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

被引:0
作者
MingHua Li
XiaoDan Zhao
Ying Liu
Jun An
Hui Xiao
Chao Wang
机构
[1] The Second Affiliated Hospital of Harbin Medical University,Services of Head and Neck Surgery, Department of Otolaryngology
[2] The Second Affiliated Hospital of Harbin Medical University,Head and Neck Surgery
来源
European Archives of Oto-Rhino-Laryngology | 2017年 / 274卷
关键词
CDK8; Laryngeal squamous cell carcinoma; Migration; Proliferation; Wnt;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:2205 / 2213
页数:8
相关论文
共 184 条
[1]  
Lovato A(2015)Letter on the article “partial laryngectomy as salvage surgery after radiotherapy: oncological and functional outcomes and impact on quality of life. A retrospective study of 20 cases” Eur Ann Otorhinolaryngol Head Neck Dis 132 175-179
[2]  
Rudolph E(2011)Effects of tumour stage, comorbidity and therapy on survival of laryngeal cancer patients: a systematic review and a metaanalysis Eur Arch Otorhinolaryngol 268 165-915
[3]  
Dyckhoff G(2005)Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Endocr Rev 26 898-4045
[4]  
Becher H(2007)Wnt signaling pathway and stem cell signaling network Clin Cancer Res 13 4042-605
[5]  
Dietz A(2002)Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signalling Nat Genet 32 594-940
[6]  
Ramroth H(2004)Expression of adenomatous polyposis coli (APC) in tumorigenesis of human oral squamous cell carcinoma Oral Oncol 40 932-32
[7]  
Mulholland DJ(2006)Roles and regulation of Wnt signaling and beta-catenin in prostate cancer Cancer Lett 237 22-600
[8]  
Dedhar S(2008)Wnt signaling in renal cancer Curr Drug Targets 9 591-237
[9]  
Coetzee GA(2008)RUNX3 attenuates beta-catenin/T cell factors in intestinal tumorigenesis Cancer Cell 14 226-17140
[10]  
Nelson CC(2011)Maintenance of adenomatous polyposis coli (APC)-mutant colorectal cancer is dependent on Wnt/beta-catenin signaling Proc Natl Acad Sci USA 108 17135-220