基斯H3 K27M介导的调节癌细胞干细胞和差异化在扩散的中线质瘤

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Monika Sharma¹, Ivana Barravecchia¹, Brian Magnuson²

¹Center for Molecular Imaging, The University of Michigan Medical School, Ann Arbor, MI 48109, United States; Department of Radiology, The University of Michigan Medical School, Ann Arbor, MI 48109, United States.

Neoplasia (New York, N.Y.)

|August 30, 2023

概括

扩散中线质瘤 (DMG) 的治疗耐药性与ALDH1A3阳性癌症干细胞有关. H3K27M基素通过抑制瘤抑制剂EYA4驱动茎状和抗性,提供新的治疗点.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
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:

治疗耐药性是H3K27M改变的扩散中线质瘤 (DMG) 的一个重大挑战.
ALDH阳性癌症干细胞 (CSCs),表达高的ALDH1A3,有助于这种抵抗.
目前正在调查H3K27M胆固醇在驱动茎和抵抗中的作用.

研究的目的:

为了研究一种假设,即H3K27M基斯驱动ALDH介导的干性和抗性.
阐明DMG中连接H3K27M,ALDH1A3,Wnt信号和瘤抑制剂EYA4的分子机制.
确定潜在的治疗点,以克服DMG的耐药性.

主要方法:

在DMG模型中删除H3K27M.
评估ALDH1A3表达,天体细胞标记物表达和神经圈形成.
分析基因素乙化,Wnt信号通路活性和EYA4表达 (mRNA和蛋白质).

主要成果:

删除H3K27M导致ALDH1A3表达减少,星球细胞标记物增加,神经圈形成减少,表明分化.
在H3K27M基因组中,通过ALDH1A3以Wnt依赖的方式调节基因乙化.
损失了对放射治疗敏感的H3K27MDMG细胞.
H3K27M抑制了EYA4的表达,导致Wnt信号的升高,并促进了茎状和分化.

结论:

EYA4在DMG中起到瘤抑制作用,而其被H3K27M抑制导致异常Wnt信号传递,调节茎状和分化.
了解H3K27M介导的癌症干和分化的调节,为DMG的新治疗策略提供了理由.
对EYA4过度表达的进一步研究可能会揭示其阻碍DMG生长和入侵的潜力.

关键词:

癌症干细胞是癌症干细胞.扩散的中线质瘤 (DMG)H3K27M 在线阅读放射性敏感化是一种放射性敏感化.电阻电阻电阻电阻电阻电阻

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