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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 robu...

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Autores principales: Shen, Shuying, Guo, Xiaocan, Yan, Huan, Lu, Yi, Ji, Xinyan, Li, Li, Liang, Tingbo, Zhou, Dawang, Feng, Xin-Hua, Zhao, Jonathan C, Yu, Jindan, Gong, Xing-Guo, Zhang, Lei, Zhao, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559818/
https://www.ncbi.nlm.nih.gov/pubmed/26272168
http://dx.doi.org/10.1038/cr.2015.98
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author Shen, Shuying
Guo, Xiaocan
Yan, Huan
Lu, Yi
Ji, Xinyan
Li, Li
Liang, Tingbo
Zhou, Dawang
Feng, Xin-Hua
Zhao, Jonathan C
Yu, Jindan
Gong, Xing-Guo
Zhang, Lei
Zhao, Bin
author_facet Shen, Shuying
Guo, Xiaocan
Yan, Huan
Lu, Yi
Ji, Xinyan
Li, Li
Liang, Tingbo
Zhou, Dawang
Feng, Xin-Hua
Zhao, Jonathan C
Yu, Jindan
Gong, Xing-Guo
Zhang, Lei
Zhao, Bin
author_sort Shen, Shuying
collection PubMed
description 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.
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spelling pubmed-45598182015-09-14 A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis Shen, Shuying Guo, Xiaocan Yan, Huan Lu, Yi Ji, Xinyan Li, Li Liang, Tingbo Zhou, Dawang Feng, Xin-Hua Zhao, Jonathan C Yu, Jindan Gong, Xing-Guo Zhang, Lei Zhao, Bin Cell Res Original Article 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. Nature Publishing Group 2015-09 2015-08-14 /pmc/articles/PMC4559818/ /pubmed/26272168 http://dx.doi.org/10.1038/cr.2015.98 Text en Copyright © 2015 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences http://creativecommons.org/licenses/by-nc-nd/3.0 This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0
spellingShingle Original Article
Shen, Shuying
Guo, Xiaocan
Yan, Huan
Lu, Yi
Ji, Xinyan
Li, Li
Liang, Tingbo
Zhou, Dawang
Feng, Xin-Hua
Zhao, Jonathan C
Yu, Jindan
Gong, Xing-Guo
Zhang, Lei
Zhao, Bin
A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
title A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
title_full A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
title_fullStr A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
title_full_unstemmed A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
title_short A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis
title_sort mir-130a-yap positive feedback loop promotes organ size and tumorigenesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559818/
https://www.ncbi.nlm.nih.gov/pubmed/26272168
http://dx.doi.org/10.1038/cr.2015.98
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