Zhu Dawei, Gu Xing, Lin Zhengyu, Yu Dandan, Wang Jing
Department of Gynaecology and Obstetrics, Daping Hospital, Army Medical University, Chongqing, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Oncogenesis. 2021 May 20;10(5):43. doi: 10.1038/s41389-021-00330-1.
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.
胆囊癌（GBC）是一种常见的胆道恶性肿瘤，占全球胆道肿瘤的80-95%，是胆道恶性肿瘤相关死亡的主要原因。本研究确定PSMC2是GBC发生发展中的一个潜在调节因子。我们发现，GBC组织中PSMC2的表达显著高于正常组织，而PSMC2高表达与更高级别的肿瘤分级和更差的预后相关。敲低GBC细胞中的PSMC2可显著抑制细胞增殖、集落形成和细胞运动，同时促进细胞凋亡。小鼠异种移植模型的构建和观察也证实了敲低PSMC2对GBC发展的抑制作用。此外，我们的机制研究发现GNG4是PSMC2的一个潜在下游靶点，敲低该靶点可在体外和体内加重PSMC2敲低诱导的肿瘤抑制作用。总之，首次揭示PSMC2是GBC发生发展中的肿瘤促进因子，它可通过与GNG4相互作用调节GBC细胞的表型，可能是GBC治疗中有前景的治疗靶点。
