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In this study, our results showed for the first time that UBR5 was overexpressed in gallbladder cancer (GBC) tumor tissues. UBR5 overexpression was significantly associated with tumor size, histological and tumor differentiation. UBR5 overexpression was also associated with poor prognosis in patients with GBC. The knockdown of UBR5 remarkably inhibited the cell proliferation and colony formation of GBC\u2010Shandong (SD) cells in vitro and in vivo. UBR5 potentially increases the level of protein kinase B phosphorylation via the degradation of phosphatase and tensin homolog, which contributes to tumor growth in GBC. 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