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关键转录因子与 microRNAs 在调控正常和恶性髓系造血中的相互作用。

The interplay between critical transcription factors and microRNAs in the control of normal and malignant myelopoiesis.

机构信息

Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Cancer Lett. 2018 Jul 28;427:28-37. doi: 10.1016/j.canlet.2018.04.010. Epub 2018 Apr 16.

Abstract

Myelopoiesis is a complex process driven by essential transcription factors, including C/EBPα, PU.1, RUNX1, KLF4 and IRF8. Together, these factors are critical for the control of myeloid progenitor cell expansion and lineage determination in the development of granulocytes and monocytes/macrophages. MicroRNAs (miRNAs) are expressed in a cell type and lineage specific manner. There is increasing evidence that miRNAs fine-tune the expression of hematopoietic lineage-specific transcription factors and drive the lineage decisions of hematopoietic progenitor cells. In this review, we discuss recently discovered self-activating and feed-back mechanisms in which transcription factors and miRNAs interact during myeloid cell development. Furthermore, we delineate how some of these mechanisms are affected in acute myeloid leukemia (AML) and how disrupted transcription factor-miRNA interplays contribute to leukemogenesis.

摘要

造血是一个由关键转录因子驱动的复杂过程,包括 C/EBPα、PU.1、RUNX1、KLF4 和 IRF8。这些因子共同控制髓系祖细胞的扩增和粒细胞与单核细胞/巨噬细胞谱系的决定。microRNAs (miRNAs) 以细胞类型和谱系特异性的方式表达。越来越多的证据表明,miRNAs 可以微调造血谱系特异性转录因子的表达,并驱动造血祖细胞的谱系决定。在这篇综述中,我们讨论了最近发现的转录因子和 miRNAs 在髓系细胞发育过程中相互作用的自我激活和反馈机制。此外,我们还描述了这些机制在急性髓系白血病 (AML) 中的变化情况,以及转录因子-miRNA 相互作用的紊乱如何导致白血病的发生。

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