Xia H, Gong Z, Lian Y, Zhou J, Wang X
Department of Blood Transfusion, Dongtai People's Hospital of Jiangsu Province, Dongtai, Jiangsu, People's Republic of China.
Department of Hematology, Dongtai People's Hospital of Jiangsu Province, Dongtai, Jiangsu, People's Republic of China.
Transplant Proc. 2016 Jul-Aug;48(6):2221-34. doi: 10.1016/j.transproceed.2016.04.023.
Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) is a member of the CREB/activation transcription factor 1 family that binds to an octanucleotide cAMP response element consensus sequence in promoters of target genes.
CREB has been shown to regulate a variety of cellular functions, including cell proliferation, survival, apoptosis, differentiation, metabolism, hematopoiesis, immune response, and neuronal activity. CREB was also identified as a proto-oncogene involving in transformation by promoting abnormal proliferation and survival of myeloid cells. To understand the mechanism of CREB functions in leukemogenesis, the transcriptional profiles from a K562 cell line in which CREB was knocked down were analyzed with the use of bioinformatics methods.
DAVID Bioinformatics Resources and Gene Set Enrichment Analysis (GSEA) were performed to identify the targets that are regulated by CREB. A total of 692 genes were up-regulated and 364 genes down-regulated. The up-regulated genes were significantly enriched in pathways of cancer and chronic myeloid leukemia. GSEA analysis showed expression of Notch1 pathway to be decreased and hypoxia-inducible factor (HIF) pathway to be activated.
Our results identified candidate gene sets that could be used to guide research on discovering the mechanism of CREB during leukemogenesis.
环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）是CREB/激活转录因子1家族的成员，可与靶基因启动子中的八核苷酸cAMP反应元件共有序列结合。
CREB已被证明可调节多种细胞功能，包括细胞增殖、存活、凋亡、分化、代谢、造血、免疫反应和神经元活动。CREB还被鉴定为一种原癌基因，通过促进髓系细胞的异常增殖和存活参与细胞转化。为了解CREB在白血病发生中的作用机制，利用生物信息学方法分析了CREB被敲低的K562细胞系的转录谱。
使用DAVID生物信息学资源和基因集富集分析（GSEA）来鉴定受CREB调控的靶点。共有692个基因上调，364个基因下调。上调的基因在癌症和慢性髓性白血病途径中显著富集。GSEA分析显示Notch1途径的表达降低，缺氧诱导因子（HIF）途径被激活。
我们的结果确定了候选基因集，可用于指导白血病发生过程中CREB机制发现的研究。
