Expression and regulation of CacyBP/SIP in chronic lymphocytic leukemia cell balances of cell proliferation with apoptosis.

PURPOSE: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, with incidence in Chinese populations also increasing. CLL involves an accumulation of abnormal B cells which result in dysregulation of cell proliferation and apoptosis rates. The calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) plays a pivotal role in tumorigenicity and cell apoptosis. Here, we investigated the function of CacyBP/SIP in CLL cell proliferation and apoptosis.
METHODS: CacyBP/SIP expression levels were measured in peripheral blood mononuclear cells from 23 Chinese CLL patients and three healthy donors by western blotting. Correlation analysis was performed to assess associations between CacyBP/SIP expression and clinical stage, chromosome abnormalities and zeta-chain-associated protein kinase 70 (ZAP-70) expression. We silenced CacyBP/SIP expression in MEC-1 cells using a lentivirus system and analyzed cell vitality, cell cycle and tumorigenicity. Apoptosis was also analyzed following the upregulation of CacyBP/SIP expression in MEC-1 cells.
RESULTS: Downregulation of CacyBP/SIP expression in CLL patients was negatively correlated with CLL clinical stage, but not with patient sex, age, del(13q14) or del(17q-) presence, or ZAP-70 expression. CacyBP/SIP silencing significantly enhanced cell proliferation and tumorigenicity. CacyBP/SIP silencing promoted accumulation of cells in S phase by upregulation of β-catenin, cyclin D1 and cyclin E, and downregulation of p21. Moreover, CacyBP/SIP overexpression facilitated CLL apoptosis through the activation of pro-caspase-3.
CONCLUSION: CacyBP/SIP is a useful indicator of CLL disease processes and plays an important role in sustaining the balance of cell proliferation and apoptosis.