ObjectiveTo investigate the role of ovarian tumor (OTU) domain protein 6B (OTUD6B) in the progression of gastric cancer (GC) and to clarify its related molecular mechanism.MethodsThe differential expression of OTUD6B was analyzed by TIMER 2.0 database. Western blotting and qRT-PCR were used to analyze the expression differences of OTUD6B in gastric cancer tissues and cell lines, and Kaplan-Meier was used to analyze the correlation between OTUD6B expression and prognosis of patients with gastric cancer. The expression of OTUD6B in gastric cancer and adjacent tissues was further detected by immunohistochemistry (IHC). The expression of OTUD6B in HGC-27 and AGS cells was knocked down by lentivirus-mediated gene silencing technique. The effects of OTUD6B on the proliferation of gastric cancer cells were evaluated by CCK-8 and EDU experiments. The effect of OTUD6B on the migration ability of gastric cancer cells was investigated by transwell and scratch tests. The interaction between OTUD6B and the target was verified by co-immunoprecipitation and immunofluorescence techniques.ResultsOTUD6B expression was significantly up-regulated in gastric cancer tissues, and high expression of OTUD6B was associated with poor overall survival. In vitro experiments showed that the proliferation and migration ability of gastric cancer cells were significantly weakened after OTUD6B knockdown. Mechanically, OTUD6B binded and deubiquitinated poly A binding protein cytoplasmic 1 (PABPC1), reducing the level of K48 ubiquitination modification and finally stabilizing PABPC1. The response experiment showed that overexpression of PABPC1 partially reversed the knockdown effect of OTUD6B.ConclusionOTUD6B can stabilize PABPC1 through binding and deubiquitination, and promote the proliferation and migration of gastric cancer cells, suggesting that OTUD6B may be a potential therapeutic target for the progression of gastric cancer.