Aberrant expression of CDK8 regulates the malignant phenotype and associated with poor prognosis in human laryngeal squamous cell carcinoma
Aberrant expression of CDK8 regulates the malignant phenotype and associated with poor prognosis in human laryngeal squamous cell carcinoma
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CDK8的异常表达调节恶性表型并与人喉鳞状细胞癌的不良预后相关
DOI：
10.1007/s00405-017-4484-0
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发表时间：
2017-05-01
影响因子：
2.6
通讯作者：
Wang, Chao
中科院分区：
文献类型：
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作者：
Li, MingHua;Zhao, XiaoDan;Wang, Chao
CDK 8是细胞周期蛋白依赖性激酶（cyclin-dependent kinases，CDK）家族的一个转录亚型，具有显著的肿瘤组织特异性表达谱，并对某些信号通路中的基因表达水平具有更高的选择性调节作用。然而，CDK 8对人喉鳞状细胞癌（LSCC）细胞恶性表型的影响及其可能的分子机制尚不清楚。在本研究中，我们评估了CDK 8的表达水平，定量实时逆转录聚合酶链反应（qRT-PCR）和免疫组化在60例喉鳞癌患者的组织样本。将结果与临床病理特征进行相关性分析。我们发现，与正常对照相比，CDK 8在喉鳞状细胞癌组织中显著过表达，并且这种过表达与淋巴结转移和晚期临床分期相关。Kaplan-Meier分析显示CDK 8 miRNA的高表达水平与短OS生存期显著相关。此外，使用小干扰RNA（siRNA）下调CDK 8在体外降低了LSCC的增殖和迁移。为了探讨其可能的机制，我们研究了CDK 8对Wnt信号通路的影响，发现CDK 8通过调节Wnt信号通路中的β-catenin参与EMT的进程。总之，我们的数据首次表明，CDK 8似乎有助于喉鳞状细胞癌的恶性机制，并可能代表一个重要的预后标志物喉鳞状细胞癌患者。
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.