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

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

SUBMITTER: Feng Y

PROVIDER: S-EPMC6792216 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Transcriptional activation of CBFβ by CDK11<sup>p110</sup> is necessary to promote osteosarcoma cell proliferation.

Feng Yong Y Liao Yunfei Y Zhang Jianming J Shen Jacson J Shao Zengwu Z Hornicek Francis F Duan Zhenfeng Z

Cell communication and signaling : CCS 20191014 1

<h4>Background</h4>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.<h4>Methods</h4>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 immuno ...[more]

PMID: 31610798

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Project description:Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal renewal.

Dataset Information

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

Publications

Transcriptional activation of CBFβ by CDK11<sup>p110</sup> is necessary to promote osteosarcoma cell proliferation.

Similar Datasets

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