期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 493, 期 1, 页码 20-27出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.09.091
关键词
UBE2T; p53; miR-543; Hepatocellular carcinoma
资金
- National Natural Science Foundation of Guangdong [2015A030310409]
- Science and Technology Innovation Foundation of Shenzhen [JCYJ20150403101028198]
- National Natural Science Foundation of China [81402041]
Deregulation of Ubiquitin-conjugating enzyme E2T (UBE2T) contributes to the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unclear. Here, we show that UBE2T is up-regulated in HCC and exerts oncogenic activities via ubiquitination of p53. High UBE2T expression was correlated with higher pathological grade, advanced TNM stage, tumor vascular invasion, and poor overall and disease-free survivals in two independent cohorts containing 827 patients with HCC. UBE2T was further identified as an independent factor for overall survival by multivariate analyses. Luciferase reporter assays confirmed that UBE2T was directly targeted by miR-543 which was down-regulated in HCC. In vitro experiments demonstrated that UBE2T overexpression promoted, whereas UBE2T knockdown inhibited HCC cell growth. Ectopic expression of UBE2T resulted in the decreases of p53, p21 and Noxa. Further studies revealed that UBE2T facilitated the degradation of p53 protein via enhancing its ubiquitination. Collectively, our findings suggest UBE2T serves as a promising prognostic factor for HCC and functions as an oncogene. The newly identified miR-543/UBE2T/ p53 axis may represent a new potential therapeutic target for HCC intervention. (C) 2017 Elsevier Inc. All rights reserved.
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