Transcriptional activation of CBFß by CDK11p110 is necessary to promote osteosarcoma cell proliferation.

BACKGROUND: Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. METHODS: In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFß) were further accessed in osteosarcoma. RESULTS: We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFß expression in osteosarcoma cells. The CBFß promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFß is a direct transcriptional target of CDK11. High expression of CBFß is associated with poor outcome in osteosarcoma patients. Expression of CBFß contributes to the proliferation and metastatic behavior of osteosarcoma cells. CONCLUSIONS: These data establish CBFß as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFß pathway may be a promising therapeutic strategy for osteosarcoma treatment.