USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance

Wang,Lingzhi; Chen,Tanxiu; Li,Xukun; Yan,Wei; Lou,Yanhui; Liu,Zhihua; Chen,Hongyan; Cui,Zhumei

doi:10.3892/ijo.2019.4818

USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance

Authors:
- Lingzhi Wang
- Tanxiu Chen
- Xukun Li
- Wei Yan
- Yanhui Lou
- Zhihua Liu
- Hongyan Chen
- Zhumei Cui
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Affiliations: Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266061, P.R. China, Department of Science and Education, Jiangxi Key Laboratory of Translational Cancer Research, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China, State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beiing 100021, P.R. China, 6th Department of Internal Medicine, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
Published online on: May 29, 2019 https://doi.org/10.3892/ijo.2019.4818
Pages: 277-288

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Abstract

Ubiquitin‑specific protease 39 (USP39), as one of the deubiquitinating enzymes (DUBs), exhibits aberrant an expression and has oncogenic functions in several types of cancer. However, the function and underlying molecular mechanisms of action of USP39 in ovarian cancer remain largely undetermined. The present study thus aimed to investigate whether USP39 is a promising tumor‑associated gene and whether it could be a viable target for overcoming chemotherapeutic resistance in ovarian cancer. The present study identified that USP39 was highly expressed in ovarian cancer samples with carboplatin resistance. A series of functional assays revealed that the knockdown of USP39 in ES2 and SKOV3 cells significantly decreased cell proliferation, induced cell cycle arrest at the G2/M phase and impaired the cell colony formation ability. USP39 deficiency enhanced the carboplatin‑induced apoptosis of the SKOV3 cells via the activation of poly‑ADP ribose polymerase and caspase‑3. USP39 knockdown led to the inhibition of cell migration and invasion. The opposite effects were observed when USP39 was overexpressed in the ES2 and SKOV3 cells. In vivo animal models revealed that the subcutaneous transplantation and intraperitoneal injection of USP39‑overexpressing ES2 cells increased tumor burden with or without treatment with carboplatin. However, the knockdown of USP39 suppressed SKOV3 cell growth in vivo. Mechanistic analyses also demonstrated that USP39 induced the phosphorylation of extracellular signal‑regulated kinase and AKT and increased the expression of epidermal growth factor receptor and cyclin B1. Collectively, the findings of this study suggest that USP39 may paly a vital role in regulating ovarian cancer malignant phenotypes and carboplatin resistance. Therefore, USP39 may prove to be a promising therapeutic target for patients with ovarian cancer.

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