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Title: USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer

Abstract

The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2. - Highlights: • USP22 interacts with COX-2. • USP22 deubiquitinates and stabilizes COX-2. • USP22 is required for COX-2-mediated upregulation of prostaglandin E2.

Authors:
 [1];  [2]; ; ; ;  [1];  [1]
  1. Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092 (China)
  2. Institute of Orthopaedics, Chinese PLA General Hospital, Beijing 100853 (China)
Publication Date:
OSTI Identifier:
22462039
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 460; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CELL PROLIFERATION; HALF-LIFE; LUNGS; MODULATION; ONCOGENES; PROSTAGLANDINS; STABILITY; SUBSTRATES

Citation Formats

Xiao, Haibo, Tian, Yue, Yang, Yang, Hu, Fengqing, Xie, Xiao, Mei, Ju, and Ding, Fangbao, E-mail: drnail@sina.com. USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.03.093.
Xiao, Haibo, Tian, Yue, Yang, Yang, Hu, Fengqing, Xie, Xiao, Mei, Ju, & Ding, Fangbao, E-mail: drnail@sina.com. USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer. United States. doi:10.1016/J.BBRC.2015.03.093.
Xiao, Haibo, Tian, Yue, Yang, Yang, Hu, Fengqing, Xie, Xiao, Mei, Ju, and Ding, Fangbao, E-mail: drnail@sina.com. Fri . "USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer". United States. doi:10.1016/J.BBRC.2015.03.093.
@article{osti_22462039,
title = {USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer},
author = {Xiao, Haibo and Tian, Yue and Yang, Yang and Hu, Fengqing and Xie, Xiao and Mei, Ju and Ding, Fangbao, E-mail: drnail@sina.com},
abstractNote = {The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2. - Highlights: • USP22 interacts with COX-2. • USP22 deubiquitinates and stabilizes COX-2. • USP22 is required for COX-2-mediated upregulation of prostaglandin E2.},
doi = {10.1016/J.BBRC.2015.03.093},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 460,
place = {United States},
year = {2015},
month = {5}
}