染色体外环状 DNA (eccDNA) 是一种双链 DNA (dsDNA)，可促进 DNA 传感机制的激活，与多种疾病的进展和预后有关。虽然 eccDNA 的作用仍然存在争议，但其在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中的重要性尚未有报道。使用循环 DNA 测序 (circle-seq) 来证明 eccDNA 在 DLBCL 中的表达谱，并使用原子力显微镜来验证 eccDNA 在 DLBCL 中的表达谱。验证 eccDNA 的存在。采用 CCK-8 和 scRNA-seq 技术来揭示 STING 通路中 eccDNA 的激活，从而增强细胞增殖。使用化疗药物来检验 DNA 损伤诱导 eccDNA 产生，从而独立于 cGAS 激活 STING 通路的假设。利用GEO数据库验证eccDNA相关基因的预后，并利用动物模型研究DNA损伤治疗联合STING抑制剂对抗肿瘤反应的协同作用。EccDNA在DLBCL中广泛表达，并与患者的预后。 eccDNA 丰度的升高促进了 DLBCL 的进展。化疗药物引起的 DNA 损伤触发了 eccDNA 的生成，导致 STING 信号以不依赖于 cGAS 的方式激活。此外，抑制STING与顺铂发挥协同抗肿瘤作用。DNA损伤诱导的EccDNA通过独立于cGAS激活STING信号在DLBCL中发挥致癌作用。这一发现提供了一种合理的治疗策略，将化疗与靶向 STING 相结合。DNA 损伤诱导的 EccDNA 通过独立于 cGAS 激活 STING 信号，在 DLBCL 中发挥致癌作用。化疗药物与 STING 抑制剂的联合治疗显着延缓了肿瘤进展，为 DLBCL 患者的治疗策略提供了新的见解，特别是复发和/或难治性 (R/R) 患者。© 2024 作者。约翰·威利出版的《临床与转化医学》

Extrachromosomal circular DNAs (eccDNAs), a type of double-stranded DNAs (dsDNAs) that facilitate the activation of the DNA sensing machinery, have been implicated in the progression and prognosis of various diseases. While the roles of eccDNAs remain contentious, their significance in diffuse large B-cell lymphoma (DLBCL) has not been reported.Circular DNA sequencing (circle-seq) was used to demonstrate the expression profile of eccDNAs in DLBCL, and atomic force microscopy to validate the presence of eccDNAs. CCK-8 and scRNA-seq techniques were employed to uncover the activation of eccDNA in the STING pathway, leading to enhanced cell proliferation. Chemotherapeutic drugs were used to test the hypothesis that DNA damage induces the production of eccDNA, thereby activating the STING pathway independent of cGAS. GEO databases were used for verification of the prognosis of the eccDNA-related genes, and animal models were used to investigate the synergistic effects of DNA damage therapy in combination with STING inhibitors on anti-tumour responses.EccDNAs were widely expressed in DLBCL and associated with the prognosis of patients. Elevated abundance of eccDNAs promoted the progression of DLBCL. Chemotherapeutic drugs-induced DNA damage triggered the generation of eccDNAs, resulting in the activation of the STING signalling in a cGAS-independent manner. Moreover, inhibition of STING exerted a synergistic anti-tumour effect with cisplatin.EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. This finding offers a rational therapeutic strategy combining chemotherapy with targeting STING.EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. The combined treatment of chemotherapeutic drugs with STING inhibitor significantly delayed the tumor progression, providing new insights into the therapeutic strategy for patients with DLBCL, particularly the relapsed and/or refractory (R/R) ones.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.