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RAS 反应元件结合蛋白 1 阻止髓系白血病细胞的粒细胞分化。

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

机构信息

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.

出版信息

Oncol Res. 2019 Jul 12;27(7):809-818. doi: 10.3727/096504018X15451301487729. Epub 2019 Apr 8.

DOI:10.3727/096504018X15451301487729
PMID:30982491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7848438/
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- 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, CEBPβ, 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.

摘要

RAS 反应元件结合蛋白 1（RREB1）是一种转录因子，与 RAS 信号和多种肿瘤有关。然而，RREB1 在急性髓系白血病中的作用尚未被研究过。我们发现 RREB1 在 AML 患者和髓系白血病细胞系（NB4 和 HL-60）中过表达，并且在全反式视黄酸（ATRA）诱导的髓系白血病细胞向粒细胞分化过程中 RREB1 的表达显著降低。然后我们在 NB4 和 HL-60 细胞中进行了 RREB1 敲低实验；结果表明，敲低 RREB1 上调了 CD11b、CEBPβ 和 microRNA-145（miR-145）的表达，这表明敲低 RREB1 增强了髓系白血病细胞的粒细胞分化。此外，miR-145 的抑制剂可以抵消下调 RREB1 对粒细胞分化的增强作用。这些综合发现表明，RREB1 通过抑制 miR-145 的表达和 RAS 信号通路的下游靶标来阻止髓系白血病细胞的粒细胞分化。这可能为 AML 患者提供一个有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d9f/7848438/4b79e8d699a3/OR-27-809-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d9f/7848438/4b79e8d699a3/OR-27-809-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d9f/7848438/94603485035c/OR-27-809-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d9f/7848438/64d69c87afb4/OR-27-809-g002.jpg
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