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LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma
Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) is a tumour suppressor gene in nasopharyngeal carcinoma (NPC), and low expression of LPLUNC1 is associated with poor prognosis. Our previous study showed that LPLUNC1 upregulates Prohibitin 1 (PHB1), a pleiotropic protein that functions as a t...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756001/ https://www.ncbi.nlm.nih.gov/pubmed/30886235 http://dx.doi.org/10.1038/s41388-019-0778-6 |
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author | Wang, Heran Zhou, Yujuan Oyang, Linda Han, Yaqian Xia, Longzheng Lin, Jingguan Tang, Yanyan Su, Min Tan, Shiming Tian, Yutong Chen, Xiaoyan Luo, Xia Liang, Jiaxin Rao, Shan Wang, Ying Xiong, Wei Zeng, Zhaoyang Wang, Hui Li, Guiyuan Liao, Qianjin |
author_facet | Wang, Heran Zhou, Yujuan Oyang, Linda Han, Yaqian Xia, Longzheng Lin, Jingguan Tang, Yanyan Su, Min Tan, Shiming Tian, Yutong Chen, Xiaoyan Luo, Xia Liang, Jiaxin Rao, Shan Wang, Ying Xiong, Wei Zeng, Zhaoyang Wang, Hui Li, Guiyuan Liao, Qianjin |
author_sort | Wang, Heran |
collection | PubMed |
description | Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) is a tumour suppressor gene in nasopharyngeal carcinoma (NPC), and low expression of LPLUNC1 is associated with poor prognosis. Our previous study showed that LPLUNC1 upregulates Prohibitin 1 (PHB1), a pleiotropic protein that functions as a tumour suppressor gene in various cancers. Low expression of PHB1 was also found to be associated with the poor prognosis of NPC patients. However, the mechanisms by which LPLUNC1 upregulates PHB1 and the potential role of PHB1 in NPC are unclear. Here, we found that LPLUNC1 stabilised PHB1 by inhibiting PHB1 ubiquitination, which is mediated by E3 ligase TRIM21. LPLUNC1 competitively impaired the binding of PHB1 to TRIM21 due to its stronger binding affinity to PHB1, suppressing the ubiquitination of PHB1. Therefore, our study indicates that PHB1 acted as a tumour suppressor gene by inhibiting NF-κB activity. Depletion of PHB1 significantly attenuated the anti-tumour effects of LPLUNC1 in NPC cells, and the inhibitory effect of LPLUNC1 on NF-κB activity was thus reversed. Together, our findings revealed a novel mechanism underlying the anticancer effect of LPLUNC1 and clarified that PHB1 may represent a novel, promising candidate tumour suppressor gene in NPC, with potential therapeutic target value. |
format | Online Article Text |
id | pubmed-6756001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67560012019-09-24 LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma Wang, Heran Zhou, Yujuan Oyang, Linda Han, Yaqian Xia, Longzheng Lin, Jingguan Tang, Yanyan Su, Min Tan, Shiming Tian, Yutong Chen, Xiaoyan Luo, Xia Liang, Jiaxin Rao, Shan Wang, Ying Xiong, Wei Zeng, Zhaoyang Wang, Hui Li, Guiyuan Liao, Qianjin Oncogene Article Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) is a tumour suppressor gene in nasopharyngeal carcinoma (NPC), and low expression of LPLUNC1 is associated with poor prognosis. Our previous study showed that LPLUNC1 upregulates Prohibitin 1 (PHB1), a pleiotropic protein that functions as a tumour suppressor gene in various cancers. Low expression of PHB1 was also found to be associated with the poor prognosis of NPC patients. However, the mechanisms by which LPLUNC1 upregulates PHB1 and the potential role of PHB1 in NPC are unclear. Here, we found that LPLUNC1 stabilised PHB1 by inhibiting PHB1 ubiquitination, which is mediated by E3 ligase TRIM21. LPLUNC1 competitively impaired the binding of PHB1 to TRIM21 due to its stronger binding affinity to PHB1, suppressing the ubiquitination of PHB1. Therefore, our study indicates that PHB1 acted as a tumour suppressor gene by inhibiting NF-κB activity. Depletion of PHB1 significantly attenuated the anti-tumour effects of LPLUNC1 in NPC cells, and the inhibitory effect of LPLUNC1 on NF-κB activity was thus reversed. Together, our findings revealed a novel mechanism underlying the anticancer effect of LPLUNC1 and clarified that PHB1 may represent a novel, promising candidate tumour suppressor gene in NPC, with potential therapeutic target value. Nature Publishing Group UK 2019-03-18 2019 /pmc/articles/PMC6756001/ /pubmed/30886235 http://dx.doi.org/10.1038/s41388-019-0778-6 Text en © The Author(s) 2019 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 Wang, Heran Zhou, Yujuan Oyang, Linda Han, Yaqian Xia, Longzheng Lin, Jingguan Tang, Yanyan Su, Min Tan, Shiming Tian, Yutong Chen, Xiaoyan Luo, Xia Liang, Jiaxin Rao, Shan Wang, Ying Xiong, Wei Zeng, Zhaoyang Wang, Hui Li, Guiyuan Liao, Qianjin LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma |
title | LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma |
title_full | LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma |
title_fullStr | LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma |
title_full_unstemmed | LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma |
title_short | LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma |
title_sort | lplunc1 stabilises phb1 by counteracting trim21-mediated ubiquitination to inhibit nf-κb activity in nasopharyngeal carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756001/ https://www.ncbi.nlm.nih.gov/pubmed/30886235 http://dx.doi.org/10.1038/s41388-019-0778-6 |
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