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RAS-Responsive Element-Binding Protein 1 Blocks the Granulocytic Differentiation of Myeloid Leukemia Cells

Juanjuan Yao*, Liang Zhong, Pengqiang Zhong*, Dongdong Liu, Zhen Yuan, Junmei Liu*, Shifei Yao*, Yi Zhao*, Min Chen*, Lianwen Li*, Lu Liu, Beizhong Liu*†

* Central Laboratory of Yong Chuan Hospital, Chongqing Medical University, Chongqing, P.R. China
† Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China

Oncology Research 2019, 27(7), 809-818. https://doi.org/10.3727/096504018X15451301487729

Abstract

RAS-responsive element-binding protein 1 (RREB1) is a transcription factor that is implicated in RAS signaling and multiple tumors. However, the role of RREB1 in acute myeloid leukemia has not been studied. We found that RREB1 is overexpressed in AML patients and myeloid leukemia cell lines (NB4 and HL-60), and RREB1 expression was significantly decreased during granulocytic differentiation of myeloid leukemia cells induced by all-trans retinoic acid (ATRA). Then we performed a RREB1 knockdown assay in NB4 and HL-60 cells; the results showed that knockdown of RREB1 upregulated expression of CD11b, CEBP , and microRNA-145 (miR-145), which hinted that knockdown of RREB1 enhanced granulocytic differentiation of myeloid leukemia cells. In addition, inhibitor of miR-145 can offset the enhanced effect on granulocytic differentiation mediated by downregulation of RREB1. These collective findings demonstrated that RREB1 blocks granulocytic differentiation of myeloid leukemia cells by inhibiting the expression of miR-145 and downstream targets of the RAS signal pathway. These may provide a promising therapeutic target for AML patients.

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Cite This Article

Yao, J., Zhong, L., Zhong, P., Liu, D., Yuan, Z. et al. (2019). RAS-Responsive Element-Binding Protein 1 Blocks the Granulocytic Differentiation of Myeloid Leukemia Cells. Oncology Research, 27(7), 809–818.



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