Mosaic variegated aneuploidy (MVA), which is characterized by an increase in aneuploidy (>25% of cells exhibit near-diploid aneuploidy) and childhood cancers [30]. Five of eight MVA patients were found to have mutations in both alleles of BubR1 gene. Aneuploidy occurred in the pGenesil-CENPE shRNA-treated LO2 cells in this study, for which one potential explain is that the level of CENP-E may affect spindle checkpoint. Once the level of CENP-E protein was decreased, the onset of unaligned chromosomes and aneuploidy was induced in the anaphase. SYN-117 in vitro Completely inactivating the checkpoint would result in cell autonomous lethality because of large loss or

gain of chromosome; however, cells with a weakened checkpoint could survive but exhibit chromosomal instability. In our study, the level of CENP-E protein was down-regulated dramatically, thus the spindle checkpoint of LO2 cells treated with shRNA vector might be subjected to a large degree of damage,

some of which even suffer apoptosis or death. These points are also proved by our MTT result and are consistent with those of Marcel Tanudji [31].   The controversy about the role of reduced CENP-E in hepatocarcinogenesis Beth A.A. Weaver has demonstrated that aneuploidy resulted from CENP-E+/-, which acts as an oncogene as well as a tumour suppressor. Widespread aneuploidy was accompanied by a 50% decrease of spontaneous liver tumours in aged CENP-E+/- mice compare with CENP-E+/+ mice [32]. In the present study, we found that JPH203 cell line CENP-E decreased by about 50% in HCC tissue as compared with that in para-cancerous tissue. Possible explanations for these contradictions may be: (1) Firstly, We tentatively

put forward that the threshold level of CENP-E protein for promoting tumorigenesis might be in the range of 20-50% of the normal. The rate of apoptosis or death increased obviously in LO2 cells, when CENP-E was down-regulated to 15-20% in this study. However, aneuploidy due to reduced CENP-E (about 50% of the normal level) however in CENP-E+/- mouse could act as a tumour suppressor. CENP-E in HCC tissue may be lower than the threshold value and higher than 15-20% of the normal level, and then may be promoting hepatocarcinogenesis.   (2) Secondly, the control samples used in our study may affect our final results. Because the expression level of CENP-E protein in para-cancerous may be lower than that of the normal liver tissue which was unavailable in the present study, the level of CENP-E in HCC tissue may be no higher than 50% of the normal.   (3) Finally, our results supported the following this website hypothesis, as proposed previously by Salmon’s and Yen’s laboratories [33]. A certain level of the waiting-anaphase signal may be required for cells to induce mitotic arrest.