EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome through negative regulation of mitogen‐activated protein kinase axis
Authors: Yan-Yu Wang
Xi Liu
Bing-Bing Zhao
Ye Yao
Zhi-Lan Zou
Gong-Wei Xiao
Hong Xiong
Shuang Hou
Jie Hao
Yan-Qing Li
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: EBF1 gene; bone marrow CD34+ cells; cell apoptosis; cell migration; cell proliferation
Affiliations: Department of Hematology Shanghai Xuhui Central Hospital Shanghai China, Department of Hematology Shanghai Jingan North Station Hospital Shanghai China

Abstract:  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. 

Retracted: Yes

PubPeer comments:
 Fig 3A.  Gray value analysis of 9 Western blot plots of EBF1u2010related and MAPKu2010related genes among 6 groups . ![file] The loading control is suggestive of a papermill provenance for this paper, as it has appeared in numerous other papers from otherwise-unrelated researchers. Picking two example at random: Fig 8A from [Wu et al (2018)] , Fig 3C of [Luo et al (2018)] : ![] ![] Many more examples in that thread, and in a Google document: https: docs.google.com spreadsheets d 1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY edit?usp=sharing , 
 Fig 8A. In further evidence for a papermill provenance, versions of these flow-cytometry cell-cycle diagrams are also common within this oeuvre. ![file] Picking two examples at random, Fig. 10A from [Zhang et al (2018)] and 9A C from [Qian et al (2018)] . ![] ![] , 
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 18 October 2018 in Wiley Online Library has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,