Overexpression of SPAG9 correlates with poor prognosis and tumor progression in hepatocellular carcinoma

被引:25
作者
Xie, Chengyao [1 ,2 ]
Fu, Lin [1 ,2 ]
Liu, Nan [1 ,2 ]
Li, Qingchang [1 ,2 ]
机构
[1] China Med Univ, Dept Pathol, Affiliated Hosp 1, Shenyang 110001, Liaoning, Peoples R China
[2] China Med Univ, Coll Basic Med Sci, Shenyang 110001, Liaoning, Peoples R China
关键词
Hepatocellular carcinoma; SPAG9; Cyclin D1; LEUCINE-ZIPPER PROTEIN; CYCLIN D1; ANTIGEN; 9; SCAFFOLDING PROTEIN; CELL; JLP; SENESCENCE; MIGRATION; BIOMARKER; STRATEGY;
D O I
10.1007/s13277-014-2030-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Sperm-associated antigen 9 (SPAG9) was reported as a novel biomarker for several cancers and associated with the malignant behavior of cancer cells. However, its expression pattern and biological role in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed SPAG9 expression in human HCC tissues by immunohistochemistry and found that SPAG9 overexpression is correlated with tumor stage (p < 0.001), tumor multiplicity (p = 0.019), tumor size (p = 0.034), AFP levels (p = 0.006), and tumor relapse (p = 0.0017). Furthermore, SPAG9 overexpression is correlated with poor overall survival (p < 0.001) and relapse-free survival (p = 0.002). Transfection of SPAG9 small interfering RNA (siRNA) was performed in Bel-7402 cell line. Colony formation and MTT showed that SPAG9 siRNA knockdown inhibited HCC cell proliferation. We also found that SPAG9 depletion could increase cell apoptosis. In addition, the level of cyclin D1 and cyclin E protein expression was downregulated after siRNA treatment. In conclusion, SPAG9 is overexpressed in human HCC and serves as a prognostic marker. SPAG9 contributes to cancer cell growth through regulation of cyclin proteins.
引用
收藏
页码:7685 / 7691
页数:7
相关论文
共 30 条
[1]   N-cadherin Regulates p38 MAPK Signaling via Association with JNK-associated Leucine Zipper Protein IMPLICATIONS FOR NEURODEGENERATION IN ALZHEIMER DISEASE [J].
Ando, Koichi ;
Uemura, Kengo ;
Kuzuya, Akira ;
Maesako, Masato ;
Asada-Utsugi, Megumi ;
Kubota, Masakazu ;
Aoyagi, Nobuhisa ;
Yoshioka, Katsuji ;
Okawa, Katsuya ;
Inoue, Haruhisa ;
Kawamata, Jun ;
Shimohama, Shun ;
Arai, Tetsuaki ;
Takahashi, Ryosuke ;
Kinoshita, Ayae .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (09) :7619-7628
[2]  
Deane NG, 2001, CANCER RES, V61, P5389
[3]   The Scaffold Protein c-Jun NH2-Terminal Kinase-associated Leucine Zipper Protein Regulates Cell Migration through Interaction with the G Protein G13 [J].
Gantulga, Davaakhuu ;
Tuvshintugs, Baljinnyam ;
Endo, Yoshio ;
Takino, Takahisa ;
Sato, Hiroshi ;
Murakami, Seishi ;
Yoshioka, Katsuji .
JOURNAL OF BIOCHEMISTRY, 2008, 144 (06) :693-700
[4]   Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma [J].
Garg, Manoj ;
Kanojia, Deepika ;
Khosla, Aashima ;
Dudha, Namrata ;
Sati, Satish ;
Chaurasiya, Dipak ;
Jagadish, Nirmala ;
Seth, Amlesh ;
Kumar, Rajive ;
Gupta, Samir ;
Gupta, Anju ;
Lohiya, Nirmal Kumar ;
Suri, Anil .
CANCER RESEARCH, 2008, 68 (20) :8240-8248
[5]   Small Interfering RNA-Mediated Down-Regulation of SPAG9 Inhibits Cervical Tumor Growth [J].
Garg, Manoj ;
Kanojia, Deepika ;
Suri, Sushma ;
Suri, Anil .
CANCER, 2009, 115 (24) :5688-5699
[6]   Sperm-associated Antigen 9 Is a Biomarker for Early Cervical Carcinoma [J].
Garg, Manoj ;
Kanojia, Deepika ;
Salhan, Sudha ;
Suri, Sushma ;
Gupta, Anju ;
Lohiya, Nirmal Kumar ;
Suri, Anil .
CANCER, 2009, 115 (12) :2671-2683
[7]   JNK-mediated Phosphorylation of Cdc25C Regulates Cell Cycle Entry and G2/M DNA Damage Checkpoint [J].
Gutierrez, Gustavo J. ;
Tsuji, Toshiya ;
Cross, Janet V. ;
Davis, Roger J. ;
Templeton, Dennis J. ;
Jiang, Wei ;
Ronai, Ze'ev A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (19) :14217-14228
[8]   Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein [J].
Jagadish, N ;
Rana, R ;
Selvi, R ;
Mishra, D ;
Garg, M ;
Yadav, S ;
Herr, JC ;
Okumura, K ;
Hasegawa, A ;
Koyama, K ;
Suri, A .
BIOCHEMICAL JOURNAL, 2005, 389 :73-82
[9]   Sperm-Associated Antigen 9, a Novel Biomarker for Early Detection of Breast Cancer [J].
Kanojia, Deepika ;
Garg, Manoj ;
Gupta, Samir ;
Gupta, Anju ;
Suri, Anil .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2009, 18 (02) :630-639
[10]   JNK-interacting leucine zipper protein is a novel scaffolding protein in the gala signaling pathway [J].
Kashef, K ;
Lee, CM ;
Ha, JH ;
Reddy, EP ;
Dhanasekaran, DN .
BIOCHEMISTRY, 2005, 44 (43) :14090-14096