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USP14 promotes colorectal cancer progression by targeting JNK for stabilization

MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiqui...

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Autores principales: Du, Xue-Hua, Ke, Shao-Bo, Liang, Xin-Yi, Gao, Jie, Xie, Xiao-Xiao, Qi, Lin-Zhi, Liu, Xue-Yi, Xu, Guo-Yuan, Zhang, Xiao-Dong, Du, Run-Lei, Li, Shang-Ze
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873792/
https://www.ncbi.nlm.nih.gov/pubmed/36693850
http://dx.doi.org/10.1038/s41419-023-05579-5
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author Du, Xue-Hua
Ke, Shao-Bo
Liang, Xin-Yi
Gao, Jie
Xie, Xiao-Xiao
Qi, Lin-Zhi
Liu, Xue-Yi
Xu, Guo-Yuan
Zhang, Xiao-Dong
Du, Run-Lei
Li, Shang-Ze
author_facet Du, Xue-Hua
Ke, Shao-Bo
Liang, Xin-Yi
Gao, Jie
Xie, Xiao-Xiao
Qi, Lin-Zhi
Liu, Xue-Yi
Xu, Guo-Yuan
Zhang, Xiao-Dong
Du, Run-Lei
Li, Shang-Ze
author_sort Du, Xue-Hua
collection PubMed
description MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiquitinase that interacts and stabilizes JNK. USP14 is elevated in colorectal cancer patients and is positively associated with JNK protein and downstream gene expression. USP14 ablation reduces cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by downregulating MAPK/JNK pathway activation. Moreover, USP14 expression is induced by TNF-α, forming a feedback loop with JNK and leading to tumor amplification. Our study suggests that elevated expression of USP14 promotes MAPK/JNK signaling by stabilizing JNK, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased USP14 expression.
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spelling pubmed-98737922023-01-26 USP14 promotes colorectal cancer progression by targeting JNK for stabilization Du, Xue-Hua Ke, Shao-Bo Liang, Xin-Yi Gao, Jie Xie, Xiao-Xiao Qi, Lin-Zhi Liu, Xue-Yi Xu, Guo-Yuan Zhang, Xiao-Dong Du, Run-Lei Li, Shang-Ze Cell Death Dis Article MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiquitinase that interacts and stabilizes JNK. USP14 is elevated in colorectal cancer patients and is positively associated with JNK protein and downstream gene expression. USP14 ablation reduces cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by downregulating MAPK/JNK pathway activation. Moreover, USP14 expression is induced by TNF-α, forming a feedback loop with JNK and leading to tumor amplification. Our study suggests that elevated expression of USP14 promotes MAPK/JNK signaling by stabilizing JNK, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased USP14 expression. Nature Publishing Group UK 2023-01-24 /pmc/articles/PMC9873792/ /pubmed/36693850 http://dx.doi.org/10.1038/s41419-023-05579-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Du, Xue-Hua
Ke, Shao-Bo
Liang, Xin-Yi
Gao, Jie
Xie, Xiao-Xiao
Qi, Lin-Zhi
Liu, Xue-Yi
Xu, Guo-Yuan
Zhang, Xiao-Dong
Du, Run-Lei
Li, Shang-Ze
USP14 promotes colorectal cancer progression by targeting JNK for stabilization
title USP14 promotes colorectal cancer progression by targeting JNK for stabilization
title_full USP14 promotes colorectal cancer progression by targeting JNK for stabilization
title_fullStr USP14 promotes colorectal cancer progression by targeting JNK for stabilization
title_full_unstemmed USP14 promotes colorectal cancer progression by targeting JNK for stabilization
title_short USP14 promotes colorectal cancer progression by targeting JNK for stabilization
title_sort usp14 promotes colorectal cancer progression by targeting jnk for stabilization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873792/
https://www.ncbi.nlm.nih.gov/pubmed/36693850
http://dx.doi.org/10.1038/s41419-023-05579-5
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