{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:07:50Z","timestamp":1789168070178,"version":"build-2803163510"},"reference-count":121,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis-induced acute lung injury (ALI) remains a leading cause of mortality in critically ill patients and is characterized by dysregulated inflammation, immune imbalance, and alveolar\u2013capillary barrier dysfunction. Emerging evidence suggests that circular RNAs (circRNAs), a class of stable and highly conserved non-coding RNAs, play important regulatory roles in inflammatory diseases; however, their contributions to sepsis-associated lung injury have not yet been systematically summarized. In this review, we provide a comprehensive overview of circRNA biogenesis, classification, and regulatory properties, with a particular focus on their context-dependent functions in the septic lung. We discuss how circRNAs participate in the coordination of cell fate decisions, immune responses, and barrier integrity during sepsis, and highlight their potential as diagnostic biomarkers and therapeutic targets. Importantly, we also address current technical and translational challenges, including detection specificity, disease heterogeneity, and limited clinical validation. By integrating mechanistic insights with translational perspectives, this review aims to clarify the emerging role of circRNAs in sepsis-induced ALI and to outline key directions for future research.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1718164","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:33:34Z","timestamp":1771392814000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Circular RNAs in sepsis-induced acute lung injury: emerging mechanisms and therapeutic potential"],"prefix":"10.3389","volume":"17","author":[{"given":"Qinghai","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitang","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Xu","sequence":"additional","affiliation":[{"name":"Famous Physicians Clinic, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]},{"name":"Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenchun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Critical and Emergency Medicine, Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-024-07694-z","article-title":"Sepsis: key insights, future directions, and immediate goals. A review and expert opinion","volume":"50","author":"Martin-Loeches","year":"2024","journal-title":"Intensive Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2017.5208","article-title":"Defining pediatric sepsis","volume":"172","author":"Schlapbach","year":"2018","journal-title":"JAMA Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e2407064","DOI":"10.1002\/advs.202407064","article-title":"Lactylation of histone H3k18 and egr1 promotes endothelial glycocalyx degradation in sepsis-induced acute lung injury","volume":"12","author":"Lu","year":"2025","journal-title":"Adv Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1186\/s13054-014-0568-z","article-title":"Early activation of pro-fibrotic WNT5A in sepsis-induced acute lung injury","volume":"18","author":"Villar","year":"2014","journal-title":"Crit Care (London England)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60604-7","article-title":"Acute lung injury and the acute respiratory distress syndrome: a clinical review","volume":"369","author":"Wheeler","year":"2007","journal-title":"Lancet (London England)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115835","article-title":"Role of C5a in inflammatory responses","volume":"23","author":"Guo","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S353","DOI":"10.33549\/physiolres.934602","article-title":"Acute lung injury from pathophysiology to treatment","volume":"69","author":"Mokr\u00e1","year":"2020","journal-title":"Physiol Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1209438","article-title":"The role of macrophages polarization in sepsis-induced acute lung injury","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.953195","article-title":"The role of neutrophil extracellular traps in acute lung injury","volume":"13","author":"Scozzi","year":"2022","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1289194","article-title":"Acute lung injury caused by sepsis: how does it happen","volume":"10","author":"Sun","year":"2023","journal-title":"Front Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073630","article-title":"Non-coding RNA-targeted therapy: A state-of-the-art review","volume":"25","author":"Nappi","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"194417","DOI":"10.1016\/j.bbagrm.2019.194417","article-title":"Non-coding RNA regulatory networks","volume":"1863","author":"Panni","year":"2020","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"key":"B13","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1186\/s13054-021-03775-3","article-title":"Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury","volume":"25","author":"Jiao","year":"2021","journal-title":"Crit Care (London England)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.86424","article-title":"ADAR1 protects pulmonary macrophages from sepsis-induced pyroptosis and lung injury through miR-21\/A20 signaling","volume":"20","author":"Zhao","year":"2024","journal-title":"Int J Biol Sci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1097\/JS9.0000000000000789","article-title":"Neutrophil membrane-engineered Panax ginseng root-derived exosomes loaded miRNA 182-5p targets NOX4\/Drp-1\/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies","volume":"110","author":"Ma","year":"2024","journal-title":"Int J Surg (London England)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12943-020-01286-3","article-title":"Circular RNA: metabolism, functions and interactions with proteins","volume":"19","author":"Zhou","year":"2020","journal-title":"Mol Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1016\/j.molcel.2022.03.008","article-title":"Circular RNA migration in agarose gel electrophoresis","volume":"82","author":"Abe","year":"2022","journal-title":"Mol Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.7150\/thno.42174","article-title":"Circular RNA-protein interactions: functions, mechanisms, and identification","volume":"10","author":"Huang","year":"2020","journal-title":"Theranostics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41392-023-01561-x","article-title":"Circular RNA vaccine in disease prevention and treatment","volume":"8","author":"Niu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.11.033","article-title":"The competitive landscape of the dsRNA world","volume":"84","author":"Cottrell","year":"2024","journal-title":"Mol Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature12986","article-title":"The multilayered complexity of ceRNA crosstalk and competition","volume":"505","author":"Tay","year":"2014","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx137","article-title":"Systematic review of computational methods for identifying miRNA-mediated RNA-RNA crosstalk","volume":"20","author":"Li","year":"2019","journal-title":"Briefings Bioinf"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1013239","article-title":"CircRNA-regulated immune responses of asian honey bee workers to microsporidian infection","volume":"13","author":"Zhu","year":"2022","journal-title":"Front Genet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12943-022-01500-4","article-title":"The role of m6A RNA methylation in cancer metabolism","volume":"21","author":"An","year":"2022","journal-title":"Mol Cancer"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e2304895","DOI":"10.1002\/advs.202304895","article-title":"m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia","volume":"10","author":"Wu","year":"2023","journal-title":"Adv Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23262","article-title":"Could circRNA be a new biomarker for pre-eclampsia","volume":"86","author":"Shafabakhsh","year":"2019","journal-title":"Mol Reprod Dev"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12282-017-0793-9","article-title":"CircRNA: a novel type of biomarker for cancer","volume":"25","author":"Zhang","year":"2018","journal-title":"Breast Cancer (Tokyo Japan)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa001","article-title":"The bioinformatics toolbox for circRNA discovery and analysis","volume":"22","author":"Chen","year":"2021","journal-title":"Briefings Bioinf"},{"key":"B29","doi-asserted-by":"publisher","first-page":"155224","DOI":"10.1016\/j.prp.2024.155224","article-title":"Exploring ncRNA-mediated pathways in sepsis-induced pyroptosis","volume":"256","author":"Bhat","year":"2024","journal-title":"Pathol Res Pract"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e19404","DOI":"10.7717\/peerj.19404","article-title":"Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p","volume":"13","author":"Yan","year":"2025","journal-title":"PeerJ"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1515\/med-2022-0417","article-title":"circRNA_0001679\/miR-338-3p\/DUSP16 axis aggravates acute lung injury","volume":"17","author":"Zhu","year":"2022","journal-title":"Open Med (Warsaw Poland)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29558","article-title":"Circular RNA; a new biomarker for breast cancer: A systematic review","volume":"235","author":"Jahani","year":"2020","journal-title":"J Cell Physiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"15330338241285149","DOI":"10.1177\/15330338241285149","article-title":"Circular RNA as diagnostic and prognostic biomarkers in hematological Malignancies systematic review","volume":"23","author":"Gao","year":"2024","journal-title":"Technol Cancer Res Treat"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25169010","article-title":"Sepsis biomarkers: advancements and clinical applications-A narrative review","volume":"25","author":"He","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2021.1887212","article-title":"Circular RNA circ_0003420 mediates inflammation in sepsis-induced liver damage by downregulating neuronal PAS domain protein 4","volume":"43","author":"Xiong","year":"2021","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/iep.12497","article-title":"Circular RNA circVAPA modulates macrophage pyroptosis in sepsis-induced acute lung injury through targeting miR-212-3p\/Sirt1\/Nrf2\/NLRP3 axis","volume":"105","author":"Huang","year":"2024","journal-title":"Int J Exp Pathol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12865-021-00419-7","article-title":"Circular RNA circFADS2 is overexpressed in sepsis and suppresses LPS-induced lung cell apoptosis by inhibiting the maturation of miR-15a-5p","volume":"22","author":"Hong","year":"2021","journal-title":"BMC Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15741","article-title":"Circular RNA VMA21 ameliorates sepsis-associated acute kidney injury by regulating miR-9-3p\/SMG1\/inflammation axis and oxidative stress","volume":"24","author":"Shi","year":"2020","journal-title":"J Cell Mol Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204125","article-title":"The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149\/Smad2 axis","volume":"14","author":"Shen","year":"2022","journal-title":"Aging"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e04532","DOI":"10.1016\/j.heliyon.2020.e04532","article-title":"Circular RNA expression in the lungs of a mouse model of sepsis induced by cecal ligation and puncture","volume":"6","author":"Yuan","year":"2020","journal-title":"Heliyon"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.660269","article-title":"Circular RNA TLK1 promotes sepsis-associated acute kidney injury by regulating inflammation and oxidative stress through miR-106a-5p\/HMGB1 axis","volume":"8","author":"Xu","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac364","article-title":"Deep learning models for disease-associated circRNA prediction: a review","volume":"23","author":"Chen","year":"2022","journal-title":"Briefings Bioinf"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.71840","article-title":"Advances in circular RNA and its applications","volume":"19","author":"Zhao","year":"2022","journal-title":"Int J Med Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1261\/rna.035667.112","article-title":"Circular RNAs are abundant, conserved, and associated with ALU repeats","volume":"19","author":"Jeck","year":"2013","journal-title":"RNA (New York NY)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13253","article-title":"EIciRNA-mediated gene expression: tunability and bimodality","volume":"592","author":"Hu","year":"2018","journal-title":"FEBS Lett"},{"key":"B46","doi-asserted-by":"publisher","first-page":"123066","DOI":"10.1016\/j.talanta.2021.123066","article-title":"Circular RNA detection methods: A minireview","volume":"238","author":"Mi","year":"2022","journal-title":"Talanta"},{"key":"B47","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s40659-020-00309-z","article-title":"The roles of miRNA, lncRNA and circRNA in the development of osteoporosis","volume":"53","author":"Yang","year":"2020","journal-title":"Biol Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"114698","DOI":"10.1016\/j.biopha.2023.114698","article-title":"ncRNA-mediated ceRNA regulatory network: Transcriptomic insights into breast cancer progression and treatment strategies","volume":"162","author":"Yang","year":"2023","journal-title":"Biomed Pharmacother = Biomed Pharmacother"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e1686","DOI":"10.1002\/wrna.1686","article-title":"Time to infer miRNA sponge modules","volume":"13","author":"Zhang","year":"2022","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e1820","DOI":"10.1002\/wrna.1820","article-title":"Regulation of microRNA by circular RNA","author":"Singh","year":"2023","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B51","doi-asserted-by":"publisher","first-page":"113239","DOI":"10.1016\/j.biopha.2022.113239","article-title":"Emerging role of LINC00461 in cancer","volume":"152","author":"Zhang","year":"2022","journal-title":"Biomed Pharmacother = Biomed Pharmacother"},{"key":"B52","doi-asserted-by":"publisher","first-page":"112420","DOI":"10.1016\/j.intimp.2024.112420","article-title":"Unraveling the genetic and molecular landscape of sepsis and acute kidney injury: A comprehensive GWAS and machine learning approach","volume":"137","author":"Yang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e19619","DOI":"10.7717\/peerj.19619","article-title":"Identification of hub genes and prediction of the ceRNA network in adult sepsis","volume":"13","author":"Xue","year":"2025","journal-title":"PeerJ"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.85063","article-title":"Intergenic circRNA circ_0007379 inhibits colorectal cancer progression by modulating miR-320a biogenesis in a KSRP-dependent manner","volume":"19","author":"Long","year":"2023","journal-title":"Int J Biol Sci"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2959","article-title":"Exon-intron circular RNAs regulate transcription in the nucleus","volume":"22","author":"Li","year":"2015","journal-title":"Nat Struct Mol Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0158-7","article-title":"The biogenesis, biology and characterization of circular RNAs","volume":"20","author":"Kristensen","year":"2019","journal-title":"Nat Rev Genet"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.910807","article-title":"High-Throughput Sequencing Strategy for miR-146b-regulated circRNA Expression in Hepatic Stellate Cells","volume":"24","author":"Cheng","year":"2018","journal-title":"Med Sci Monit"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218345","article-title":"Review of single-cell RNA sequencing in the heart","volume":"21","author":"Yamada","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e694","DOI":"10.1002\/ctm2.694","article-title":"Single-cell RNA sequencing technologies and applications: A brief overview","volume":"12","author":"Jovic","year":"2022","journal-title":"Clin Trans Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmae006","article-title":"Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies","volume":"30","author":"Derisoud","year":"2024","journal-title":"Hum Reprod Update"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0071-8","article-title":"Single-cell RNA sequencing technologies and bioinformatics pipelines","volume":"50","author":"Hwang","year":"2018","journal-title":"Exp Mol Med"},{"key":"B62","doi-asserted-by":"publisher","first-page":"111430","DOI":"10.1016\/j.cellsig.2024.111430","article-title":"Noncoding RNA network crosstalk in organ fibrosis","volume":"124","author":"Ling","year":"2024","journal-title":"Cell Signal"},{"key":"B63","doi-asserted-by":"publisher","first-page":"2416604","DOI":"10.1080\/07853890.2024.2416604","article-title":"Construction of circRNA-miRNA-mRNA ceRNA regulatory network and screening of diagnostic targets for tuberculosis","volume":"56","author":"Pu","year":"2024","journal-title":"Ann Med"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e14737","DOI":"10.1111\/cns.14737","article-title":"Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol","volume":"30","author":"Liu","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.11.024","article-title":"Hsa_circ_0004287 inhibits macrophage-mediated inflammation in an N(6)-methyladenosine-dependent manner in atopic dermatitis and psoriasis","volume":"149","author":"Yang","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e1318","DOI":"10.1002\/ctm2.1318","article-title":"ALKBH5\/YTHDF2-mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation","volume":"13","author":"Shao","year":"2023","journal-title":"Clin Trans Med"},{"key":"B67","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.tibtech.2013.04.004","article-title":"ZFN, TALEN, and CRISPR\/Cas-based methods for genome engineering","volume":"31","author":"Gaj","year":"2013","journal-title":"Trends Biotechnol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/s41580-019-0131-5","article-title":"The next generation of CRISPR-Cas technologies and applications","volume":"20","author":"Pickar-Oliver","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jconrel.2022.05.043","article-title":"Circular RNA: An emerging frontier in RNA therapeutic targets, RNA therapeutics, and mRNA vaccines","volume":"348","author":"Liu","year":"2022","journal-title":"J Controlled"},{"key":"B70","doi-asserted-by":"publisher","first-page":"7376","DOI":"10.1038\/s41467-025-62607-y","article-title":"Self-splicing RNA circularization facilitated by intact group I and II introns","volume":"16","author":"Shen","year":"2025","journal-title":"Nat Commun"},{"key":"B71","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1007\/s10735-025-10465-9","article-title":"Circ_0008285 regulates macrophage polarization through miR-375\/MAPK14 axis in sepsis-induced acute lung injury","volume":"56","author":"Li","year":"2025","journal-title":"J Mol Histol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4149\/gpb_2022054","article-title":"Circ_0001498 contributes to lipopolysaccharide-induced lung cell apoptosis and inflammation in sepsis-related acute lung injury via upregulating SOX6 by interacting with miR-574-5p","volume":"42","author":"Hu","year":"2023","journal-title":"Gen Physiol Biophys"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1038\/s42003-024-07072-x","article-title":"Decoding the multiple functions of ZBP1 in the mechanism of sepsis-induced acute lung injury","volume":"7","author":"Gong","year":"2024","journal-title":"Commun Biol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"103194","DOI":"10.1016\/j.redox.2024.103194","article-title":"Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury","volume":"74","author":"Wu","year":"2024","journal-title":"Redox Biol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.956361","article-title":"Ferroptosis in sepsis: The mechanism, the role and the therapeutic potential","volume":"13","author":"Lei","year":"2022","journal-title":"Front Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.69141","article-title":"Neutrophil extracellular traps mediate m(6)A modification and regulates sepsis-associated acute lung injury by activating ferroptosis in alveolar epithelial cells","volume":"18","author":"Zhang","year":"2022","journal-title":"Int J Biol Sci"},{"key":"B77","doi-asserted-by":"publisher","first-page":"152219","DOI":"10.1016\/j.imbio.2022.152219","article-title":"CircEXOC5 promotes ferroptosis by enhancing ACSL4 mRNA stability via binding to PTBP1 in sepsis-induced acute lung injury","volume":"227","author":"Wang","year":"2022","journal-title":"Immunobiology"},{"key":"B78","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol Pathol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29296","article-title":"Circular RNA circC3P1 restrains kidney cancer cell activity by regulating miR-21\/PTEN axis and inactivating PI3K\/AKT and NF- kB pathways","volume":"235","author":"Chen","year":"2020","journal-title":"J Cell Physiol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"100550","DOI":"10.1016\/j.clinsp.2024.100550","article-title":"CircRBM33 competitively binds miR-15a-5p to mediate EZH1 expression to ameliorate sepsis-induced acute lung injury","volume":"80","author":"Lin","year":"2025","journal-title":"Clinics (Sao Paulo Brazil)"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.7150\/thno.71086","article-title":"Pyroptosis in inflammatory diseases and cancer","volume":"12","author":"Rao","year":"2022","journal-title":"Theranostics"},{"key":"B82","doi-asserted-by":"publisher","first-page":"101781","DOI":"10.1016\/j.smim.2023.101781","article-title":"Pyroptosis-induced inflammation and tissue damage","volume":"69","author":"Vasudevan","year":"2023","journal-title":"Semin Immunol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s10735-024-10312-3","article-title":"Circular RNA circVAPA mediates alveolar macrophage activation by modulating miR-212-3p\/Sirt1 axis in acute respiratory distress syndrome","volume":"56","author":"Bao","year":"2024","journal-title":"J Mol Histol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.molcel.2019.02.015","article-title":"RNA circularization diminishes immunogenicity and can extend translation duration in vivo","volume":"74","author":"Wesselhoeft","year":"2019","journal-title":"Mol Cell"},{"key":"B85","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13045-023-01452-2","article-title":"Exosomal circRNA: emerging insights into cancer progression and clinical application potential","volume":"16","author":"Zhang","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.molcel.2019.07.016","article-title":"N6-methyladenosine modification controls circular RNA immunity","volume":"76","author":"Chen","year":"2019","journal-title":"Mol Cell"},{"key":"B87","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.molcel.2021.11.019","article-title":"RNA circles with minimized immunogenicity as potent PKR inhibitors","volume":"82","author":"Liu","year":"2022","journal-title":"Mol Cell"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.7150\/thno.77350","article-title":"Circular RNA cancer vaccines drive immunity in hard-to-treat Malignancies","volume":"12","author":"Li","year":"2022","journal-title":"Theranostics"},{"key":"B89","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.ymeth.2021.02.020","article-title":"The design and synthesis of circular RNAs","volume":"196","author":"Obi","year":"2021","journal-title":"Methods (San Diego Calif)"},{"key":"B90","doi-asserted-by":"publisher","first-page":"2259131","DOI":"10.1080\/08916934.2023.2259131","article-title":"CircFLNA\/miR-214 modulates regulatory T cells by regulating PD-1 in acute lung injury induced by sepsis","volume":"56","author":"Zhong","year":"2023","journal-title":"Autoimmunity"},{"key":"B91","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s13577-025-01258-z","article-title":"Activation of the circAGFG1\/miR-195-5p\/PD-L1 axis induces lung injury in sepsis","volume":"38","author":"Bi","year":"2025","journal-title":"Hum Cell"},{"key":"B92","doi-asserted-by":"publisher","first-page":"101639","DOI":"10.1016\/j.trim.2022.101639","article-title":"Lipopolysaccharide-induced lung cell inflammation and apoptosis are enhanced by circ_0003420\/miR-424-5p\/TLR4 axis via inactivating the NF-\u03baB signaling pathway","volume":"74","author":"Yang","year":"2022","journal-title":"Transplant Immunol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/SHK.0000000000002034","article-title":"CIRCKLHL2 KNOCKDOWN ALLEVIATES SEPSIS-INDUCED ACUTE LUNG INJURY BY REGULATING MIR-29B-3P MEDIATED ROCK1 EXPRESSION DOWN-REGULATION","volume":"59","author":"Li","year":"2023","journal-title":"Shock (Augusta Ga)"},{"key":"B94","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12576-023-00891-3","article-title":"Circ_0114428 knockdown inhibits ROCK2 expression to assuage lipopolysaccharide-induced human pulmonary alveolar epithelial cell injury through miR-574-5p","volume":"74","author":"Zhao","year":"2024","journal-title":"J Physiol Sci JPS"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065093","article-title":"Uridine alleviates sepsis-induced acute lung injury by inhibiting ferroptosis of macrophage","volume":"24","author":"Lai","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.5034","article-title":"CircRNA: A novel potential strategy to treat thyroid cancer (Review)","volume":"48","author":"Zhu","year":"2021","journal-title":"Int J Mol Med"},{"key":"B97","doi-asserted-by":"publisher","first-page":"109440","DOI":"10.1016\/j.intimp.2022.109440","article-title":"CircWDR33 alleviates human pulmonary microvascular endothelial cell injury in sepsis-associated acute lung injury by targeting miR-217-5p\/SERP1 axis","volume":"113","author":"You","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2031406","article-title":"Circular RNA VMA21 ameliorates lung injury in septic rat via targeting microRNA-497-5p\/CD2-associated protein axis","volume":"13","author":"Ke","year":"2022","journal-title":"Bioengineered"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1055\/a-2463-4275","article-title":"CircTLK1 knockdown alleviates cell inflammation and apoptosis by regulating elavl1\/nox4 axis in neonatal sepsis-induced lung injury in mice","volume":"42","author":"Li","year":"2025","journal-title":"Am J Perinatol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1080\/01902148.2024.2429184","article-title":"Whole transcriptome sequencing identifies key lncRNAs, circRNAs and miRNAs in sepsis-associated acute lung injury","volume":"50","author":"Xu","year":"2024","journal-title":"Exp Lung Res"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15685","article-title":"CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR-21","volume":"24","author":"Jiang","year":"2020","journal-title":"J Cell Mol Med"},{"key":"B102","doi-asserted-by":"publisher","first-page":"e3261","DOI":"10.1002\/jgm.3261","article-title":"Protective effects of P2X7R antagonist in sepsis-induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression","volume":"22","author":"Zou","year":"2020","journal-title":"J Gene Med"},{"key":"B103","doi-asserted-by":"publisher","first-page":"e380323","DOI":"10.1590\/acb380323","article-title":"Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766\/eukaryotic initiation factor 5A axis-mediated ATP efflux","volume":"38","author":"Ding","year":"2023","journal-title":"Acta Cirurgica Bras"},{"key":"B104","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12943-024-01968-2","article-title":"Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs","volume":"23","author":"Shi","year":"2024","journal-title":"Mol Cancer"},{"key":"B105","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/cac2.12275","article-title":"Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma","volume":"42","author":"Zhang","year":"2022","journal-title":"Cancer Commun (London England)"},{"key":"B106","doi-asserted-by":"publisher","first-page":"e2309857","DOI":"10.1002\/advs.202309857","article-title":"Hypoxic exosomal circPLEKHM1-Mediated crosstalk between tumor cells and macrophages drives lung cancer metastasis","volume":"11","author":"Wang","year":"2024","journal-title":"Adv Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.11.025","article-title":"Recent advances in polymeric transdermal drug delivery systems","volume":"341","author":"Sabbagh","year":"2022","journal-title":"J Controlled Release"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1088\/2057-1976\/acedb2","article-title":"Nano-based drug delivery system for therapeutics: a comprehensive review","volume":"9","author":"Prakash","year":"2023","journal-title":"Biomed Phys Eng Express"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-020-01219-0","article-title":"Advances in colon-targeted nano-drug delivery systems: challenges and solutions","volume":"43","author":"Naeem","year":"2020","journal-title":"Arch Pharmacal Res"},{"key":"B110","doi-asserted-by":"publisher","first-page":"122991","DOI":"10.1016\/j.lfs.2024.122991","article-title":"Advances in psoriasis research: From pathogenesis to therapeutics","volume":"355","author":"Sugumaran","year":"2024","journal-title":"Life Sci"},{"key":"B111","doi-asserted-by":"publisher","first-page":"125380","DOI":"10.1016\/j.ijpharm.2025.125380","article-title":"Advances in metal-organic framework-based drug delivery systems","volume":"673","author":"Khulood","year":"2025","journal-title":"Int J Pharmaceut"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02393-y","article-title":"Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation","volume":"43","author":"Chen","year":"2025","journal-title":"Nat Biotechnol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175481","article-title":"Lipopolysaccharide-induced model of neuroinflammation: mechanisms of action, research application and future directions for its use","volume":"27","author":"Skrzypczak-Wiercioch","year":"2022","journal-title":"Mol (Basel Switzerland)"},{"key":"B114","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1615\/CritRevImmunol.v31.i5.20","article-title":"LPS-induced cytokine production in human monocytes and macrophages","volume":"31","author":"Rossol","year":"2011","journal-title":"Crit Rev Immunol"},{"key":"B115","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.stem.2024.11.010","article-title":"Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy","volume":"32","author":"Logun","year":"2025","journal-title":"Cell Stem Cell"},{"key":"B116","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13045-019-0829-z","article-title":"Applications of patient-derived tumor xenograft models and tumor organoids","volume":"13","author":"Yoshida","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3590","article-title":"Patient-derived cancer organoid cultures to predict sensitivity to chemotherapy and radiation","volume":"25","author":"Pasch","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B118","doi-asserted-by":"publisher","first-page":"104066","DOI":"10.1016\/j.drudis.2024.104066","article-title":"CircRNA knockdown based on antisense strategies","volume":"29","author":"Aquino-Jarquin","year":"2024","journal-title":"Drug Discov Today"},{"key":"B119","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s12943-024-02124-6","article-title":"Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1","volume":"23","author":"Zang","year":"2024","journal-title":"Mol Cancer"},{"key":"B120","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13273-023-00341-6","article-title":"CircSLCO3A1 depletion ameliorates lipopolysaccharide-induced inflammation and apoptosis of human pulmonary alveolar epithelial cells through the miR-424-5p\/HMGB3 pathway","author":"Li","year":"2023","journal-title":"Mol Cell Toxicol"},{"key":"B121","doi-asserted-by":"publisher","first-page":"109199","DOI":"10.1016\/j.intimp.2022.109199","article-title":"CircPalm2 knockdown alleviates LPS-evoked pulmonary microvascular endothelial cell apoptosis and inflammation via miR-450b-5p\/ROCK1 axis","volume":"113","author":"Mu","year":"2022","journal-title":"Int Immunopharmacol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1718164\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:33:36Z","timestamp":1771392816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1718164\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":121,"alternative-id":["10.3389\/fimmu.2026.1718164"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1718164","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"article-number":"1718164"}}