The activation of the Notch signaling pathway by UBE2C promotes the proliferation and metastasis of hepatocellular carcinoma

被引:1
作者
Zhan, Ping [1 ]
Lu, Yuyan [1 ]
Lu, Jing [1 ]
Cheng, Yizhe [1 ]
Luo, Changhong [1 ]
Yang, Fan [1 ]
Xi, Wenqing [2 ]
Wang, Jinzhu [2 ,3 ]
Cen, Xuesong [1 ]
Wang, Fuqiang [2 ]
Xie, Chengrong [1 ]
Yin, Zhenyu [2 ]
机构
[1] Xiamen Univ, Zhongshan Hosp, Sch Med,Fujian Prov Key Lab Chron Liver Dis & Hepa, Xiamen Translat Med Key Lab Digest Syst Tumor, 209 South Hubin Rd, Xiamen 361004, Fujian, Peoples R China
[2] Beijing Univ Chinese Med, Xiamen Hosp Tradit Chinese Med, Dept Hepatobiliary Surg, Xiamen Key Lab Liver Dis, 1739 Xianyue Rd, Xiamen 361001, Fujian, Peoples R China
[3] Fujian Univ Tradit Chinese Med, Coll Integrat Med, Fuzhou 350122, Fujian, Peoples R China
来源
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
基金
中国国家自然科学基金;
关键词
EMT; Ubiquitination; Notch signaling; GROWTH; CANCER; OVEREXPRESSION; BINDING; CELLS;
D O I
10.1038/s41598-024-72714-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
UBE2C, a ubiquitin-conjugating enzyme, functions as an oncogene in different types of human cancers. Nonetheless, the exact influence of UBE2C on the development of HCC via regulation of ubiquitination remains uncertain. Here, we found that UBE2C displayed elevated levels of expression in HCC and was associated with an unfavorable prognosis, as evidenced by the analysis of the TCGA database and the examination of clinical specimens. The role of UBE2C in HCC revealed its ability to promote the growth and metastasis of HCC. Mechanistically, UBE2C activated Notch signaling, as evidenced by the upregulation of N1ICD and Hes1, crucial components of the Notch pathway, and activation of the RBP-JK luciferase reporter by UBE2C. Finally, rescue experiments demonstrated that the oncogenic role of UBE2C was eliminated through treatment with the Notch inhibitor DAPT, while overexpression of N1ICD alleviated the anticarcinogenic impact of knockdown of UBE2C. Altogether, the results of our study indicate that UBE2C plays a role in the activation of Notch signaling and could potentially serve as a viable target for therapeutic interventions in HCC.
引用
收藏
页数:15
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