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Aberrant expression of CDK8 regulates the malignant phenotype and associated with poor prognosis in human laryngeal squamous cell carcinoma

European Archives of Oto-Rhino-Laryngology volume 274, pages 2205–2213 (2017)Cite this article

Abstract

CDK8, a member of the transcriptional subtype of the cyclin-dependent kinases (CDKs) family, shows remarkable cancer tissue specific expression profile and rather more selective contribution to the regulation of gene expression levels involved in some signaling pathways. However, the effect of CDK8 on the malignant phenotype of human laryngeal squamous cell carcinoma (LSCC) cells and the potential molecular mechanisms remain unclear. In the present study, we evaluated the expression levels of CDK8 by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry in tissue samples of 60 LSCC patients. Then we analyzed and correlated the results with clinicopathological features. We demonstrated that CDK8 was significantly overexpressed in LSCC tissues compared with normal controls, and this overexpression was correlated with lymph node metastasis and advanced clinical stages. Kaplan–Meier analysis showed that high expression levels of CDK8 miRNA significantly correlated with short OS survival. In addition, down-regulation of CDK8 using small interfering RNA(siRNA) reduced the proliferation and migration of LSCC in vitro. To explore the potential mechanism, we investigated the effect of CDK8 on Wnt signaling pathway and found that CDK8 was involved in the EMT progress by regulating β-catenin of the Wnt signaling. In summary, our data suggest for the first time that CDK8 appears to contribute to the malignant mechanism of LSCC and may represent a significant prognostic marker for LSCC patients.

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Acknowledgements

We thank the Department of Otorhinolaryngology at the Second Affiliated Hospital of Harbin Medical University for providing human laryngeal tissue samples.

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    Affiliations

    1. Services of Head and Neck Surgery, Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 148, Bao jian Road, Harbin, 150081, People’s Republic of China

      MingHua Li, Ying Liu, Jun An, Hui Xiao & Chao Wang

    2. Department of Laboratory Diagnosis, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China

      XiaoDan Zhao

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    1. MingHua Li
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    2. XiaoDan Zhao
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    3. Ying Liu
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    Corresponding authors

    Correspondence to Hui Xiao or Chao Wang.

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    Funding

    The study was funded by grants from the Heilongjiang Postdoctoral Fund (LBH-Z14162), the China Postdoctoral Science Fundation (2015M581476) and the National Natural Science Foundation of China (81602368).

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Ethical approval

    The study was approved by the Ethics Committee of Harbin Medical University (No. 2,013,003) and was conducted in accordance with Resolution 196/96 of the Brazilian National Health Council. Informed consent was obtained from all individual participants included in the study.

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    M. Li, X. Zhao contributed equally to this work.

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    Li, M., Zhao, X., Liu, Y. et al. Aberrant expression of CDK8 regulates the malignant phenotype and associated with poor prognosis in human laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 274, 2205–2213 (2017). https://doi.org/10.1007/s00405-017-4484-0

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    • DOI: https://doi.org/10.1007/s00405-017-4484-0

    Keywords

    • CDK8
    • Laryngeal squamous cell carcinoma
    • Migration
    • Proliferation
    • Wnt