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.

中文翻译：

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CDK11p110 转录激活 CBFβ 对于促进骨肉瘤细胞增殖是必要的。


背景技术细胞周期蛋白依赖性蛋白激酶(CDK)的异常表达是癌症的标志。 CDK11 在癌细胞生长和增殖中起着至关重要的作用。然而，CDK11和CDK11转录调控基因的分子机制很大程度上未知。方法在本研究中，我们利用基因阵列技术进行了全局转录分析，以研究 CDK11 在骨肉瘤中的转录作用。使用启动子荧光素酶测定、染色质免疫沉淀测定和凝胶转移测定来鉴定CDK11的直接转录靶标。核心结合因子β亚基（CBFβ）的临床相关性和功能在骨肉瘤中得到进一步研究。结果我们确定了 CDK11p110（而非 CDK11p58）蛋白质-DNA 相互作用在骨肉瘤细胞 CBFβ 表达调节中的转录作用。 CBFβ启动子荧光素酶测定、染色质免疫沉淀测定和凝胶转移测定证实CBFβ是CDK11的直接转录靶标。 CBFβ 的高表达与骨肉瘤患者的不良预后相关。 CBFβ的表达有助于骨肉瘤细胞的增殖和转移行为。结论 这些数据表明 CBFβ 是 CDK11p110 依赖性肿瘤发生的介质，并表明靶向 CDK11-CBFβ 途径可能是骨肉瘤治疗的一种有前途的治疗策略。