期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 50, 期 4, 页码 1136-1146出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2017.3904
关键词
USP20; gastric cancer; Claspin; autophagy; cell cycle; cell proliferation
类别
资金
- National Science Foundation of China [81672327, 81372645, 81502013, 81602411]
- Program of Shanghai Academic/Technology Research Leader [17XD1402600]
- FONG SHU FOOK TONG Foundation
- National Key Clinical Discipline (Oncology)
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine [20161410]
- Shanghai Municipal Commission of Health and Family Planning [20154Y496]
- SCORE Foundation [Y-MX2015-078]
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, Gl-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.
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