawang |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Xin-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jonathan C |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jindan |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Xing-Guo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Bin |e verfasserin |4 aut | |
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