Ubiquitin-specific protease 4 inhibits breast cancer cell growth through the upregulation of PDCD4

被引:43
作者
Li, Yang [1 ]
Jiang, Daqing [1 ]
Zhang, Qi [1 ]
Liu, Xiaoli [2 ]
Cai, Zhengang [3 ]
机构
[1] Liaoning Canc Hosp & Inst, Dept Breast Surg, Shenyang 110042, Liaoning, Peoples R China
[2] Dalian Med Univ, Dept Intervent Radiol, Affiliated Hosp 2, 467 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China
[3] Dalian Med Univ, Affiliated Hosp 1, Dept Breast Surg, 222 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China
关键词
ubiquitin-specific protease 4; programmed cell death 4; breast cancer; proliferation; USP4; EXPRESSION; METASTASIS; DEUBIQUITINATION; TUMORIGENESIS; STATISTICS; PROGNOSIS; LEVEL; CUL4A; P53;
D O I
10.3892/ijmm.2016.2685
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Breast cancer is a common malignant tumor affecting women. The study of the association between breast cancer and molecular aberrations may lead to the development of novel diagnostic and therapeutic strategies for the disease. In the present study, we examined the role of ubiquitin-specific protease 4 (USP4) in breast cancer. We found that USP4 expression was significantly decreased in breast cancer tissue samples compared with paired normal breast tissue samples (P<0.001). USP4 was identified as a tumor suppressor. In addition, by inducing USP4 overexpression (using a USP4 overexpression plasmid) or the knockdown of USP4 (by transfection with a USP4 shRNA plasmid), we found that USP4 inhibited cell proliferation in vitro. We also found that USP4 suppressed tumor growth by using a mouse tumor xenograft model. Moreover, programmed cell death 4 (PCD4) was identified to be a target of USP4, which plays a role as a tumor suppressor. As a whole, our findings sugggest that USP4 acts as a tumor suppressor in breast cancer and that it may be an effective target for the treatment of breast cancer.
引用
收藏
页码:803 / 811
页数:9
相关论文
共 31 条
[1]   Pdcd4, a colon cancer prognostic that is regulated by a microRNA [J].
Allgayer, Heike .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2010, 73 (03) :185-191
[2]  
Byler S, 2014, ANTICANCER RES, V34, P1071
[3]   Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer [J].
Chen, Zhike ;
Yuan, Yate-Ching ;
Wang, Yuanzhong ;
Liu, Zheng ;
Chan, Hei Jason ;
Chen, Shiuan .
BREAST CANCER RESEARCH AND TREATMENT, 2015, 152 (01) :29-39
[4]   USP4 targets TAK1 to downregulate TNFα-induced NF-κB activation [J].
Fan, Y-H ;
Yu, Y. ;
Mao, R-F ;
Tan, X-J ;
Xu, G-F ;
Zhang, H. ;
Lu, X-B ;
Fu, S-B ;
Yang, J. .
CELL DEATH AND DIFFERENTIATION, 2011, 18 (10) :1547-1560
[5]   Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma [J].
Fischer, Nicolas ;
Goeke, Friederike ;
Splittstoesser, Vera ;
Lankat-Buttgereit, Brigitte ;
Mueller, Stefan C. ;
Ellinger, Joerg .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 417 (01) :29-34
[6]   The human UNP locus at 3p21.31 encodes two tissue-selective, cytoplasmic isoforms with deubiquitinating activity that have reduced expression in small cell lung carcinoma cell lines [J].
Frederick, A ;
Rolfe, M ;
Chiu, MI .
ONCOGENE, 1998, 16 (02) :153-165
[7]   High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: Inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers [J].
Fredersdorf, S ;
Burns, J ;
Milne, AM ;
Packham, G ;
Fallis, L ;
Gillett, CE ;
Royds, JA ;
Peston, D ;
Hall, PA ;
Hanby, AM ;
Barnes, DM ;
Shousha, S ;
OHare, MJ ;
Lu, X .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (12) :6380-6385
[8]   Breast cancer stem cells: Multiple capacities in tumor metastasis [J].
Geng, Shao-Qing ;
Alexandrou, Aris T. ;
Li, Jian Jian .
CANCER LETTERS, 2014, 349 (01) :1-7
[9]   Ubiquitin-specific protease 4 promotes TNF-α-induced apoptosis by deubiquitination of RIP1 in head and neck squamous cell carcinoma [J].
Hou, Xiaozhi ;
Wang, Lijuan ;
Zhang, Lei ;
Pan, Xinliang ;
Zhao, Wei .
FEBS LETTERS, 2013, 587 (04) :311-316
[10]   RETRACTED: Ubiquitin-specific protease 4 is inhibited by its ubiquitin-like domain (Retracted article. See vol. 15, pg. 121, 2014) [J].
Luna-Vargas, Mark P. A. ;
Faesen, Alex C. ;
van Dijk, Willem J. ;
Rape, Michael ;
Fish, Alexander ;
Sixma, Titia K. .
EMBO REPORTS, 2011, 12 (04) :365-372