Although gastric cancer (GC) is one of the most common cancers, knowledge of its development and carcinogenesis is limited. To date, expression of ubiquitin-specific protease 3 (USP3) in all types of cancer, including GC, is still unknown. The present study explored the involvement of USP3 in the carcinogenesis and prognosis of GC. We measured USP3 expression in normal and GC tissues and cell lines. Correlations between USP3 protein level and clinicopathological parameters, as well as the significance of USP3 protein level for disease-free survival were assessed. Small hairpin RNA technology and transfection were used to investigate the effect of USP3 manipulation on cell proliferation and spreading. Moreover, xenograft proliferation and metastasis were used to explore the influence of USP3 on tumor growth and metastasis in animals. An increase in USP3 expression was observed in GC cells and tissues. The overexpression of USP3 was significantly correlated with several clinicopathological parameters and poor disease-free survival. Multivariate Cox regression analysis showed that the overexpression of USP3 was an independent prognostic biomarker. Silencing of USP3 suppressed GC cell proliferation and spreading in vitro as well as xenograft proliferation and metastasis in vivo; however, opposite results were obtained when USP3 was overexpressed. Further studies showed that USP3 influenced cell proliferation and spreading by regulating the cell cycle control- and epithelial-mesenchymal transition-related molecules. This study suggests that USP3 overexpression can be a useful biomarker for predicting the outcomes of GC patients and that USP3 targeting represents a potential modality for treating GC.
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