The Function And Mechanism Of OTUB2 Regulating KRT80 In Gastric Cancer

Objective:OTUB2 is a deubiquitinating enzyme whose expression in gastric cancer and its prognosis and importance for patients with gastric cancer remain unclear.The search for more effective biomarkers is key to improving the outcome and prognosis of gastric cancer treatment.The aim of this study was to explore the role of OTUB2 in deubiquitination in gastric cancer and its mechanism,and to provide a new theoretical basis for the treatment and prognosis determination of gastric cancer.Methods:In this study,the expression of OTUB2 and KRT80 in cancer tissues and paired tissues of 32 pairs of gastric cancer patients was detected by Westernblot and qRT-PCR.Multi-immunofluorescence staining was used to detect the expression of OTUB2,KRT80 and Ki67 in cancer and paired tissues of 90 pairs of gastric cancer patients and the prognosis of survival of gastric cancer patients was analyzed by Kaplan-Meier and log-rank tests.Assays such as CHX and His pull-down mechanistically validated the relationship between OTUB2 and KRT80.The role of OTUB2 and KRT80 in the proliferation of gastric cancer cells was investigated by performing various in vitro and in vivo cell biological function assays and immunohistochemical methods.Results:It was found that OTUB2 is highly expressed in gastric cancer tissues and acts as an oncogene that is associated with poor prognosis in gastric cancer patients.Knockdown of OTUB2 alone inhibited the proliferative capacity of gastric cancer cell lines in vitro and in vivo,and the proliferative capacity was restored upon re-supplementation with KRT80.OTUB2 interacts directly with KRT80 and OTUB2 prolongs the half-life of KRT80.OTUB2 simultaneously deubiquitinated and protected KRT80 from proteasome-mediated degradation via Lys-48 and Lys-63 of the ubiquitin molecule,thereby stabilizing KRT80 protein expression and then activating the Akt signalling pathway via KRT80,promoting the proliferation of gastric cancer cells in vitro and in vivo.Conclusions:OTUB2 stabilizes the expression of KRT80 through deubiquitination,thereby activating the Akt signaling pathway to promote the proliferation of gastric cancer cells.Given the important role of OTUB2 in gastric cancer proliferation,we expect to develop OTUB2 as a biomarker for gastric cancer treatment or prognosis determination in the future.