The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer

Our previous studies revealed that oncogene CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), and it could be regulated by micro RNAs. But no direct role of post-translational modification of CPNE1 in N...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Ruochen, Zhang, Weijie, Zeng, Yuanyuan, Li, Yue, Zhou, Jieqi, Zhang, Yang, Wang, Anqi, Lv, Yantian, Zhu, Jianjie, Liu, Zeyi, Huang, Jian-an
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572224/
https://www.ncbi.nlm.nih.gov/pubmed/34743202
http://dx.doi.org/10.1038/s41420-021-00736-1
_version_ 1784595179103059968
author Zhang, Ruochen
Zhang, Weijie
Zeng, Yuanyuan
Li, Yue
Zhou, Jieqi
Zhang, Yang
Wang, Anqi
Lv, Yantian
Zhu, Jianjie
Liu, Zeyi
Huang, Jian-an
author_facet Zhang, Ruochen
Zhang, Weijie
Zeng, Yuanyuan
Li, Yue
Zhou, Jieqi
Zhang, Yang
Wang, Anqi
Lv, Yantian
Zhu, Jianjie
Liu, Zeyi
Huang, Jian-an
author_sort Zhang, Ruochen
collection PubMed
description Our previous studies revealed that oncogene CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), and it could be regulated by micro RNAs. But no direct role of post-translational modification of CPNE1 in NSCLC has been reported. This study confirms that CPNE1 is degraded by two pathways: the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. CPNE1 binds with the ubiquitin molecule via its K157 residue. Moreover, we determined that the ubiquitin ligase NEDD4L can mediate the ubiquitination of CPNE1 and promote its degradation. In addition, we find that NEDD4L knockdown promotes the proliferation and metastasis of NSCLC cells by regulating CPNE1 in vitro and vivo. This study aims to further investigate the mechanism of CPNE1 ubiquitination in the occurrence and development of NSCLC and provide a new potential target for NSCLC treatment.
format Online
Article
Text
id pubmed-8572224
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-85722242021-11-19 The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer Zhang, Ruochen Zhang, Weijie Zeng, Yuanyuan Li, Yue Zhou, Jieqi Zhang, Yang Wang, Anqi Lv, Yantian Zhu, Jianjie Liu, Zeyi Huang, Jian-an Cell Death Discov Article Our previous studies revealed that oncogene CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), and it could be regulated by micro RNAs. But no direct role of post-translational modification of CPNE1 in NSCLC has been reported. This study confirms that CPNE1 is degraded by two pathways: the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. CPNE1 binds with the ubiquitin molecule via its K157 residue. Moreover, we determined that the ubiquitin ligase NEDD4L can mediate the ubiquitination of CPNE1 and promote its degradation. In addition, we find that NEDD4L knockdown promotes the proliferation and metastasis of NSCLC cells by regulating CPNE1 in vitro and vivo. This study aims to further investigate the mechanism of CPNE1 ubiquitination in the occurrence and development of NSCLC and provide a new potential target for NSCLC treatment. Nature Publishing Group UK 2021-11-06 /pmc/articles/PMC8572224/ /pubmed/34743202 http://dx.doi.org/10.1038/s41420-021-00736-1 Text en © The Author(s) 2021 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
Zhang, Ruochen
Zhang, Weijie
Zeng, Yuanyuan
Li, Yue
Zhou, Jieqi
Zhang, Yang
Wang, Anqi
Lv, Yantian
Zhu, Jianjie
Liu, Zeyi
Huang, Jian-an
The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer
title The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer
title_full The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer
title_fullStr The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer
title_full_unstemmed The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer
title_short The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer
title_sort regulation of cpne1 ubiquitination by the nedd4l is involved in the pathogenesis of non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572224/
https://www.ncbi.nlm.nih.gov/pubmed/34743202
http://dx.doi.org/10.1038/s41420-021-00736-1
work_keys_str_mv AT zhangruochen theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhangweijie theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zengyuanyuan theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT liyue theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhoujieqi theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhangyang theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT wanganqi theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT lvyantian theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhujianjie theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT liuzeyi theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT huangjianan theregulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhangruochen regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhangweijie regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zengyuanyuan regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT liyue regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhoujieqi regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhangyang regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT wanganqi regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT lvyantian regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT zhujianjie regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT liuzeyi regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer
AT huangjianan regulationofcpne1ubiquitinationbythenedd4lisinvolvedinthepathogenesisofnonsmallcelllungcancer

Ejemplares similares