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关于 MYC 和凋亡在 B 细胞淋巴瘤发生中的研究进展:来自鼠模型的启示。

Insights about MYC and Apoptosis in B-Lymphomagenesis: An Update from Murine Models.

机构信息

Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.

出版信息

Int J Mol Sci. 2020 Jun 15;21(12):4265. doi: 10.3390/ijms21124265.

Abstract

The balance between cell survival and cell death represents an essential part of human tissue homeostasis, while altered apoptosis contributes to several pathologies and can affect the treatment efficacy. Impaired apoptosis is one of the main cancer hallmarks and some types of lymphomas harbor mutations that directly affect key regulators of cell death (such as BCL-2 family members). The development of novel techniques in the field of immunology and new animal models has greatly accelerated our understanding of oncogenic mechanisms in MYC-associated lymphomas. Mouse models are a powerful tool to reveal multiple genes implicated in the genesis of lymphoma and are extensively used to clarify the molecular mechanism of lymphoma, validating the gene function. Key features of MYC-induced apoptosis will be discussed here along with more recent studies on MYC direct and indirect interactors, including their cooperative action in lymphomagenesis. We review our current knowledge about the role of MYC-induced apoptosis in B-cell malignancies, discussing the transcriptional regulation network of MYC and regulatory feedback action of miRs during MYC-driven lymphomagenesis. More importantly, the finding of new modulators of apoptosis now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.

摘要

细胞存活和死亡之间的平衡代表了人体组织稳态的重要组成部分,而凋亡的改变会导致多种病理,并可能影响治疗效果。凋亡受损是癌症的主要标志之一,某些类型的淋巴瘤存在直接影响细胞死亡关键调节剂的突变(如 BCL-2 家族成员)。免疫学领域新技术和新动物模型的发展极大地加速了我们对 MYC 相关淋巴瘤致癌机制的理解。小鼠模型是揭示淋巴瘤发生中涉及的多个基因的有力工具,广泛用于阐明淋巴瘤的分子机制,验证基因功能。本文将讨论 MYC 诱导的凋亡的特征,以及最近关于 MYC 直接和间接相互作用物的研究,包括它们在淋巴瘤发生中的协同作用。我们回顾了关于 MYC 诱导的凋亡在 B 细胞恶性肿瘤中的作用的现有知识,讨论了 MYC 的转录调控网络以及 miR 在 MYC 驱动的淋巴瘤发生过程中的调节反馈作用。更重要的是,发现新的凋亡调节剂使研究人员能够将实验室中的发现转化为临床实践,从而积极影响人类健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d637/7352788/d76bacf86950/ijms-21-04265-g001.jpg

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