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原发性骨髓瘤的内在表观遗传状态驱动转移
Irtisha Singh1,2,3, Nino Rainusso4, Lyazat Kurenbekova4
1Department of Cell Biology and Genetics, College of Medicine, Texas A&M University, Bryan, TX 77807, USA.
bioRxiv : the preprint server for biology
|November 28, 2023
概括
骨髓瘤 (OS) 转移与原发性瘤中明显的活性染色体景观有关. 这些染色体差异推动了基因表达的变化,为儿科骨癌揭示了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 骨髓瘤 (OS) 是一种常见的儿科骨癌,具有高转移潜力,主要发生在肺部.
- 对于OS转移的分子驱动因素的了解仍然很少,这阻碍了有效的治疗策略.
研究的目的:
- 为了研究初级OS瘤的活性染色质景观.
- 确定与OS转移潜力相关的表观遗传差异.
- 发现OS病原和转移背后的新型分子机制.
主要方法:
- 从OS瘤中对基因组H3 lysine乙化染色体 (H3K27ac),染色体可访问性和基因表达数据的综合分析.
- 从有转移和没有转移的患者中对原发性瘤进行比较分析.
- 在转移性肺病变中分析染色质活性.
主要成果:
- 截然不同的活性染色体景观区分了具有或没有转移的初级OS瘤.
- 差异色素活性与转录性变化相关,识别了PPP1R1B,PREX1和IGF2BP1.1等关键基因.
- 在初级转移性瘤中,染色质的改变在参与actin细胞骨架组织,细胞粘附和细胞外矩阵重塑的基因附近得到丰富.
- 转移性肺病变显示了与细胞迁移和Wnt信号传递相关的基因中的染色质活性增加.
结论:
- 转移潜力是原发性OS瘤的内在特征,是由它们的染色质景观塑造的.
- 在OS瘤中的表观遗传适应促进了在远部位的传播,迁移和殖民.
- 向色素修饰可能为预防和治疗OS转移提供新的治疗途径.
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