The transcription factor, early B cell factor 1 (EBF1), plays a vital role in the lineage specification involving early B cell development and the onset of myelodysplastic syndrome (MDS). Therefore, to investigate whether or not EBF1 affects MDS as well as the transcription factor's underlying mechanism, we used CD34+ hematopoietic stem cells in bone marrow from patients with MDS. The extracted cells were then transfected with a series of EBF1, short hairpin RNA against EBF1 (shEBF1), and SB203580 (a specific mitogen-activated protein kinase [MAPK] axis inhibitor). The effects EBF1 gene and MAPK axis had on cell proliferation, apoptosis, and migration were determined by in vitro cell culturing. We made observations that involved EBF1 inhibiting the messenger RNA (mRNA) level of p38 MAPK, increasing the mRNA levels of extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase 5 (ERK5), decreasing the protein expression of Bcl-2-associated X protein (Bax), and finally elevating the protein levels of B cell lymphoma/leukemia-2 (Bcl-2), stem cell factor (SCF), erythropoietin receptor (EpoR), p-ERK, p-JNK, p-ERK5, cyclin D, cyclin E, cyclin-dependent kinase 2 (CDK2), and CDK6, implying that EBF1 may very well have an inhibitory role in the MAPK axis. Another discovery found that EBF1 had a positive effect on the promotion of bone marrow CD34+ cell proliferation as well as its migration, but inhibited the apoptosis of cells. The results we obtained from this study indicated that the EBF1 gene suppresses the activation of the MAPK axis, thereby promoting both the proliferation and migration of bone marrow CD34+ cells as well as inhibiting the associating apoptosis. The effects of the EBF1 gene are likely to present a new therapeutic target in preventing the progression of MDS.
Keywords: EBF1 gene; bone marrow CD34+ cells; cell apoptosis; cell migration; cell proliferation; mitogen-activated protein kinase axis; myelodysplastic syndrome.
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