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针对INSM1的小分子用于治疗高危神经母细胞瘤

Michael S Lan¹, Chiachen Chen¹

¹Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.

|August 26, 2023

概括

神经母细胞瘤 (NB) 是一种儿童癌症,涉及NMYC瘤基因和INSM1蛋白. 用小分子准INSM1可能为高风险的NB提供新的治疗方法.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

人类神经母细胞瘤 (NB) 是一种常见的儿童脑外瘤,临床结果可变.
在NB中NMYC瘤基因放大与晚期疾病和不良预后相关.
驱动NB进展的精确分子机制仍然不完全理解.

研究的目的:

为了研究INSM1的作用,转录因子,在神经母细胞瘤的发病.
在NB中阐明N-Myc瘤蛋白和INSM1之间的相互作用.
确定针对N-Myc/INSM1通路的潜在治疗策略.

主要方法:

研究了INSM1通过N-Myc.的结合和激活.
通过PI3K/AKT/GSK3β通路分析了INSM1对N-Myc稳定性的调制.
利用INSM1-促进器驱动的光酶选平台来识别小分子.

主要成果:

N-Myc直接与INSM1.1结合并激活它.
通过PI3K/AKT/GSK3β信号通路,INSM1影响N-Myc的稳定性.
确定了15种抑制INSM1表达的小分子,分为四类:细胞信号传递抑制剂,DNA/RNA抑制剂,HDAC抑制剂和心脏糖化物.

结论:

N-Myc和INSM1的相互作用对NB瘤生长和恶性瘤至关重要.
用小分子准INSM1为高风险神经母细胞瘤提供了潜在的治疗途径.
对针对INSM1的新型或重新设计的小分子进行进一步的研究是NB治疗的必要条件.

关键词:

在INSM1中.这就是MYCNCN.生物测试生物测试神经母细胞瘤的神经母细胞瘤神经内分泌神经内分泌小分子分子小分子

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