Ku80 cooperates with CBP to promote COX-2 expression and tumor growth

Oncotarget
Yao XiaoWuguo Deng

Abstract

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung...Continue Reading

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Citations

Dec 31, 2016·Molecular Biology of the Cell·Damiano FantiniPradip Raychaudhuri
Jun 16, 2018·Journal of Cellular Biochemistry·Chengyong DongLiming Wang
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Apr 16, 2021·Cellular and Molecular Life Sciences : CMLS·Sanna AbbasiCaroline Schild-Poulter
Jan 26, 2016·Pharmacology & Therapeutics·Stephanie KaypeeTapas K Kundu

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Methods Mentioned

BETA
pulldown
pull down
X-ray
immunoprecipitation
ChIP
xenografts
acetylation
transfection
immunoprecipitation assay
PCR

Software Mentioned

IPP
Image Plus Pro
SPSS

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