Downregulation of nucleostemin causes G1 cell cycle arrest via a p53-independent pathway in prostate cancer PC-3 cells.
OBJECTIVE
To screen the genes and possible signal transduction pathways with which nucleostemin (NS) interacts and explore the mechanism of NS in prostate cancer.


METHODS
NS-specific short-hairpin RNA expression plasmid was used to downregulate the NS level in PC-3 cells and the changes of cell cycle were studied. After that, oligonucleotide DNA microarray was used to screen the genome changes in PC-3 cells and quantitative real-time PCR was used to further confirm the differentially expressed genes.


RESULTS
Detection of cell cycle showed a decrease of S stage and an increase of G1 stage after downregulation of NS. 219 differentially expressed genes were found and these genes were involved in cell cycle, cell proliferation, signal transduction, cell apoptosis and cell differentiation, and so on. Genes related to cell cycle were discussed emphatically. INK4 family genes (P15, P16, P18) were upregulated while cyclin D1 HDAC1 were downregulated. These genes were tightly related to CDK4/6-cyclin D and pRb-E2F1 complexes.


CONCLUSIONS
NS is an important G1/S checkpoint regulator and it could regulate cell cycles via a p53-independent pathway in prostate cancer.
Liu
Ranlu
R
Tianjin Institute of Urology and Department of Urology, Second Hospital of Tianjin Medical University, Tianjin, China.
Zhang
Zhihong
Z
Xu
Yong
Y
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D016193:G1 Phase / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C469949:GNL3 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019204:GTP-Binding Proteins