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增强子和 MYC 在造血中相互作用。

Enhancers and MYC interplay in hematopoiesis.

机构信息

Blood Bank, Preveza General Hospital, 48100, Preveza, Greece.

Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.

出版信息

J Mol Med (Berl). 2020 Apr;98(4):471-481. doi: 10.1007/s00109-020-01891-1. Epub 2020 Mar 6.

Abstract

Transcription requires the fine interplay between enhancers and transcription factors. Enhancers are able to activate transcription of genes involved in normal cell biology, whereas aberrant enhancer activity leads to oncogenesis. MYC is a well-established proto-oncogene involved in half of human cancers amplifying the output of its targets. The crosstalk between MYC and enhancers is known for many years since the discovery of IgH enhancer juxtaposition with MYC in high-grade lymphomas. Here, we focus mainly in the enhancers surrounding MYC in the 8q24 locus. That region comprises several enhancers that associate with other transcription factors, transmembrane receptors, and fusion genes composing complex regulatory networks aberrantly expressed in almost all types of hematological malignancies. Understanding the nature of these interactions in normal blood cells and in leukemias/lymphomas will expand MYC targeting options in the armamentarium against hematological cancers.

摘要

转录需要增强子和转录因子之间的精细相互作用。增强子能够激活正常细胞生物学中涉及的基因的转录,而异常的增强子活性则导致肿瘤发生。MYC 是一种已被充分证实的原癌基因,涉及半数人类癌症,扩增其靶基因的产物。自发现 IgH 增强子与高级别淋巴瘤中的 MYC 并列以来,MYC 与增强子之间的串扰已为人所知多年。在这里,我们主要关注 8q24 位点周围的 MYC 增强子。该区域包含几个与其他转录因子、跨膜受体和融合基因相关的增强子,这些基因构成了复杂的调控网络,在几乎所有类型的血液恶性肿瘤中异常表达。了解这些在正常血细胞和白血病/淋巴瘤中的相互作用的性质,将扩大针对血液癌症的 MYC 靶向选择。

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