Research Paper Volume 11, Issue 21 pp 9778—9793
Ubiquitin specific peptidase 5 promotes ovarian cancer cell proliferation through deubiquitinating HDAC2
- 1 Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, P. R. China
- 2 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, P. R. China
- 3 Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P. R. China
- 4 Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, P. R. China
- 5 Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China
Received: August 6, 2019 Accepted: October 28, 2019 Published: November 13, 2019
https://doi.org/10.18632/aging.102425How to Cite
Copyright © 2019 Du et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Globally, epithelial ovarian cancer (EOC) is the most common gynecological malignancy with poor prognosis. The expression and oncogenic roles of ubiquitin specific peptidase 5 (USP5) have been reported in several cancers except EOC. In the current study, USP5 amplification was highly prevalent in patients with EOC and associated with higher mRNA expression of USP5. USP5 amplification and overexpression was positively correlated with poor prognosis of patients of ovarian serous carcinomas. Disruption of USP5 profoundly repressed cell proliferation by inducing cell cycle G0/G1 phase arrest in ovarian cancer cells. Additionally, USP5 knockdown inhibited xenograft growth in nude mice. Knockdown of USP5 decreased histone deacetylase 2 (HDAC2) expression and increased p27 (an important cell cycle inhibitor) expression in vitro and in vivo. The promoting effects of USP5 overexpression on cell proliferation and cell cycle transition, as well as the inhibitory effects of USP5 overexpression on p27 expression were mediated by HDAC2. Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2. HDAC2 protein was positively correlated USP5 protein, and negatively correlated with p27 protein in ovarian serous carcinomas tissues. Collectively, our data suggest the oncogenic function of USP5 and the potential regulatory mechanisms in ovarian carcinogenesis.