title: Nucleostemin Knockdown Sensitizes Hepatocellular Carcinoma Cells to Ultraviolet and Serum Starvation-Induced Apoptosis.
abstract: Nucleostemin (NS) is a GTP-binding protein that is predominantly expressed in embryonic and adult stem cells but not in terminally differentiated cells. NS plays an essential role in maintaining the continuous proliferation of stem cells and some types of cancer cells. However, the role of NS in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to clarify the role of NS in HCC. First, we demonstrated high expression of NS in most HCC cell lines and liver cancer tissues. NS knockdown induced a severe decline in cell viability of MHCC97H cells as detected by MTT and cell proliferation assays. Next, we used ultraviolet (UV) and serum starvation-induced apoptosis models to investigate whether NS suppression or up-regulation affects HCC cell apoptosis. After UV treatment or serum starvation, apoptosis was strongly enhanced in MHCC97H and Bel7402 cells transfected with small interfering RNA against NS, whereas NS overexpression inhibited UV- and serum-induced apoptosis of HCC cells. Furthermore, after UV irradiation, inhibition of NS increased the expression of pro-apoptosis protein caspase 3 and decreased the expression of anti-apoptosis protein Bcl-2. A caspase 3 inhibitor could obviously prevent NS knockdown-induced apoptosis. In conclusion, our study demonstrated overexpression of NS in most HCC tissues compared with their matched surrounding tissues, and silencing NS promoted UV- and serum starvation-induced apoptosis of MHCC97H and Bel7402 cells. Therefore, the NS gene might be a potential therapeutic target of HCC.
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, China; Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, China.
authors.forename: Fuwen
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, China; Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, China; Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, China; Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, China.
authors.forename: Tanjun
authors.initials: T
authors.lastname: Tong
mesh_terms: D000328:Adult; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; C469949:GNL3 protein, human; D009687:Nuclear Proteins; D019204:GTP-Binding Proteins