title: 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.
authors.affiliation: Department of Labour Hygiene and Sanitary Science, College of Public Health, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Clinical Laboratory Diagnosis Center of PLA, General Hospital of Lanzhou Command, Ürümqi, Xinjiang Uyghur Autonomous Region 830000, P.R. China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Ran
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Shayahati
authors.initials: S
authors.lastname: Bieerkehazhi
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Xiaomiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Jibieke
authors.initials: J
authors.lastname: Watibieke
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Meiliwuerti
authors.initials: M
authors.lastname: Dawulietihan
authors.affiliation: Morphology Center, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Institute, The Affiliated Cancer Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
authors.forename: Huiwu
authors.initials: H
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D007093:Imidazoles / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D000077022:Survivin; D051996:Transcription Factor RelA / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D034741:RNA, Small Interfering; D000077022:Survivin; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; C523798:sepantronium