USP27-mediated Cyclin E stabilization drives cell cycle progression and hepatocellular tumorigenesis

被引：57

作者：

Dong, Ling ^{[1
]}

Yu, Le ^{[1
]}

Bai, Chunrong ^{[1
]}

Liu, Liu ^{[1
]}

Long, Hua ^{[1
]}

Shi, Lei ^{[1
]}

Lin, Zhenghong ^{[1
]}

机构：

[1] Chongqing Univ, Sch Life Sci, Lab Pathol, Chongqing 401331, Peoples R China

来源：

ONCOGENE | 2018年 / 37卷 / 20期

基金：

中国国家自然科学基金;

关键词：

BREAST-CANCER; E OVEREXPRESSION; PROGNOSTIC-SIGNIFICANCE; S-PHASE; TRANSCRIPTIONAL ACTIVATION; LUNG-CANCER; PROTEIN; EXPRESSION; PHOSPHORYLATION; AMPLIFICATION;

D O I：

10.1038/s41388-018-0137-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Overexpression of Cyclin E has been seen in many types of cancers. However, the underlying mechanism remains enigmatic. Herein, we identified ubiquitin-specific peptidase 27 (USP27) as a Cyclin E interactor. We found that USP27 promoted Cyclin E stability by negatively regulating its ubiquitination. In addition, suppression of USP27 expression resulted in the inhibition of the growth, migration, and invasion of hepatocellular carcinoma. Furthermore, we detected a positive correlation between USP27 and Cyclin E expression in hepatocellular carcinoma tissues. Finally, we found that USP27 expression is inhibited by 5-fluorouracil (5-FU) treatment and USP27 depletion sensitizes Hep3B cells to 5-FU-induced apoptosis. USP27-mediated Cyclin E stabilization is involved in tumorigenesis, suggesting that targeting USP27 may represent a new therapeutic strategy to treat cancers with aberrant overexpression of Cyclin E protein.

引用

页码：2702 / 2713

页数：12

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