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Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway

Non-small cell lung cancer (NSCLC) is characterized with high morbidity and mortality, mainly due to frequent recurrence and metastasis. However, the underlying molecular mechanisms of NSCLC tumorigenesis are largely unclear. Through data mining in the ONCOMINE and Gene Expression Omnibus (GEO) data...

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Autores principales: Lin, H.C., Li, J., Cheng, D.D., Zhang, X., Yu, T., Zhao, F.Y., Geng, Q., Zhu, M.X., Kong, H.W., Li, H., Yao, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039531/
https://www.ncbi.nlm.nih.gov/pubmed/33869740
http://dx.doi.org/10.1016/j.omto.2021.02.015
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author Lin, H.C.
Li, J.
Cheng, D.D.
Zhang, X.
Yu, T.
Zhao, F.Y.
Geng, Q.
Zhu, M.X.
Kong, H.W.
Li, H.
Yao, M.
author_facet Lin, H.C.
Li, J.
Cheng, D.D.
Zhang, X.
Yu, T.
Zhao, F.Y.
Geng, Q.
Zhu, M.X.
Kong, H.W.
Li, H.
Yao, M.
author_sort Lin, H.C.
collection PubMed
description Non-small cell lung cancer (NSCLC) is characterized with high morbidity and mortality, mainly due to frequent recurrence and metastasis. However, the underlying molecular mechanisms of NSCLC tumorigenesis are largely unclear. Through data mining in the ONCOMINE and Gene Expression Omnibus (GEO) databases, the expression of CSE1L (chromosome segregation like 1 protein/CAS), an exportin, was identified to be significantly upregulated in NSCLC and positively associated with poor prognosis of patients. By use of in vitro and in vivo gain- and loss-of-function experiments, we found that CSE1L can promote NSCLC cell proliferation while inhibiting cell apoptosis. Through immunoprecipitation and mass spectrometry experiments, we demonstrated that CSE1L interacted with RELA (named as P65) and affected its location in the nucleus. Moreover, we found that one of the mechanisms by which CSE1L promotes proliferation and inhibits apoptosis is through activating the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. In summary, our findings indicated an oncogenic role of CSE1L in NSCLC tumorigenesis.
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spelling pubmed-80395312021-04-16 Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway Lin, H.C. Li, J. Cheng, D.D. Zhang, X. Yu, T. Zhao, F.Y. Geng, Q. Zhu, M.X. Kong, H.W. Li, H. Yao, M. Mol Ther Oncolytics Original Article Non-small cell lung cancer (NSCLC) is characterized with high morbidity and mortality, mainly due to frequent recurrence and metastasis. However, the underlying molecular mechanisms of NSCLC tumorigenesis are largely unclear. Through data mining in the ONCOMINE and Gene Expression Omnibus (GEO) databases, the expression of CSE1L (chromosome segregation like 1 protein/CAS), an exportin, was identified to be significantly upregulated in NSCLC and positively associated with poor prognosis of patients. By use of in vitro and in vivo gain- and loss-of-function experiments, we found that CSE1L can promote NSCLC cell proliferation while inhibiting cell apoptosis. Through immunoprecipitation and mass spectrometry experiments, we demonstrated that CSE1L interacted with RELA (named as P65) and affected its location in the nucleus. Moreover, we found that one of the mechanisms by which CSE1L promotes proliferation and inhibits apoptosis is through activating the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. In summary, our findings indicated an oncogenic role of CSE1L in NSCLC tumorigenesis. American Society of Gene & Cell Therapy 2021-03-10 /pmc/articles/PMC8039531/ /pubmed/33869740 http://dx.doi.org/10.1016/j.omto.2021.02.015 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Lin, H.C.
Li, J.
Cheng, D.D.
Zhang, X.
Yu, T.
Zhao, F.Y.
Geng, Q.
Zhu, M.X.
Kong, H.W.
Li, H.
Yao, M.
Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
title Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
title_full Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
title_fullStr Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
title_full_unstemmed Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
title_short Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
title_sort nuclear export protein cse1l interacts with p65 and promotes nsclc growth via nf-κb/mapk pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039531/
https://www.ncbi.nlm.nih.gov/pubmed/33869740
http://dx.doi.org/10.1016/j.omto.2021.02.015
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