多omics整合揭示了eccDNAs在扩散大B细胞淋巴瘤中的致癌作用,通过STING信号传递
Zijuan Wu1,2,3, Wei Zhang1,4, Luqiao Wang5
1Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China.
Clinical and translational medicine
|August 26, 2024
概括
外染色体圆形DNA (eccDNA) 通过激活STING通路来促进扩散性大B细胞淋巴瘤 (DLBCL). DNA损伤诱导eccDNAs,为DLBCL治疗提供了一个治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 异染色体圆形DNA (eccDNA) 涉及疾病进展,但其在扩散性大B细胞淋巴瘤 (DLBCL) 中的作用未报告.
- eccDNAs激活DNA感知通路,影响细胞过程.
研究的目的:
- 研究eccDNAs在DLBCL病变发生中的作用和意义.
- 探索eccDNA激活的机制及其对DLBCL进展的影响.
- 评估针对DLBCL中的eccDNA-STING通路的治疗策略.
主要方法:
- 循环DNA测序 (circle-seq) 和原子力显微镜被用来检测DLBCL中的eccDNA.
- CCK-8和scRNA-seq分析了STING通路和细胞增殖的eccDNA激活.
- 化疗药物和STING抑制剂在体外和体内模型中使用.
主要成果:
- 在DLBCL中,eccDNAs被广泛表达,并且与患者的预后相关.
- 升高的eccDNA水平可以促进DLBCL的进展.
- DNA损伤诱导eccDNAs,激活独立于cGAS的STING信号,增强扩散.
- 联合化疗和STING抑制显示出协同作用的抗瘤效应.
结论:
- 在DLBCL中,DNA损伤诱导的eccDNAs通过激活独立于cGAS的STING信号来发挥瘤性作用.
- 针对STING通路与化疗结合,为DLBCL提供了一个有希望的治疗策略,特别是在复发/耐药病例中.
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