High expression of PSMC2 promotes gallbladder cancer through regulation of GNG4 and predicts poor prognosis

Gallbladder cancer (GBC) is a common malignant tumor of the biliary tract, which accounts for 80–95% of biliary tumors worldwide, and is the leading cause of biliary malignant tumor-related death. This study identified PSMC2 as a potential regulator in the development of GBC. We showed that PSMC2 expression in GBC tissues is significantly higher than that in normal tissues, while high PSMC2 expression was correlated with more advanced tumor grade and poorer prognosis. The knockdown of PSMC2 in GBC cells induced significant inhibition of cell proliferation, colony formation and cell motility, while the promotion of cell apoptosis. The construction and observation of the mice xenograft model also confirmed the inhibitory effects of PSMC2 knockdown on GBC development. Moreover, our mechanistic study recognized GNG4 as a potential downstream target of PSMC2, knockdown of which could aggravate the tumor suppression induced by PSMC2 knockdown in vitro and in vivo. In conclusion, for the first time, PSMC2 was revealed as a tumor promotor in the development of GBC, which could regulate cell phenotypes of GBC cells through the interaction with GNG4, and maybe a promising therapeutic target in GBC treatment.