title: Deubiquitinating enzyme USP20 is a positive regulator of Claspin and suppresses the malignant characteristics of gastric cancer cells.
abstract: The aim of the present study was to investigate the clinical significance, the biological function and the mechanisms of USP20 in gastric cancer. The expression of USP20 in 89 pairs of primary gastric cancer and peritumoral gastric tissues specimens were measured by immunohistochemistry. The correlation of USP20 expression with the survival and the clinicopathological characteristics of patients were analyzed. Moreover, the underlying mechanisms of ectopic USP20 expression and its impact on GC cells were also investigated. We found that the expression of USP20 is relatively low in GC tissues and negatively correlated with tumor size, tumor invasion and TNM staging. High expression of USP20 in GC predicted longer survival. Experimentally, small interfering RNA-mediated knockdown of USP20 expression significantly promoted cell proliferation, accelerated G1-S phase transition and attenuated the autophagy activity. Overexpression of USP20 led to the inhibition of proliferation, G1-S cell cycle transition delay and autophagy activation. Mechanistically, we confirmed that silencing the expression of USP20 in GC cells could reduce Claspin protein levels without altering Claspin mRNA levels, which is involved in the antitumor activity of USP20. Furthermore, the expression level of Claspin was relatively higher in peritumoral tissue than that of GC tissues and higher expression of Claspin in GC was also correlated with good prognosis of patients. Given its pivotal role in gastric tumorigenesis and progression, USP20 functioned as the tumor suppressor in GC and possessed promising value to be a therapeutic target for GC.
authors.affiliation: Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang