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

Abstract

Survivin and transcription factor p65 (NF‑κB p65) participate in the progression of esophageal squamous cell carcinoma (ESCC). However, the mechanism of NF‑κB 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‑κB p65 in ESCC. The expression levels of survivin, NF‑κB p65, inhibitor of nuclear factor κB kinase subunit α (IKKα) and inhibitor of nuclear factor κB kinase subunit β (IKKβ) 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 IKKα, IKKβ and NF‑κB p65. Cell cycle and apoptosis assays were conducted to detect surviving-dependent cellular behavior changes. In addition, the luciferase reporter gene assay and chromatin immunoprecipitation assay were conducted to determine the genomic sites responsible for surviving-induced activation of NF‑κB p65. The present study demonstrated that the expression of survivin is positively correlated with IKKα and IKKβ in ESCC tissues. Survivin affected the mRNA and protein expression levels of IKKα, IKKβ, and NF‑κB p65 in Eca109 and KYSE150 cells. Furthermore, survivin increased the transcriptional activity of the IKKβ promoter and bound to the IKKβ promoter region in the Eca109 cells. Downregulation of survivin arrested the cell cycle at the G2/M phase and induced apoptosis. Results of the present study suggest that survivin activates NF‑κB p65 in Eca109 cells via binding to the IKKβ promoter region and upregulating IKKβ promoter transcriptional activity. Survivin overexpression activates NF‑κB p65, which is important in the acquisition and maintenance of the oncogenic characteristics of ESCC.

High nuclear Survivin expression as a poor prognostic marker in pancreatic ductal adenocarcinoma

“…The survival results support the above ones and those by Xie et al Previously, the positive associations of nuclear Survivin and aggressive phenotypes, such as cell proliferation and microvascular density (MVD) and/or poor prognosis, were also revealed by many papers in many malignant tumors . In vitro investigations showed that nuclear Survivin play its oncogenic role via many molecular mechanisms, such as abrogation of cell‐cycle checkpoints, an increase of DNA repair capacity, and activation of nuclear factor κB (NF‐κB) p65, in cancer cells . The findings provided the biological basis of the negative prognostic value of nuclear Survivin in malignancies.…”

“…nSurvivin, nuclear Survivin expression; G1-2, well-to-moderately differentiated nuclear factor κB (NF-κB) p65, in cancer cells. [38][39][40] The findings provided the biological basis of the negative prognostic value of nuclear Survivin in malignancies. Of particular importance was the fact that nuclear Survivin expression remains to be significant in the multivariate analysis.…”

Bosutinib Acts as a Tumor Inhibitor via Downregulating Src/NF‐κB/Survivin Expression in HeLa Cells

“…Our previous study demonstrated that the expression of survivin is positively correlated with IKKβ in ESCC tissues. Survivin affected the mRNA and protein expression levels of IKKβ, and NF‐κB p65 in Eca109 and KYSE150 cells (Zeng et al, ), and this phenomenon can also been observed in HeLa cells.…”

Inhibitory effect of survivin-shRNA on A431 cutaneous squamous cell carcinoma

“…[9] As to B-cell lymphoma, colorectal cancer and T-cell leukemia, it has been reported that NF-κB can bind to survivin promoter region and result in the enhancement of transcription. [10] Studies by Cui et al [11] showed that in bladder cancer, NF-κB can facilitate cell cycle progression, and the activated NF-κB signaling pathway can help to up-regulate the expression of survivin and then reduce cell apoptosis, thereby increasing cell proliferation. Zeng et al [10] found in the study of esophageal cancer that up-regulating the expression of survivin can increase the upstream gene IKK of P65 at the transcription level and promote the increase in the expression of P65 protein.…”

“…[10] Studies by Cui et al [11] showed that in bladder cancer, NF-κB can facilitate cell cycle progression, and the activated NF-κB signaling pathway can help to up-regulate the expression of survivin and then reduce cell apoptosis, thereby increasing cell proliferation. Zeng et al [10] found in the study of esophageal cancer that up-regulating the expression of survivin can increase the upstream gene IKK of P65 at the transcription level and promote the increase in the expression of P65 protein. On the contrary, it can inhibit the expression of P65 protein, and survivin can bind to IKK promoter region.…”