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

作者：Dong, Ling; Yu, Le; Bai, Chunrong; Liu, Liu; Long, Hua; Shi, Lei; Lin, Zhenghong^*

来源：Oncogene, 2018, 37(20): 2702-2713.

DOI：10.1038/s41388-018-0137-z

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

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.

• 出版日期2018-5
• 单位重庆大学