Skip to main content
Top
Published in: Medical Oncology 1/2015

01-01-2015 | Original Paper

Ubiquitin-specific protease 14 (USP14) regulates cellular proliferation and apoptosis in epithelial ovarian cancer

Authors: Yingying Wang, Juan Wang, Jianxin Zhong, Yan Deng, Qinghua Xi, Song He, Shuyun Yang, Lifei Jiang, Menghui Huang, Chunhui Tang, Rong Liu

Published in: Medical Oncology | Issue 1/2015

Login to get access

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Thus, there is an emergent need to invest a novel therapeutic for EOC. In this study, we defined ubiquitin-specific protease 14 (USP14) as a therapeutic target for EOC. Western blot was used to evaluate the expression of USP14 in nine fresh EOC tissues and three fresh normal ovarian tissues. The protein level of USP14 was higher in the cancer samples compared with that in the normal ovary tissues. Immunohistochemistry analysis was performed on formalin-fixed paraffin-embedded section of 116 cases of EOCs and indicated that USP14 was significantly associated with clinical pathologic variables. Kaplan–Meier curve showed that high expression of USP14 was related to poor prognosis of EOC patients. Starvation and re-feeding assay was used to imitate cell cycle, suggesting that USP14 played a critical role in SKOV3 cell proliferation. CCK-8 assay showed that SKOV3 cells treated with USP14-shRNA (shUSP14) grew more slowly than control group. Flow cytometry revealed that the reduced expression of USP14 induced the apoptosis of the SKOV3 EOC cells. In summary, our findings suggest that USP14 is involved in the progression of EOC and that it may be a useful target of therapy in EOC.
Literature
2.
go back to reference Anuradha S, et al. Survival of Australian women with invasive epithelial ovarian cancer: a population-based study. Med J Aust. 2014;201(5):283–8.PubMedCrossRef Anuradha S, et al. Survival of Australian women with invasive epithelial ovarian cancer: a population-based study. Med J Aust. 2014;201(5):283–8.PubMedCrossRef
3.
go back to reference Mialki RK, et al. Overexpression of USP14 protease reduces I-κB protein levels and increases cytokine release in lung epithelial cells. J Biol Chem. 2013;288(22):15437–41.PubMedCentralPubMedCrossRef Mialki RK, et al. Overexpression of USP14 protease reduces I-κB protein levels and increases cytokine release in lung epithelial cells. J Biol Chem. 2013;288(22):15437–41.PubMedCentralPubMedCrossRef
5.
go back to reference Puente XS, et al. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet. 2003;4(7):544–58.PubMedCrossRef Puente XS, et al. Human and mouse proteases: a comparative genomic approach. Nat Rev Genet. 2003;4(7):544–58.PubMedCrossRef
6.
go back to reference Ishiwata S, et al. Increased expression of queuosine synthesizing enzyme, tRNA-guanine transglycosylase, and queuosine levels in tRNA of leukemic cells. J Biochem. 2001;129(1):13–7.PubMedCrossRef Ishiwata S, et al. Increased expression of queuosine synthesizing enzyme, tRNA-guanine transglycosylase, and queuosine levels in tRNA of leukemic cells. J Biochem. 2001;129(1):13–7.PubMedCrossRef
7.
go back to reference Shinji S, et al. Ubiquitin-specific protease 14 expression in colorectal cancer is associated with liver and lymph node metastases. Oncol Rep. 2006;15(3):539–43.PubMed Shinji S, et al. Ubiquitin-specific protease 14 expression in colorectal cancer is associated with liver and lymph node metastases. Oncol Rep. 2006;15(3):539–43.PubMed
8.
go back to reference Chuensumran U, et al. Ubiquitin-specific protease 14 expression associated with intrahepatic cholangiocarcinoma cell differentiation. Asian Pac J Cancer Prev. 2011;12(3):775–9.PubMed Chuensumran U, et al. Ubiquitin-specific protease 14 expression associated with intrahepatic cholangiocarcinoma cell differentiation. Asian Pac J Cancer Prev. 2011;12(3):775–9.PubMed
9.
go back to reference Wu N, et al. Over-expression of deubiquitinating enzyme USP14 in lung adenocarcinoma promotes proliferation through the accumulation of beta-catenin. Int J Mol Sci. 2013;14(6):10749–60.PubMedCentralPubMedCrossRef Wu N, et al. Over-expression of deubiquitinating enzyme USP14 in lung adenocarcinoma promotes proliferation through the accumulation of beta-catenin. Int J Mol Sci. 2013;14(6):10749–60.PubMedCentralPubMedCrossRef
10.
go back to reference Wu N, et al. MiR-4782-3p inhibited non-small cell lung cancer growth via USP14. Cell Physiol Biochem. 2014;33(2):457–67.PubMedCrossRef Wu N, et al. MiR-4782-3p inhibited non-small cell lung cancer growth via USP14. Cell Physiol Biochem. 2014;33(2):457–67.PubMedCrossRef
11.
go back to reference Yang Y, et al. Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007;23(6):504–6.PubMed Yang Y, et al. Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007;23(6):504–6.PubMed
12.
go back to reference Semaan A, et al. MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf(1)/cip(1)). Pharm Res. 2011;28(12):3079–90.PubMedCrossRef Semaan A, et al. MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf(1)/cip(1)). Pharm Res. 2011;28(12):3079–90.PubMedCrossRef
13.
go back to reference Hang Q, et al. Expression of Spy1 protein in human non-Hodgkin’s lymphomas is correlated with phosphorylation of p27Kip1 on Thr187 and cell proliferation. Med Oncol. 2012;29(5):3504–14.PubMedCrossRef Hang Q, et al. Expression of Spy1 protein in human non-Hodgkin’s lymphomas is correlated with phosphorylation of p27Kip1 on Thr187 and cell proliferation. Med Oncol. 2012;29(5):3504–14.PubMedCrossRef
14.
go back to reference Kapuria V, et al. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010;70(22):9265–76.PubMedCrossRef Kapuria V, et al. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010;70(22):9265–76.PubMedCrossRef
15.
go back to reference Kim BG, et al. Activation of caspases and inhibition of ribosome biogenesis mediate antitumor activity of Chijongdan in A549 non-small lung cancer cells. BMC Complement Altern Med. 2014;14(1):420.PubMedCentralPubMedCrossRef Kim BG, et al. Activation of caspases and inhibition of ribosome biogenesis mediate antitumor activity of Chijongdan in A549 non-small lung cancer cells. BMC Complement Altern Med. 2014;14(1):420.PubMedCentralPubMedCrossRef
17.
go back to reference CL Walters Haygood, et al. Ovarian cancer stem cells: can targeted therapy lead to improved progression-free survival? World. J Stem Cells. 2014;6(4):441–7.CrossRef CL Walters Haygood, et al. Ovarian cancer stem cells: can targeted therapy lead to improved progression-free survival? World. J Stem Cells. 2014;6(4):441–7.CrossRef
18.
go back to reference Tian Z, et al. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014;123(5):706–16.PubMedCrossRef Tian Z, et al. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014;123(5):706–16.PubMedCrossRef
20.
go back to reference Ding F, et al. The role of the ubiquitin–proteasome pathway in cancer development and treatment. Front Biosci (Landmark Ed). 2014;19:886–95.CrossRef Ding F, et al. The role of the ubiquitin–proteasome pathway in cancer development and treatment. Front Biosci (Landmark Ed). 2014;19:886–95.CrossRef
21.
go back to reference Chen D, Dou QP. The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention. Curr Protein Pept Sci. 2010;11(6):459–70.PubMedCentralPubMedCrossRef Chen D, Dou QP. The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention. Curr Protein Pept Sci. 2010;11(6):459–70.PubMedCentralPubMedCrossRef
22.
go back to reference Romano A, Conticello C, Di Raimondo F. Bortezomib for the treatment of previously untreated multiple myeloma. Immunotherapy. 2013;5(4):327–52.PubMedCrossRef Romano A, Conticello C, Di Raimondo F. Bortezomib for the treatment of previously untreated multiple myeloma. Immunotherapy. 2013;5(4):327–52.PubMedCrossRef
23.
go back to reference Takagi K, Mizushima T. Structure and functional mechanisms of proteasome dedicated chaperones. Seikagaku. 2013;85(9):789–94.PubMed Takagi K, Mizushima T. Structure and functional mechanisms of proteasome dedicated chaperones. Seikagaku. 2013;85(9):789–94.PubMed
24.
go back to reference Ernst A, et al. A strategy for modulation of enzymes in the ubiquitin system. Science. 2013;339(6119):590–5.PubMedCrossRef Ernst A, et al. A strategy for modulation of enzymes in the ubiquitin system. Science. 2013;339(6119):590–5.PubMedCrossRef
25.
go back to reference Musat M, et al. Cell cycle dysregulation in pituitary oncogenesis. Front Horm Res. 2004;32:34–62.PubMedCrossRef Musat M, et al. Cell cycle dysregulation in pituitary oncogenesis. Front Horm Res. 2004;32:34–62.PubMedCrossRef
26.
go back to reference Brnjic S, et al. Induction of tumor cell apoptosis by a proteasome deubiquitinase inhibitor is associated with oxidative stress. Antioxid Redox Signal. 2013. doi:10.1089/ars.2013.5322. Brnjic S, et al. Induction of tumor cell apoptosis by a proteasome deubiquitinase inhibitor is associated with oxidative stress. Antioxid Redox Signal. 2013. doi:10.​1089/​ars.​2013.​5322.
Metadata
Title
Ubiquitin-specific protease 14 (USP14) regulates cellular proliferation and apoptosis in epithelial ovarian cancer
Authors
Yingying Wang
Juan Wang
Jianxin Zhong
Yan Deng
Qinghua Xi
Song He
Shuyun Yang
Lifei Jiang
Menghui Huang
Chunhui Tang
Rong Liu
Publication date
01-01-2015
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0379-8

Other articles of this Issue 1/2015

Medical Oncology 1/2015 Go to the issue