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Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer
BACKGROUND AND OBJECTIVES: Ubiquitin-specific peptidase 28 (USP28) has been reported to play significant roles in several tumors, but its roles in non-small-cell lung cancer (NSCLC) is still unknown. In this study, we aimed to investigate the biological function and molecular mechanisms of USP28 in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396656/ https://www.ncbi.nlm.nih.gov/pubmed/30881015 http://dx.doi.org/10.2147/OTT.S194917 |
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author | Li, Pengling Huang, Ziming Wang, Jipeng Chen, Wei Huang, Jianan |
author_facet | Li, Pengling Huang, Ziming Wang, Jipeng Chen, Wei Huang, Jianan |
author_sort | Li, Pengling |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Ubiquitin-specific peptidase 28 (USP28) has been reported to play significant roles in several tumors, but its roles in non-small-cell lung cancer (NSCLC) is still unknown. In this study, we aimed to investigate the biological function and molecular mechanisms of USP28 in NSCLC. MATERIALS AND METHODS: Immunoblotting analysis was used to detect relative proteins’ expression. Luciferase assay was performed to explore the activation of signal transducer and activator of transcription 3 (STAT3). Immunoprecipitation was performed to assess whether USP28 interacted with STAT3 or deubiquitinated STAT3. Quantitative real-time PCR was performed to evaluate the relative mRNA levels of STAT3 and USP28. Cycloheximide chase assay was carried out to examine whether USP28 affected the half-life of STAT3 protein. Cell Counting Kit-8 assay and xenograft model were used to assess whether USP28 regulated NSCLC cell growth. RESULTS: In this study, the deubiquitinating enzyme USP28 was found to mediate STAT3 signaling in NSCLC cells. USP28 interacted with STAT3, and increased the stability of STAT3 by inducing its deubiquitination. Further studies showed that USP28 was upregulated in both the primary tissues and cell lines of NSCLC. The Kaplan–Meier plotter also indicated that USP28 predicted a poor prognosis of NSCLC patients. Moreover, knockdown of USP28 inhibited cell growth of NSCLC cells in vitro and delayed NSCLC tumor growth in vivo. CONCLUSION: These results demonstrated that USP28 was functional in NSCLC cells, and promoted NSCLC cell growth by inducing STAT3 signaling. This suggests that USP28 could be a novel target for NSCLC therapy. |
format | Online Article Text |
id | pubmed-6396656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63966562019-03-15 Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer Li, Pengling Huang, Ziming Wang, Jipeng Chen, Wei Huang, Jianan Onco Targets Ther Original Research BACKGROUND AND OBJECTIVES: Ubiquitin-specific peptidase 28 (USP28) has been reported to play significant roles in several tumors, but its roles in non-small-cell lung cancer (NSCLC) is still unknown. In this study, we aimed to investigate the biological function and molecular mechanisms of USP28 in NSCLC. MATERIALS AND METHODS: Immunoblotting analysis was used to detect relative proteins’ expression. Luciferase assay was performed to explore the activation of signal transducer and activator of transcription 3 (STAT3). Immunoprecipitation was performed to assess whether USP28 interacted with STAT3 or deubiquitinated STAT3. Quantitative real-time PCR was performed to evaluate the relative mRNA levels of STAT3 and USP28. Cycloheximide chase assay was carried out to examine whether USP28 affected the half-life of STAT3 protein. Cell Counting Kit-8 assay and xenograft model were used to assess whether USP28 regulated NSCLC cell growth. RESULTS: In this study, the deubiquitinating enzyme USP28 was found to mediate STAT3 signaling in NSCLC cells. USP28 interacted with STAT3, and increased the stability of STAT3 by inducing its deubiquitination. Further studies showed that USP28 was upregulated in both the primary tissues and cell lines of NSCLC. The Kaplan–Meier plotter also indicated that USP28 predicted a poor prognosis of NSCLC patients. Moreover, knockdown of USP28 inhibited cell growth of NSCLC cells in vitro and delayed NSCLC tumor growth in vivo. CONCLUSION: These results demonstrated that USP28 was functional in NSCLC cells, and promoted NSCLC cell growth by inducing STAT3 signaling. This suggests that USP28 could be a novel target for NSCLC therapy. Dove Medical Press 2019-02-26 /pmc/articles/PMC6396656/ /pubmed/30881015 http://dx.doi.org/10.2147/OTT.S194917 Text en © 2019 Li et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Li, Pengling Huang, Ziming Wang, Jipeng Chen, Wei Huang, Jianan Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer |
title | Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer |
title_full | Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer |
title_fullStr | Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer |
title_full_unstemmed | Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer |
title_short | Ubiquitin-specific peptidase 28 enhances STAT3 signaling and promotes cell growth in non-small-cell lung cancer |
title_sort | ubiquitin-specific peptidase 28 enhances stat3 signaling and promotes cell growth in non-small-cell lung cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396656/ https://www.ncbi.nlm.nih.gov/pubmed/30881015 http://dx.doi.org/10.2147/OTT.S194917 |
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