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在前列腺癌中,Glyoxalase 1表达和甲基素诱导的瘤性压力之间的机制性联系
Alana Battad1, Francisco Nunez1, Mya S Walker1
1Department of Diabetes and Cancer Metabolism, Beckman Research Institute at City of Hope.
bioRxiv : the preprint server for biology
|December 19, 2025
概括
在患有前列腺癌 (PCa) 的非洲裔美国人/黑人 (AA/B) 男人中,甲基素 (MG) 添加物水平升高. 由于GLO1变异导致的MG排毒受损可能会导致AA/B男性的PCa进展.
科学领域:
- 生物化学和分子生物学
- 癌症研究 癌症研究
- 代谢健康差异的差异
背景情况:
- 前列腺癌 (PCa) 不成比例地影响非裔美国人/黑人 (AA/B) 男人,肥胖与死亡率增加有关.
- 肥胖会增加甲基酸盐 (MG),甲基酸盐是一种反应性代谢物,与代谢失调和癌症进展有关.
- MG在DNA,RNA和蛋白质上形成 adducts,可能破坏细胞功能.
研究的目的:
- 调查甲基甘 (MG) 和其解毒酶甘酶1 (GLO1) 在前列腺癌 (PCa) 差异中的作用.
- 探索MG添加物,GLO1遗传变异和种族之间的PCa代谢变化之间的关联.
主要方法:
- 不同种族的PCa患者的量化MG adducts (AA/B与欧洲美国人/EA).
- 在PCa患者中对GLO1 SNP rs1049346进行基因定型,并分析了PCa细胞系EA (C4-2) 和AA/B (MDA-PCa-2b) 中的GLO1表达和活性.
- 通过转录组和代谢分析评估MG对DNA修复,RNA处理和细胞代谢 (糖解,氧化酸化) 的影响.
主要成果:
- 与PCa和非PCa个体的EA男性相比,AA / B男性的PCaMG adducts在AA / B男性中增加.
- 患有PCa的AA/B男性显示GLO1变体rs1049346的频率更高,与MDA-PCa-2b细胞中的GLO1活性降低和MG adducts增加有关.
- MG暴露诱导了明显的代谢重编程和应激反应,包括增加糖解和TXNIP诱导,特别是在AA/B细胞系中.
结论:
- 升高的MG压力和受损的GLO1排毒可能导致PCa进展和AA/B男性的种族差异.
- MG诱导的代谢重编程和改变的应激反应突出了PCa精准医学的潜在治疗点.
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