title: Overexpression of CCAAT Enhancer-Binding Protein α Inhibits the Growth of K562 Cells via the Foxo3a-Bim Pathway.
abstract: We aimed to investigate the role of CCAAT enhancer-binding protein α (C/EBPα) in the pathogenesis of chronic myeloid leukemia (CML) and the mechanism underlying its effect. Bone marrow specimens from 50 patients with CML and peripheral blood specimens from 20 healthy individuals were collected. K562 cells were treated with imatinib. Subsequently, a stable cell line, K562-C/EBPα, was constructed. Cell proliferation was assayed with cell counting kit-8, and mRNA levels of C/EBPα, forkhead transcription factor FKHRL1 (Foxo3a) and Bim were detected by semiquantitative PCR. The correlation of C/EBPα and BCR-ABL was assessed by Spearman's correlation analysis. The results showed that C/EBPα mRNA levels were significantly reduced in CML patients compared with healthy subjects (p < 0.001) and were negatively correlated with BCR-ABL1 (r = -0.5046, p < 0.01). Additionally, imatinib enhanced the expression of C/EBPα in K562 cells compared with untreated cells (p < 0.05). Overexpression of C/EBPα significantly decreased cell proliferation and upregulated the expressions of the apoptosis-related genes Foxo3a (p < 0.01) and Bim (p < 0.05) in K562 cells. In conclusion, C/EBPα expression was decreased in patients with CML. Imatinib enhances the expression of C/EBPα in K562 cells, and the overexpression of C/EBPα inhibits cell proliferation and increases apoptosis via the Foxo3a-Bim pathway.
authors.affiliation: Department of Laboratory, Yantai Yuhuangding Hospital, Medical College, Qingdao University, Yantai, China.
authors.forename: Guili
authors.initials: G
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.forename: Caifu
authors.initials: C
authors.lastname: Luan
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Shao
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Chengming
authors.initials: C
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014162:Transfection
chemical_list: D001549:Benzamides; D022763:CCAAT-Enhancer-Binding Protein-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl