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Updated: Sep 8, 2025

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

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Published on: August 2, 2018

低氧诱导的染色体阅读器ZMYND8驱动乳腺癌中依赖于HIF的代谢重新连接

Sandhik Nandi¹, Atanu Mondal¹, Ishita Sarkar²

¹Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India.

The Journal of biological chemistry

|September 5, 2025

概括

这项研究揭示了ZMYND8在缺氧乳腺癌中表观遗传驱动无氧糖解,影响免疫规避. 这种表观遗传因子ZMYND8会影响瘤微环境中的乳酸盐产生和CD8+ T细胞活性.

科学领域:

癌症生物学
表观遗传学
代谢调节

背景情况:

乳腺癌的异质性和缺氧导致治疗结果不佳.
瘤缺氧是影响癌症进展和治疗耐药性的关键因素.
了解推动乳腺癌代谢重编程的分子机制对于开发有效疗法至关重要.

研究的目的:

调查ZMYND8在乳腺癌中调节碳水化合物代谢中的作用.
阐明ZMYND8,HIF1α和缺氧乳腺癌细胞的代谢途径之间的关系.
探索ZMYND8介导的代谢变化对瘤免疫微环境的影响.

主要方法:

在乳腺癌细胞和3D多细胞瘤球体 (MCTS) 中低氧条件下的ZMYND8表达的分析.
免疫组织化学评估ZMYND8和HIF1α表达在乳腺癌组织之间的相关性.
测量与糖解相关的基因表达 (HK II,LDHA),代谢流量分析,评估乙CoA和乳酸盐池.
评估ZMYND8对瘤微环境中的免疫细胞入侵和CD8+T细胞活性的影响.

主要成果:

在缺氧下,ZMYND8的表达上调,并且与乳腺癌中的HIF1α呈正相关性.
在缺氧乳腺癌细胞和体内,ZMYND8通过上调Hexokinase II (HK II) 和乳酸脱酶A (LDHA) 来促进无氧糖解.
ZMYND8直接增强LDHA转录,并将新陈代谢转向糖解,增加细胞外酸化和乳酸盐的产生.
ZMYND8诱导的乳酸积累会影响免疫细胞的入侵,并降低瘤微环境中的CD8+ T细胞活性.

结论:

在乳腺癌中,ZMYND8是低氧诱导的新陈代谢重编程的关键调节剂,促进糖解和乳酸生成.
这项研究揭示了表观遗传 (ZMYND8),癌症代谢和免疫规避之间的新联系.
针对ZMYND8介导的表观遗传代谢轴是一个潜在的乳腺癌治疗策略.

关键词:

乳腺癌染色体基因表达葡萄糖代谢葡萄糖分解氧气过低免疫信号乳酸盐转录

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