Identification of the deubiquitinase USP28 as a novel molecular therapeutic target of ovarian cancer

Ubiquitin specific proteinase 28 (USP28) is a member of the deubiquitylating enzymes, which are mainly involved in cell cycle, apoptosis and DNA damage repair. Although USP28 has been found to be upre-gulated in some tumors, its role in ovarian cancer (OV) remains unclear. Here we show that USP28 was highly expressed in OV samples compared with normal ovarian tissue, and OV patients with higher USP28 levels had a worse prognosis. We found that the abnormal expression of USP28 mRNA in OV was related to the activation of I3-catenin signaling pathway, and USP28 was a transcriptional target gene of the I3-catenin/YAP1/TBX5 complex. In addition, genetic ablation or pharmacological inhibition of USP28 impaired the proliferation ability of OV cells in vitro and in vivo. In conclusion, our findings show that I3-catenin/YAP1/TBX5-mediated aberrant expression of USP28 promotes the malignant phenotype of OV, suggesting that USP28 may be a therapeutic target for OV.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Ubiquitin specific proteinase 28 (USP28) is highly expressed in ovarian cancer (OV) samples and elevated USP28 levels are associated with poor prognosis. USP28 abnormal expression is linked to the activation of the I3-catenin signaling pathway and it is a transcriptional target gene of the I3-catenin/YAP1/TBX5 complex. Genetic ablation or pharmacological inhibition of USP28 impairs the proliferation ability of OV cells. These findings suggest that USP28 may serve as a therapeutic target for ovarian cancer.