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ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression
Our previous work demonstrated that Epithelial Splicing Regulatory Protein 1 (ESRP1) could inhibit the progression of lung adenocarcinoma (ADC). When ESRP1 was upregulated, the interferon (IFN) pathway was activated and Interferon-stimulated gene 15 (ISG15) expression increased exponentially in our...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343783/ https://www.ncbi.nlm.nih.gov/pubmed/32641707 http://dx.doi.org/10.1038/s41419-020-2706-7 |
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author | Qu, Tongyuan Zhang, Wenshuai Qi, Lisha Cao, Lu Liu, Changxu Huang, Qiujuan Li, Guangning Li, Lingmei Wang, Yalei Guo, Qianru Guo, Yuhong Ren, Danyang Gao, Yanan Wang, Jinpeng Meng, Bin Zhang, Bin Cao, Wenfeng |
author_facet | Qu, Tongyuan Zhang, Wenshuai Qi, Lisha Cao, Lu Liu, Changxu Huang, Qiujuan Li, Guangning Li, Lingmei Wang, Yalei Guo, Qianru Guo, Yuhong Ren, Danyang Gao, Yanan Wang, Jinpeng Meng, Bin Zhang, Bin Cao, Wenfeng |
author_sort | Qu, Tongyuan |
collection | PubMed |
description | Our previous work demonstrated that Epithelial Splicing Regulatory Protein 1 (ESRP1) could inhibit the progression of lung adenocarcinoma (ADC). When ESRP1 was upregulated, the interferon (IFN) pathway was activated and Interferon-stimulated gene 15 (ISG15) expression increased exponentially in our microarray result. In this study, we aim to explore the function of ISG15 and its interactions with ESRP1 and to provide new insights for ADC treatment. ISG15 expression in lung ADC tissues was determined by immunohistochemistry (IHC) staining. The effect of ISG15 on lung ADC progression was examined by in vitro and in vivo assays. The mechanism of action on ESRP1 regulating ISG15 was investigated using Western blotting, RT-qPCR, immunofluorescence staining, chromatin immunoprecipitation, and a dual luciferase reporter system. The ISGylation between ISG15 and ESRP1 was detected by co-immunoprecipitation. Patients with high ISG15 expression were associated with higher survival rates, especially those with ISG15 expression in the nucleus. In vitro and in vivo experiments showed that upregulation of ISG15 inhibited EMT in lung ADC. ESRP1 upregulated the expression of ISG15 through CREB with enriched ISG15 in the nucleus. Importantly, ISG15 promoted ISGylation of ESRP1 and slowed the degradation of ESRP1, which demonstrated that ESRP1 and ISG15 formed a positive feedback loop and jointly suppressed EMT of lung ADC. In conclusion, ISG15 serves as an independent prognostic marker for long-term survival in lung ADC patients. We have revealed the protective effect of ISG15 against lung ADC progression and the combinatorial benefit of ISG15 and ESRP1 on inhibiting EMT. These findings suggest that reconstituting ISG15 and ESRP1 may have the potential for treating lung ADC. |
format | Online Article Text |
id | pubmed-7343783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73437832020-07-13 ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression Qu, Tongyuan Zhang, Wenshuai Qi, Lisha Cao, Lu Liu, Changxu Huang, Qiujuan Li, Guangning Li, Lingmei Wang, Yalei Guo, Qianru Guo, Yuhong Ren, Danyang Gao, Yanan Wang, Jinpeng Meng, Bin Zhang, Bin Cao, Wenfeng Cell Death Dis Article Our previous work demonstrated that Epithelial Splicing Regulatory Protein 1 (ESRP1) could inhibit the progression of lung adenocarcinoma (ADC). When ESRP1 was upregulated, the interferon (IFN) pathway was activated and Interferon-stimulated gene 15 (ISG15) expression increased exponentially in our microarray result. In this study, we aim to explore the function of ISG15 and its interactions with ESRP1 and to provide new insights for ADC treatment. ISG15 expression in lung ADC tissues was determined by immunohistochemistry (IHC) staining. The effect of ISG15 on lung ADC progression was examined by in vitro and in vivo assays. The mechanism of action on ESRP1 regulating ISG15 was investigated using Western blotting, RT-qPCR, immunofluorescence staining, chromatin immunoprecipitation, and a dual luciferase reporter system. The ISGylation between ISG15 and ESRP1 was detected by co-immunoprecipitation. Patients with high ISG15 expression were associated with higher survival rates, especially those with ISG15 expression in the nucleus. In vitro and in vivo experiments showed that upregulation of ISG15 inhibited EMT in lung ADC. ESRP1 upregulated the expression of ISG15 through CREB with enriched ISG15 in the nucleus. Importantly, ISG15 promoted ISGylation of ESRP1 and slowed the degradation of ESRP1, which demonstrated that ESRP1 and ISG15 formed a positive feedback loop and jointly suppressed EMT of lung ADC. In conclusion, ISG15 serves as an independent prognostic marker for long-term survival in lung ADC patients. We have revealed the protective effect of ISG15 against lung ADC progression and the combinatorial benefit of ISG15 and ESRP1 on inhibiting EMT. These findings suggest that reconstituting ISG15 and ESRP1 may have the potential for treating lung ADC. Nature Publishing Group UK 2020-07-02 /pmc/articles/PMC7343783/ /pubmed/32641707 http://dx.doi.org/10.1038/s41419-020-2706-7 Text en © The Author(s) 2020 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/. |
spellingShingle | Article Qu, Tongyuan Zhang, Wenshuai Qi, Lisha Cao, Lu Liu, Changxu Huang, Qiujuan Li, Guangning Li, Lingmei Wang, Yalei Guo, Qianru Guo, Yuhong Ren, Danyang Gao, Yanan Wang, Jinpeng Meng, Bin Zhang, Bin Cao, Wenfeng ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression |
title | ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression |
title_full | ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression |
title_fullStr | ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression |
title_full_unstemmed | ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression |
title_short | ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression |
title_sort | isg15 induces esrp1 to inhibit lung adenocarcinoma progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343783/ https://www.ncbi.nlm.nih.gov/pubmed/32641707 http://dx.doi.org/10.1038/s41419-020-2706-7 |
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