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USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner

Ubiquitin-specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin-like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectop...

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Autores principales: Pan, Aonan, Li, Yue, Guan, Jian, Zhang, Pengxia, Zhang, Chunbin, Han, Yupeng, Zhang, Tao, Cheng, Yao, Sun, Luo, Lu, Shizhen, Weng, Jinru, Ren, Qiaosheng, Fan, Shengjie, Wang, Weiqun, Wang, Jingtao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025074/
https://www.ncbi.nlm.nih.gov/pubmed/33850562
http://dx.doi.org/10.3892/ol.2021.12682
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author Pan, Aonan
Li, Yue
Guan, Jian
Zhang, Pengxia
Zhang, Chunbin
Han, Yupeng
Zhang, Tao
Cheng, Yao
Sun, Luo
Lu, Shizhen
Weng, Jinru
Ren, Qiaosheng
Fan, Shengjie
Wang, Weiqun
Wang, Jingtao
author_facet Pan, Aonan
Li, Yue
Guan, Jian
Zhang, Pengxia
Zhang, Chunbin
Han, Yupeng
Zhang, Tao
Cheng, Yao
Sun, Luo
Lu, Shizhen
Weng, Jinru
Ren, Qiaosheng
Fan, Shengjie
Wang, Weiqun
Wang, Jingtao
author_sort Pan, Aonan
collection PubMed
description Ubiquitin-specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin-like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectopic expression or downregulation of USP18 expression may contribute to tumorigenesis. However, the role of USP18 in uterine cervical cancer (UCC) remains unclear. Thus, the present study aimed to investigate USP18 expression in a human tissue microarray constructed using UCC and non-cancer cervical tissues, and to determine the potential role and molecular mechanism by which USP18 is implicated in the tumor biology of human UCC HeLa cells. Microarray analysis demonstrated that USP18 protein expression was downregulated in tumor tissues compared with in normal tissues. In addition, in vitro analysis revealed that USP18-knockdown markedly promoted the proliferation, colony formation, migration and aggressiveness of HeLa cells. Mechanistic analysis demonstrated that USP18-knockdown increased the levels of Bcl-2, STAT3 and phosphorylated-ERK in HeLa cells. Notably, USP18 silencing-induced malignant phenotypes were interrupted following exogenous administration of the ERK1/2 inhibitor PD98059. Overall, the results of the present study suggested that USP18 may be a potent inhibitor involved in UCC tumor-associated biological behaviors, which are associated with the ERK signaling pathway.
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spelling pubmed-80250742021-04-12 USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner Pan, Aonan Li, Yue Guan, Jian Zhang, Pengxia Zhang, Chunbin Han, Yupeng Zhang, Tao Cheng, Yao Sun, Luo Lu, Shizhen Weng, Jinru Ren, Qiaosheng Fan, Shengjie Wang, Weiqun Wang, Jingtao Oncol Lett Articles Ubiquitin-specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin-like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectopic expression or downregulation of USP18 expression may contribute to tumorigenesis. However, the role of USP18 in uterine cervical cancer (UCC) remains unclear. Thus, the present study aimed to investigate USP18 expression in a human tissue microarray constructed using UCC and non-cancer cervical tissues, and to determine the potential role and molecular mechanism by which USP18 is implicated in the tumor biology of human UCC HeLa cells. Microarray analysis demonstrated that USP18 protein expression was downregulated in tumor tissues compared with in normal tissues. In addition, in vitro analysis revealed that USP18-knockdown markedly promoted the proliferation, colony formation, migration and aggressiveness of HeLa cells. Mechanistic analysis demonstrated that USP18-knockdown increased the levels of Bcl-2, STAT3 and phosphorylated-ERK in HeLa cells. Notably, USP18 silencing-induced malignant phenotypes were interrupted following exogenous administration of the ERK1/2 inhibitor PD98059. Overall, the results of the present study suggested that USP18 may be a potent inhibitor involved in UCC tumor-associated biological behaviors, which are associated with the ERK signaling pathway. D.A. Spandidos 2021-05 2021-03-29 /pmc/articles/PMC8025074/ /pubmed/33850562 http://dx.doi.org/10.3892/ol.2021.12682 Text en Copyright: © Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Pan, Aonan
Li, Yue
Guan, Jian
Zhang, Pengxia
Zhang, Chunbin
Han, Yupeng
Zhang, Tao
Cheng, Yao
Sun, Luo
Lu, Shizhen
Weng, Jinru
Ren, Qiaosheng
Fan, Shengjie
Wang, Weiqun
Wang, Jingtao
USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner
title USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner
title_full USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner
title_fullStr USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner
title_full_unstemmed USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner
title_short USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner
title_sort usp18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an erk signal-dependent manner
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025074/
https://www.ncbi.nlm.nih.gov/pubmed/33850562
http://dx.doi.org/10.3892/ol.2021.12682
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