由MYC驱动的线粒体DNA复制数的增加发生在早期,并在前列腺癌进展过程中持续存在
Jiayu Chen1, Qizhi Zheng1, Jessica L Hicks1
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
JCI insight
|November 16, 2023
概括
线粒体DNA拷贝数 (mtDNAcn) 在前列腺癌和癌前病变中增加. 这一发现,使用一种新的现场方法,确定了针对性癌症治疗的潜在漏洞.
科学领域:
- 在瘤学瘤学.
- 线粒体生物学 线粒体生物学
- 遗传学 遗传学 是一个
背景情况:
- 线粒体功能的增加与癌症脆弱性有关.
- 线粒体DNA拷贝数 (mtDNAcn) 影响线粒体的功能.
- 之前的批量方法缺乏细胞类型特异性来测量mtDNAcn.
研究的目的:
- 开发和应用多重现场方法来空间定量特定细胞类型的mtDNAcn.cn.
- 调查前列腺癌进展中的mtDNAcn变化.
- 探索MYC在调节mtDNAcn.cn中的作用.
主要方法:
- 多重体 in situ 杂交用于空间 mtDNA 的量化.
- 对mtDNAcn测量的正交验证方法.
- 分析mtRNA水平和线粒体酶活性.
- 在前列腺癌模型中进行MYC抑制和激活研究.
主要成果:
- 在高度前列腺内皮瘤 (HGPIN),前列腺腺癌 (PCa) 和转移性抵抗割的前列腺癌中,mtDNAcn升高.
- 增加的PCa mtDNAcn与更高的mtRNA水平和酶活性相关.
- 抑制MYC会减少mtDNA复制,而激活MYC会增加瘤前列腺细胞中的mtDNA水平.
- 在胰腺和结肠/直肠的癌前病变中观察到mtDNAcn的升高.
结论:
- 细胞类型特异性mtDNAcn的空间定量是可行的,并且在前列腺癌进展过程中显著增加.
- MYC信号传递是前列腺癌中mtDNA复制和拷贝数的关键调节者.
- 升高的mtDNAcn是多个癌前和癌性组织中保存的特征,这表明它对癌症生物学和治疗具有更广泛的意义.
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