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.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Institute of Orthopaedics, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Fengqing
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China. Electronic address: drnail@sina.com.
authors.forename: Fangbao
authors.initials: F
authors.lastname: Ding
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D009857:Oncogenes; D055550:Protein Stability; D013379:Substrate Specificity; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D043222:Ubiquitin Thiolesterase
chemical_list: D051546:Cyclooxygenase 2; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human
keywords: Cyclooxygenase-2; Deubiquitination; Non-small cell lung cancer; Prostaglandin E2; Ubiquitin-specific protease 22