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miR-124 radiosensitizes human glioma cells by targeting CDK4

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Abstract

The aberrant expression of cyclin-dependent kinase-4 (CDK4) has previously been observed in human brain glioma. Furthermore, it is observed that up-regulation of CDK4 is associated with therapy resistance and relapse. However, the mechanisms behind these phenomena remain unclear. Here, we demonstrated that elevated CDK4 expression is correlated with poor prognosis in glioma after radiotherapy and that CDK4 knockdown conferred radiosensitivity in glioma cell lines. CDK4 was identified as potential downstream target of miR-124 through bioinformatics analysis and dual-firefly luciferase reporter assay. Furthermore, restoration of miR-124 could confer radiosensitivity. Cell differentiation agent-2 (CDA-2) mimicked the effect of miR-124 restoration and CDK4 knockdown, and sensitized xenografts to radiation in an animal model. Our findings demonstrated for the first time that CDK4 was a downstream target of miR-124 and that CDA-2 could radiosensitize Glioblastoma multiforme cells through the MiR-124-CDK4 axis.

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Acknowledgments

This research was supported by Medical Science and Technology Research Fund of Guangdong Province, China. No. A2011183.

Conflict of interest

The authors have declared that no conflict of interest.

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Authors and Affiliations

  1. Cancer Institute of Southern Medical University, Guangzhou, People’s Republic of China

    Xubin Deng & Lei Ma

  2. Cancer Hospital of Guangzhou Medical College, Guangzhou, People’s Republic of China

    Lei Ma & Chuan Jin

  3. Department of Histology and Embryology, Guangdong Medical College, Zhanjiang, People’s Republic of China

    Minhua Wu

  4. Department of Radiotherapy, People’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China

    Gong Zhang

  5. Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China

    Yuping Guo & Ruilei Liu

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  1. Xubin Deng
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  3. Minhua Wu
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  4. Gong Zhang
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  5. Chuan Jin
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Correspondence to Ruilei Liu.

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Xubin Deng, Lei Ma and Minhua Wu have contributed equally to this study.

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Deng, X., Ma, L., Wu, M. et al. miR-124 radiosensitizes human glioma cells by targeting CDK4. J Neurooncol 114, 263–274 (2013). https://doi.org/10.1007/s11060-013-1179-2

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  • DOI: https://doi.org/10.1007/s11060-013-1179-2

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