Survivin activates NF-κB p65 via the IKKβ promoter in esophageal squamous cell carcinoma

Survivin and transcription factor p65 (NF-kappa B p65) participate in the progression of esophageal squamous cell carcinoma (ESCC). However, the mechanism of NF-kappa B p65 activation in ESCC remains to be elucidated. The aim of the present study was to investigate the role of survivin in the activation of NF-kappa B p65 in ESCC. The expression levels of survivin, NF-kappa B p65, inhibitor of nuclear factor kappa B kinase subunit alpha (IKK alpha) and inhibitor of nuclear factor kappa B kinase subunit beta (IKK beta) were detected in ESCC tissue samples. Eca109 and KYSE150 cells were cultured and survivin activity was modulated via transfection with an overexpression plasmid, a small hairpin RNA plasmid and a specific inhibitor. Quantitative reverse transcription-polymerase chain reaction and western blotting assays were conducted to assess the effects of survivin on the expression levels of IKK alpha, IKK beta and NF-kappa B p65. Cell cycle and apoptosis assays were conducted to detect survivin-dependent cellular behavior changes. In addition, the luciferase reporter gene assay and chromatin immunoprecipitation assay were conducted to determine the genomic sites responsible for survivin-induced activation of NF-kappa B p65. The present study demonstrated that the expression of survivin is positively correlated with IKK alpha and IKK beta in ESCC tissues. Survivin affected the mRNA and protein expression levels of IKK alpha, IKK beta, and NF-kappa B p65 in Eca109 and KYSE150 cells. Furthermore, survivin increased the transcriptional activity of the IKK beta promoter and bound to the IKK beta promoter region in the Eca109 cells. Downregulation of survivin arrested the cell cycle at the G(2)G(2)/M phase and induced apoptosis. Results of the present study suggest that survivin activates NF-kappa B p65 in Eca109 cells via binding to the IKK beta promoter region and upregulating IKK beta promoter transcriptional activity. Survivin overexpression activates NF-kappa B p65, which is important in the acquisition and maintenance of the oncogenic characteristics of ESCC.