CBP-triggered KDM2B acetylation accelerates the carcinogenesis of colon cancer

Abstract

Lysine (K)-specific demethylase 2B (KDM2B) has been testified to be an oncogene in diverse cancers, which joins in mediating the carcinogenesis of cancers. Nonetheless, the function of KDM2B in colon cancer remains unexplored. The study attempted to disclose the influences of KDM2B acetylation in the progression of colon cancer. SW48 and SUN-C1 cells were transfected with Flag-KDM2B and administrated by trichostatin A and nicotinamide for 24 hr. Immunoprecipitation with a Flag antibody followed by western blot with acetyl-lysine-specific antibody was executed to detect KDM2B acetylation. The correlation between CREB binding protein (CBP) and KDM2B was then investigated. The K-R and K-Q mutants were constructed and the impacts of KDM2B on demethylation of nucleosomal substrates, p21, and puma transcription and the carcinogenesis of colon cancer were probed. CBP immediately evoked KDM2B acetylation at lysine residue 765 in colon cancer cells. Acetylation of KDM2B obviously destroyed the relevance with nucleosomes, demethylation of nucleosomal substrates, and repressed p21 and puma transcription. More important, KDM2B acetylation restrained SUN-C1 cells proliferation and colony formation, meanwhile, hindered cell migration and invasion. Beyond that, the tumor formation was repressed by KDM2B acetylation. The observations testified that CBP-triggered KDM2B acetylation accelerated the carcinogenesis of colon cancer.