The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
USP7 accelerates p14ARF degradation by deubiquitinating TRIP12 and promotes HCC progression
Cai JB1, Shi GM, Dong ZR, Ke AW, Ma HH, Gao Q, Shen ZZ, Huang XY, Chen H, Yu DD, Liu LX, Zhang PF, Zhang C, Hu MY, Yang LX, Shi YH, Wang XY, Ding ZB, Qiu SJ, Sun HC, Zhou J, Shi YG, Fan J. Hepatology. 2014 Dec 29. doi: 10.1002/hep.27682. [Epub ahead of print]
Author information
1Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032, P.R. China.
Abstract
The prognosis for hepatocellular carcinoma (HCC) remains dismal in terms of overall survival (OS), and its molecular pathogenesis has not been completely defined. Here, we report that the expression of deubiquitylase USP7 is higher in human HCC tissues than in matched non-tumor tissues. Ectopic USP7 expression promotes the growth of HCC cells in vivo and in vitro. Mechanistically, USP7 overexpression fosters HCC cell growth by forming a complex with and stabilizing the TRIP12 protein, which induces constitutive p14ARF ubiquitination. Clinically, USP7 overexpression is significantly correlated with a malignant phenotype, including larger tumor size, multiple tumor, poor differentiation, elevated α-fetoprotein (AFP), and microvascular invasion. Moreover, overexpression of USP7 and/or TRIP12 correlates with shorter OS and higher cumulative recurrence rates in HCC. Together, our results reveal that USP7 stabilizes TRIP12 by deubiquitination, thus constitutively inactivating p14ARF and promoting HCC progression, and represents a novel marker for predicting prognosis and a potential therapeutic target for HCC.