{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:38:15Z","timestamp":1791581895801,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200213"],"award-info":[{"award-number":["82200213"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170185"],"award-info":[{"award-number":["82170185"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370193"],"award-info":[{"award-number":["82370193"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570184"],"award-info":[{"award-number":["81570184"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211376"],"award-info":[{"award-number":["BK20211376"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Extrachromosomal circular DNAs (eccDNAs), a type of double\u2010stranded 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\u2010cell lymphoma (DLBCL) has not been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Circular DNA sequencing (circle\u2010seq) was used to demonstrate the expression profile of eccDNAs in DLBCL, and atomic force microscopy to validate the presence of eccDNAs. CCK\u20108 and scRNA\u2010seq 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\u2010related genes, and animal models were used to investigate the synergistic effects of DNA damage therapy in combination with STING inhibitors on anti\u2010tumour responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EccDNAs were widely expressed in DLBCL and associated with the prognosis of patients. Elevated abundance of eccDNAs promoted the progression of DLBCL. Chemotherapeutic drugs\u2010induced DNA damage triggered the generation of eccDNAs, resulting in the activation of the STING signalling in a cGAS\u2010independent manner. Moreover, inhibition of STING exerted a synergistic anti\u2010tumour effect with cisplatin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1815","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:44:28Z","timestamp":1724651068000},"source":"Crossref","is-referenced-by-count":11,"title":["Multi\u2010omics integration reveals the oncogenic role of eccDNAs in diffuse large B\u2010cell lymphoma through STING signalling"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-7858","authenticated-orcid":false,"given":"Zijuan","family":"Wu","sequence":"first","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Key Laboratory of Hematology, Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Department of Hematology, Suqian Hospital Jiangsu Province Hospital  Suqian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Leng","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Department of Hematology Affiliated People's Hospital of Jiangsu University  Zhenjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongle","family":"Li","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Key Laboratory of Hematology, Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Fan","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengtao","family":"Zhan","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Key Laboratory of Hematology, Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongning","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology Affiliated Hospital of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Sun","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Fu","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"The Central Research Laboratory The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyong","family":"Li","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Key Laboratory of Hematology, Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-3332","authenticated-orcid":false,"given":"Wenyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Oncology Affiliated Hospital of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-3052","authenticated-orcid":false,"given":"Hui","family":"Jin","sequence":"additional","affiliation":[{"name":"Lymphoma Center, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing Medical University  Nanjing China"},{"name":"Key Laboratory of Hematology, Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2027612"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25789"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation\u20102011.1.498"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.91154"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16720"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201057457\u20105"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1101"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21356"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201021\u20101376"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364\u2010022\u201000399\u20109"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201008200\u2010y"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010021\u201001413\u20108"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100244\u2010x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010021\u201000524\u2010z"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010022\u201000468\u2010w"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201019\u20100761"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201023\u20100329"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100629\u20106"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25432"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201005880\u20105"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.05.020"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010020\u20100678\u20102"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241328"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6690"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201005937\u20105"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.07.009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010022\u201001431\u2010x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006373\u20101"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006464\u2010z"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020010039"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15774"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2014.06.032"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09671"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3906\/biy\u20101908\u201023"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007999"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001224\u20103"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.07.034"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201016\u20102784"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.86792"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201021\u20101963"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201022\u20102235"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15152"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201004009\u2010w"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.09.004"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201011\u20102049"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2021.944"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v99.7.2554"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2022.102443"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.64628"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.1815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T04:32:44Z","timestamp":1736483564000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.1815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/ctm2.1815"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.1815","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]},"article-number":"e1815"}}