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USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma

In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was exam...

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Autores principales: Zhao, Guang-Yin, Lin, Zong-Wu, Lu, Chun-Lai, Gu, Jie, Yuan, Yun-Feng, Xu, Feng-Kai, Liu, Rong-Hua, Ge, Di, Ding, Jian-Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375295/
https://www.ncbi.nlm.nih.gov/pubmed/25519684
http://dx.doi.org/10.1007/s13277-014-2773-4
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author Zhao, Guang-Yin
Lin, Zong-Wu
Lu, Chun-Lai
Gu, Jie
Yuan, Yun-Feng
Xu, Feng-Kai
Liu, Rong-Hua
Ge, Di
Ding, Jian-Yong
author_facet Zhao, Guang-Yin
Lin, Zong-Wu
Lu, Chun-Lai
Gu, Jie
Yuan, Yun-Feng
Xu, Feng-Kai
Liu, Rong-Hua
Ge, Di
Ding, Jian-Yong
author_sort Zhao, Guang-Yin
collection PubMed
description In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13277-014-2773-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-43752952015-04-21 USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma Zhao, Guang-Yin Lin, Zong-Wu Lu, Chun-Lai Gu, Jie Yuan, Yun-Feng Xu, Feng-Kai Liu, Rong-Hua Ge, Di Ding, Jian-Yong Tumour Biol Research Article In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13277-014-2773-4) contains supplementary material, which is available to authorized users. Springer Netherlands 2014-12-18 /pmc/articles/PMC4375295/ /pubmed/25519684 http://dx.doi.org/10.1007/s13277-014-2773-4 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Research Article
Zhao, Guang-Yin
Lin, Zong-Wu
Lu, Chun-Lai
Gu, Jie
Yuan, Yun-Feng
Xu, Feng-Kai
Liu, Rong-Hua
Ge, Di
Ding, Jian-Yong
USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
title USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
title_full USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
title_fullStr USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
title_full_unstemmed USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
title_short USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
title_sort usp7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375295/
https://www.ncbi.nlm.nih.gov/pubmed/25519684
http://dx.doi.org/10.1007/s13277-014-2773-4
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