USP11 deubiquitinates YBX1 to promote the proliferation and metastasis of gastric cancer

CHENG Xin; GUO Xin; CHEN Yong

doi:10.13276/j.issn.2097-1656.2026.04.015

Abstract：Objective To explore the expression differences of ubiquitin-specific protease 11(USP11)in gastric cancer(GC)tissues and paired adjacent non-cancerous tissues,as well as its effects on the malignant characteristics of GC cells and underlying mechanisms.Methods Immunohistochemical staining was used to detect the expression differences of USP11 in 5 pairs of GC tissues and paired adjacent non-cancerous tissues.The relationship between USP11 expression and the prognosis of GC was retrieved from public databases.Lentiviruses were used to establish stable GC cell lines with USP11 knockdown.CCK-8 assay,colony formation assay,and EdU assay were conducted to examine the effect of USP11 knockdown on the proliferation ability of GC cells.Wound healing assay and Transwell assay were performed to evaluate the impact of USP11 knockdown on the migration and invasion abilities of GC cells.Immunoprecipitation and proteomic analysis were carried out to further identify the downstream molecules that interact with USP11.Results Immunohistochemical staining showed that the expression level of USP11 in GC tissues was significantly higher than that in paired adjacent non-cancerous tissues(P<0.01).Results from public databases indicated that high expression of USP11 was highly correlated with poor prognosis in GC patients(P<0.05).Cell experiments further demonstrated that USP11 knockdown could significantly attenuate the proliferation,migration,and invasion abilities of GC cells(P<0.01).Immunoprecipitation and proteomic analysis identified Y-box binding protein 1(YBX1)as a downstream molecule of USP11.Conclusion USP11 binds and stabilizes YBX1 through deubiquitination,thereby promoting the proliferation and migration of GC cells.