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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
Gene Expression Profile Regulated by CREB in K562 Cell Line
1Department of Blood Transfusion, Dongtai People's Hospital of Jiangsu Province, Dongtai, Jiangsu, People's Republic of China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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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