Transcriptional activation of CBFβ 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 (CBFβ) were further accessed in osteosarcoma. RESULTS:We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. CONCLUSIONS:These data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment

MULTI-X, a State-of-the-Art Cloud-Based Ecosystem for Biomedical Research

With the exponential growth of clinical data, and the fast development of AI technologies, researchers are facing unprecedented challenges in managing data storage, scalable processing, and analysis capabilities for heterogeneous multisourced datasets. Beyond the complexity of executing data-intensive workflows over large-scale distributed data, the reproducibility of computed results is of paramount importance to validate scientific discoveries. In this paper, we present MULTIX, a cross-domain research-oriented platform, designed for collaborative and reproducible science. This cloud-based framework simplifies the logistical challenges of implementing data analytics and AI solutions by providing pre-configured environments with ad-hoc scalable computing resources and secure distributed storage, to efficiently build, test, share and reproduce scientific pipelines. An exemplary use-case in the area of cardiac image analysis will be presented together with the practical application of the platform for the analysis of ~20.000 subjects of the UK-Biobank database