Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784877672069857280 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9873792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT duxuehua usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT keshaobo usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT liangxinyi usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT gaojie usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT xiexiaoxiao usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT qilinzhi usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT liuxueyi usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT xuguoyuan usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT zhangxiaodong usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT durunlei usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization AT lishangze usp14promotescolorectalcancerprogressionbytargetingjnkforstabilization |