通过调控MYCN靶向作用于含溴结构域和额外末端结构域的蛋白质以抑制神经母细胞瘤的肿瘤发生
Targeting bromodomain and extra-terminal proteins to inhibit neuroblastoma tumorigenesis through regulating MYCN.
作者信息
Shi Xiyao, Wang Ying, Zhang Longhui, Zhao Wenjie, Dai Xiangpeng, Yang Yong-Guang, Zhang Xiaoling
机构信息
Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun, China.
National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital, Jilin University, Changchun, China.
出版信息
Front Cell Dev Biol. 2022 Sep 16;10:1021820. doi: 10.3389/fcell.2022.1021820. eCollection 2022.
Bromodomain and extra-terminal domain (BET) family proteins play important roles in regulating the expression of multiple proto-oncogenes by recognizing acetylation of histones and non-histone proteins including transcription factors, which subsequently promote tumor cell proliferation, survival, metastasis and immune escape. Therefore, BET family proteins are considered attractive therapeutic targets in various cancers. Currently, blocking of the BET proteins is a widely used therapeutic strategy for amplified high-risk neuroblastoma. Here, we summarized and reviewed the recent research progresses for the critical function of BET proteins, as an epigenetic reader, on tumorigenesis and the therapeutic potential of the BET/BRD4 inhibitors on amplified neuroblastoma. We also discussed the combined therapeutic strategies for BET inhibitor-resistant neuroblastoma.
溴结构域和额外末端结构域（BET）家族蛋白通过识别组蛋白和非组蛋白（包括转录因子）的乙酰化作用，在调节多种原癌基因的表达中发挥重要作用，进而促进肿瘤细胞增殖、存活、转移及免疫逃逸。因此，BET家族蛋白被认为是多种癌症中颇具吸引力的治疗靶点。目前，阻断BET蛋白是扩增性高危神经母细胞瘤广泛应用的治疗策略。在此，我们总结并综述了BET蛋白作为一种表观遗传阅读器在肿瘤发生中的关键作用以及BET/BRD4抑制剂对扩增性神经母细胞瘤的治疗潜力的最新研究进展。我们还讨论了对BET抑制剂耐药的神经母细胞瘤的联合治疗策略。
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