Abstract
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.
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