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MYBL2 扩增在乳腺癌中的作用:分子机制与治疗潜力。

MYBL2 amplification in breast cancer: Molecular mechanisms and therapeutic potential.

机构信息

Institute of Cancer and Genomic Science, College of Medical and Dental Sciences, University of Birmingham, UK.

Institute of Cancer and Genomic Science, College of Medical and Dental Sciences, University of Birmingham, UK.

出版信息

Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188407. doi: 10.1016/j.bbcan.2020.188407. Epub 2020 Aug 25.

Abstract

The MYBL2 gene, also known as B-MYB, is essential to regulate vital cellular processes including cell proliferation, differentiation and DNA repair. Changes in these pathways can facilitate cancer development and as such targeting these processes represent an effective method to treat multiple cancer types. Alterations in gene expression have been identified in cancer cells including changes in MYBL2, which appears to be of particular significance in breast cancer (BC) patients. Upregulation of MYBL2 in BC can occur via multiple mechanisms, including changes in regulation by micro RNAs, amplification of the 20q13 gene coding region and single nucleotide polymorphisms in the MYBL2 gene itself or associated genes. Evidence from multiple studies suggests MYBL2 expression could be used as a biomarker for disease severity in BC patients, which could identify those who require a more targeted treatment approach to prevent disease recurrence. In fact, high MYBL2 expression correlates with BC metastasis, worse relapse free survival and shorter overall survival, providing strong evidence that upregulation of MYBL2 functions contributes to more aggressive disease. This review summarises the significance of amplified MYBL2 expression to the development and pathogenesis of BC and suggests ways to target this multifunctional protein as an effective treatment to prevent disease recurrence.

摘要

MYBL2 基因,也称为 B-MYB,对调节细胞增殖、分化和 DNA 修复等重要细胞过程至关重要。这些途径的变化可以促进癌症的发展,因此针对这些过程是治疗多种癌症类型的有效方法。已经在癌细胞中鉴定出基因表达的改变,包括 MYBL2 的改变,在乳腺癌 (BC) 患者中似乎具有特别重要的意义。BC 中 MYBL2 的上调可能通过多种机制发生,包括 microRNAs 调节的改变、20q13 基因编码区的扩增以及 MYBL2 基因本身或相关基因的单核苷酸多态性。多项研究的证据表明,MYBL2 表达可作为 BC 患者疾病严重程度的生物标志物,可识别那些需要更有针对性的治疗方法来预防疾病复发的患者。事实上,高 MYBL2 表达与 BC 转移、无复发生存率更差和总生存率更短相关,这有力地表明 MYBL2 功能的上调有助于疾病更具侵袭性。本综述总结了扩增的 MYBL2 表达对 BC 发展和发病机制的意义,并提出了针对这种多功能蛋白的靶向治疗方法,以有效预防疾病复发。

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