核呼吸因子1在蛋白酶体抑制疗法下促进多发性骨髓瘤的细胞存活
Tiziana Bruno1, Maria Chiara Cappelletto2,3, Clelia Cortile1,3
1Gene Expression and Cancer Models Unit, Department of Research and Advanced Technologies Translational Research Area, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Blood
|September 8, 2025
概括
研究人员确定核呼吸因子1 (NRF1) 对于多发性骨髓瘤 (MM) 细胞存活至关重要. 针对其调节网络,包括一种新的增强剂,显示出治疗这种无法治愈的血液癌症的希望.
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 多发性骨髓瘤 (MM) 仍然是一个无法治愈的恶性瘤,尽管治疗方面取得了进展.
- 在cis-regulatory元素的表观遗传失调有助于MM进展,但潜在的机制是不清楚的.
研究的目的:
- 阐明MM中表观遗传失调的分子机制.
- 确定MM细胞存活率和治疗点的主调节者.
主要方法:
- 对55名MM患者的CD138+细胞进行高通量测序 (ATAC-seq) 的转化酶可访问染色质的测试.
- 计算足迹分析染色体可访问性动态.
- 在体内异种移植模型测试治疗干预措施.
主要成果:
- 确定核呼吸因子1 (NRF1) 作为MM生存途径的关键调节者.
- NRF1通过编排无处不在的途径来维持蛋白质酶的稳态.
- 发现了一种调节NRF1表达的新型增强剂;向它降低了NRF1水平,并使MM细胞对博特佐米布 (BTZ) 敏感.
- 对抗NRF1增强剂的反感性寡核酸降低了异种移植模型中的瘤负担,并改善了单独或与BTZ一起的存活率.
结论:
- 揭示了一种新的NRF1依赖机制,对多发性髓瘤细胞存活至关重要.
- 针对MM治疗的NRF1调控网络,包括其增强剂的治疗潜力已被证明.
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