title: Knockdown of WWP1 inhibits growth and induces apoptosis in hepatoma carcinoma cells through the activation of caspase3 and p53.
abstract: The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). The human WW domain containing E3 ubiquitin protein ligase 1 (WWP1) gene is frequently amplified in prostate and breast cancers, however, its role in cancer has not yet been extensively studied. Especially, the role of WWP1 in HCC has not yet been studied. Firstly, we analyzed the expression of WWP1 in HCC samples. We found that protein levels of WWP1 are higher in most HCC cancerous tissues as compared with their matched adjacent non-tumor tissues. Additionally, the WWP1 mRNA was also amplified in all 7 HCC tissues. Knockdown of the endogenous WWP1 using small interfering RNA further showed that deficiency of WWP1 suppressed cell growth and caused apoptosis in HCC cells. Knocking down WWP1 promoted cleaved caspase3 protein and p53 expression in HCC cells, and caspase3 inhibition could prevent cell apoptosis induced by the knockdown of WWP1. All together these results indicate that protein levels of WWP1 in most HCC tissues are higher than non-tumor tissues, and knockdown of WWP1 inhibits growth and induces apoptosis in HCC cells through the activation of caspase3 and p53. Therefore, WWP1 gene might be a potential molecular target of HCC.
authors.affiliation: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China. Electronic address: chengqian@bjmu.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China. Electronic address: caocaoxiao@163.com.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China. Electronic address: yuanfuwen@pku.edu.cn.
authors.forename: Fuwen
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China. Electronic address: liguodong1977@bjmu.edu.cn.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China. Electronic address: ttj@bjmu.edu.cn.
authors.forename: Tanjun
authors.initials: T
authors.lastname: Tong
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; Caspase3; Growth; HCC; WWP1; p53