Overexpression of WWP1 promotes tumorigenesis and predicts unfavorable prognosis in patients with hepatocellular carcinoma.
WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been speculated to play important roles in the development of several kinds of cancers. However, the role of WWP1 in hepatocellular carcinoma(HCC) is not clear. In the present study, we investigated the expression and prognostic role of WWP1 in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of WWP1 in HCC was also explored. We used human HCC cell lines (BEL-7402, SMMC-7721, Hep-G2, Hep-3B, SK-hep1 and Huh7) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; western blotting; immunohistochemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of WWP1. We found that WWP1 expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of WWP1 was highly correlated with poor outcome. Silencing of WWP1 expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis and cycle arrest in HCC cells. Our findings suggest that WWP1 might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker as well as a potential molecular target for the treatment of HCC.
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Xiao-Fei
XF
Zhang
Shanxi Entry-Exit Inspection and Quarantine Bureau, Shanxi 710068, People's Republic of China.
Jie
J
Chao
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Qiu-Zhong
QZ
Pan
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Ke
K
Pan
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
D-Sheng
DS
Weng
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Qi-Jing
QJ
Wang
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Jing-Jing
JJ
Zhao
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Jia
J
He
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Qing
Q
Liu
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Shan-Shan
SS
Jiang
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Chang-Long
CL
Chen
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Hong-Xia
HX
Zhang
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.|Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
Jian-Chuan
JC
Xia
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases
WWP1; hepatocellular carcinoma; oncogene; prognosis