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USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition
Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307248/ https://www.ncbi.nlm.nih.gov/pubmed/25547493 http://dx.doi.org/10.3390/ijms16010307 |
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author | Ding, Fangbao Bao, Chunrong Tian, Yue Xiao, Haibo Wang, Mingsong Xie, Xiao Hu, Fengqing Mei, Ju |
author_facet | Ding, Fangbao Bao, Chunrong Tian, Yue Xiao, Haibo Wang, Mingsong Xie, Xiao Hu, Fengqing Mei, Ju |
author_sort | Ding, Fangbao |
collection | PubMed |
description | Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in human NSCLC, as well as normal tissues and cell lines. We then studied the effects of USP22 silencing by shRNA on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. We found that USP22 is overexpressed in human NSCLC tissues and cell lines. USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model. Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway. Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells. Furthermore, MDMX silencing leads to growth arrest and apoptosis in NSCLC cells, and over-expression of MDMX reverses the USP22 silencing-induced effects. Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition. USP22 may represent a novel target for NSCLC treatment. |
format | Online Article Text |
id | pubmed-4307248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43072482015-02-02 USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition Ding, Fangbao Bao, Chunrong Tian, Yue Xiao, Haibo Wang, Mingsong Xie, Xiao Hu, Fengqing Mei, Ju Int J Mol Sci Article Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in human NSCLC, as well as normal tissues and cell lines. We then studied the effects of USP22 silencing by shRNA on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. We found that USP22 is overexpressed in human NSCLC tissues and cell lines. USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model. Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway. Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells. Furthermore, MDMX silencing leads to growth arrest and apoptosis in NSCLC cells, and over-expression of MDMX reverses the USP22 silencing-induced effects. Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition. USP22 may represent a novel target for NSCLC treatment. MDPI 2014-12-25 /pmc/articles/PMC4307248/ /pubmed/25547493 http://dx.doi.org/10.3390/ijms16010307 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ding, Fangbao Bao, Chunrong Tian, Yue Xiao, Haibo Wang, Mingsong Xie, Xiao Hu, Fengqing Mei, Ju USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition |
title | USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition |
title_full | USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition |
title_fullStr | USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition |
title_full_unstemmed | USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition |
title_short | USP22 Promotes NSCLC Tumorigenesis via MDMX Up-Regulation and Subsequent p53 Inhibition |
title_sort | usp22 promotes nsclc tumorigenesis via mdmx up-regulation and subsequent p53 inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307248/ https://www.ncbi.nlm.nih.gov/pubmed/25547493 http://dx.doi.org/10.3390/ijms16010307 |
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