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The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma
OTU domain-containing protein 3 (OTUD3), a deubiquitinating enzyme, has been shown to participate in progression of multiple malignancies. The accurate function of OTUD3 in hepatocellular carcinoma (HCC) progression remains elusive. We found that OTUD3 was significantly overexpressed in HCC, and hig...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386523/ https://www.ncbi.nlm.nih.gov/pubmed/34380780 http://dx.doi.org/10.18632/aging.203293 |
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author | Xie, Peiyi Chen, Yanglin Zhang, Hongfei Zhou, Guichao Chao, Qing Wang, Jiangwen Liu, Yue Fang, Jiayu Xie, Jing Zhen, Jing Wang, Zhiyuan Hao, Liang Huang, Da |
author_facet | Xie, Peiyi Chen, Yanglin Zhang, Hongfei Zhou, Guichao Chao, Qing Wang, Jiangwen Liu, Yue Fang, Jiayu Xie, Jing Zhen, Jing Wang, Zhiyuan Hao, Liang Huang, Da |
author_sort | Xie, Peiyi |
collection | PubMed |
description | OTU domain-containing protein 3 (OTUD3), a deubiquitinating enzyme, has been shown to participate in progression of multiple malignancies. The accurate function of OTUD3 in hepatocellular carcinoma (HCC) progression remains elusive. We found that OTUD3 was significantly overexpressed in HCC, and higher OTUD3 expression was correlated with larger tumor size, more distant metastasis, and worse TNM stage. A series of gain- and loss-of-function assays were also performed to examine the oncogenic function of OTUD3 in promoting HCC cell growth and metastasis in vitro. Using a xenograft mouse model, we showed that OTUD3 accelerated HCC progression in vivo. Furthermore, alpha-actinin 4 (ACTN4) was identified as a downstream target of OTUD3 through mass spectrometry analysis, and the ACTN4 protein level was significantly related to OTUD3 expression. Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it. Finally, ACTN4 was found to be essential for OTUD3-mediated HCC proliferation and metastasis in vitro and in vivo. Collectively, our findings identify the oncogenic role of OTUD3 in HCC and suggest that OTUD3 can be considered as a pivotal prognostic biomarker and a potential therapeutic target. |
format | Online Article Text |
id | pubmed-8386523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-83865232021-08-27 The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma Xie, Peiyi Chen, Yanglin Zhang, Hongfei Zhou, Guichao Chao, Qing Wang, Jiangwen Liu, Yue Fang, Jiayu Xie, Jing Zhen, Jing Wang, Zhiyuan Hao, Liang Huang, Da Aging (Albany NY) Research Paper OTU domain-containing protein 3 (OTUD3), a deubiquitinating enzyme, has been shown to participate in progression of multiple malignancies. The accurate function of OTUD3 in hepatocellular carcinoma (HCC) progression remains elusive. We found that OTUD3 was significantly overexpressed in HCC, and higher OTUD3 expression was correlated with larger tumor size, more distant metastasis, and worse TNM stage. A series of gain- and loss-of-function assays were also performed to examine the oncogenic function of OTUD3 in promoting HCC cell growth and metastasis in vitro. Using a xenograft mouse model, we showed that OTUD3 accelerated HCC progression in vivo. Furthermore, alpha-actinin 4 (ACTN4) was identified as a downstream target of OTUD3 through mass spectrometry analysis, and the ACTN4 protein level was significantly related to OTUD3 expression. Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it. Finally, ACTN4 was found to be essential for OTUD3-mediated HCC proliferation and metastasis in vitro and in vivo. Collectively, our findings identify the oncogenic role of OTUD3 in HCC and suggest that OTUD3 can be considered as a pivotal prognostic biomarker and a potential therapeutic target. Impact Journals 2021-08-10 /pmc/articles/PMC8386523/ /pubmed/34380780 http://dx.doi.org/10.18632/aging.203293 Text en Copyright: © 2021 Xie et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xie, Peiyi Chen, Yanglin Zhang, Hongfei Zhou, Guichao Chao, Qing Wang, Jiangwen Liu, Yue Fang, Jiayu Xie, Jing Zhen, Jing Wang, Zhiyuan Hao, Liang Huang, Da The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma |
title | The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma |
title_full | The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma |
title_fullStr | The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma |
title_full_unstemmed | The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma |
title_short | The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma |
title_sort | deubiquitinase otud3 stabilizes actn4 to drive growth and metastasis of hepatocellular carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386523/ https://www.ncbi.nlm.nih.gov/pubmed/34380780 http://dx.doi.org/10.18632/aging.203293 |
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