UBE2M promotes cell proliferation via the β-catenin/cyclin D1 signaling in hepatocellular carcinoma

被引:21
作者
Zhang, Guang-Cong [1 ,2 ,3 ]
Yu, Xiang-Nan [2 ,3 ]
Sun, Jia-Lei [2 ,3 ]
Xiong, Ju [4 ]
Yang, Yi-Jun [5 ]
Jiang, Xue-Mei [1 ,5 ,6 ]
Zhu, Ji-Min [2 ,3 ]
机构
[1] Cent South Univ, Xiangya Sch Med, Affiliated Haikou Hosp, Dept Gastroenterol, Haikou 570100, Hainan, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Dept Gastroenterol & Hepatol, Shanghai 200030, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Shanghai Inst Liver Dis, Shanghai 200030, Peoples R China
[4] Hainan Gen Hosp, Dept Hepatobiliary Surg, Haikou 570100, Hainan, Peoples R China
[5] Cent South Univ, Xiangya Sch Med, Affiliated Haikou Hosp, Dept Hepatobiliary Surg, Haikou 570100, Hainan, Peoples R China
[6] Hainan Gen Hosp, Dept Gastroenterol, Haikou 570100, Hainan, Peoples R China
来源
AGING-US | 2020年 / 12卷 / 03期
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; ubiquitin-conjugating enzyme E2M; prognosis; beta-catenin; proliferation; WNT/BETA-CATENIN; RADIOFREQUENCY ABLATION; PATHWAY; TARGET; CANCER; EXPRESSION; ROLES;
D O I
10.18632/aging.102749
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Upregulated ubiquitin-conjugating enzyme E2M (UBE2M) is associated with poor prognosis in malignancies; However, the phenotype and mechanism of action of UBE2M in hepatocellular carcinoma (HCC) remain elusive. Here, we report that UBE2M is overexpressed and correlated with poor prognosis in HCC patients. The UBE2M level is an independent prognostic factor for HCC patients. UBE2M knockdown inhibits HCC cell proliferation, migration, and invasion, whereas its overexpression has an opposite effect. Mechanistically, upregulated UBE2M exerts oncogenic effects by translocation of accumulated beta-catenin from the cytoplasm to the nucleus, thus activating downstream beta-catenin/cyclin D1 signaling. In summary, our study demonstrates a notable role of UBE2M in promoting the growth of HCC, providing a novel strategy for HCC prevention and treatment.
引用
收藏
页码:2373 / 2392
页数:20
相关论文
共 42 条
[1]   The Restriction Point of the Cell Cycle [J].
Blagosklonny, Mikhail V. ;
Pardee, Arthur B. .
CELL CYCLE, 2002, 1 (02) :103-110
[2]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[3]   Neddylation Promotes Ubiquitylation and Release of Ku from DNA-Damage Sites [J].
Brown, Jessica S. ;
Lukashchuk, Natalia ;
Sczaniecka-Clift, Matylda ;
Britton, Sebastien ;
le Sage, Carlos ;
Calsou, Patrick ;
Beli, Petra ;
Galanty, Yaron ;
Jackson, Stephen P. .
CELL REPORTS, 2015, 11 (05) :704-714
[4]   MicroRNA-551b-3p inhibits tumour growth of human cholangiocarcinoma by targeting Cyclin D1 [J].
Chang, Weiping ;
Wang, Yuan ;
Li, WenZhi ;
Shi, Lei ;
Geng, Zhimin .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2019, 23 (08) :4945-4954
[5]   Wnt/β-catenin signaling in development and disease [J].
Clevers, Hans .
CELL, 2006, 127 (03) :469-480
[6]   Wnt/β-Catenin Signaling and Disease [J].
Clevers, Hans ;
Nusse, Roel .
CELL, 2012, 149 (06) :1192-1205
[7]   Inactivating UBE2M Impacts the DNA Damage Response and Genome Integrity Involving Multiple Cullin Ligases [J].
Cukras, Scott ;
Morffy, Nicholas ;
Ohn, Takbum ;
Kee, Younghoon .
PLOS ONE, 2014, 9 (07)
[8]   The Wnt/β-catenin pathway as a therapeutic target in human hepatocellular carcinoma [J].
Dahmani, Rajae ;
Just, Pierre-Alexandre ;
Perret, Christine .
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, 2011, 35 (11) :709-713
[9]   CIP2A mediates fibronectin-induced bladder cancer cell proliferation by stabilizing β-catenin [J].
Gao, Fengbin ;
Xu, Tianyuan ;
Wang, Xianjin ;
Zhong, Shan ;
Chen, Shanwen ;
Zhang, Minguang ;
Zhang, Xiaohua ;
Shen, Yifan ;
Wang, Xiaojing ;
Xu, Chen ;
Shen, Zhoujun .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2017, 36
[10]   Neddylation pathway is up-regulated in human intrahepatic cholangiocarcinoma and serves as a potential therapeutic target [J].
Gao, Qiang ;
Yu, Guang-Yang ;
Shi, Jie-Yi ;
Li, Li-Hui ;
Zhang, Wen-Juan ;
Wang, Zhi-Chao ;
Yang, Liu-Xiao ;
Duan, Meng ;
Zhao, Hu ;
Wang, Xiao-Ying ;
Zhou, Jian ;
Qiu, Shuang-Jian ;
Jeong, Lak Shin ;
Jia, Li-Jun ;
Fan, Jia .
ONCOTARGET, 2014, 5 (17) :7820-7832