{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:16:46Z","timestamp":1787170606623,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82272383"],"award-info":[{"award-number":["82272383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32070189"],"award-info":[{"award-number":["32070189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"crossref","award":["2024JJ5341"],"award-info":[{"award-number":["2024JJ5341"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hunan Provincial Health High-Level Talent Scientific Research Project","award":["R2023056"],"award-info":[{"award-number":["R2023056"]}]},{"DOI":"10.13039\/501100010083","name":"Hunan Provincial Innovation Foundation for Postgraduate","doi-asserted-by":"crossref","award":["CX20251423"],"award-info":[{"award-number":["CX20251423"]}],"id":[{"id":"10.13039\/501100010083","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Excellent Youth Project of Hunan Provincial Department of Education","award":["24B0407"],"award-info":[{"award-number":["24B0407"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Pyroptosis enables host cells to eliminate intracellular pathogens effectively. However, how Chlamydia trachomatis (C. trachomatis) evades host pyroptosis remains unclear. This study reveals that C. trachomatis exploits the host Long non-coding RNA (lncRNA) SBF2-AS1 as a key factor to regulate the host pyroptosis. The SBF2-AS1 was significantly upregulated during C. trachomatis infection. Knockdown of SBF2-AS1 activated NLRP3\/caspase-1\/GSDMD pyroptosis pathway. Mechanistically, it verified that SBF2-AS1 functions as a competing endogenous RNA for miR-196b-5p targeting RIPK2 through dual-luciferase reporter gene assay. We further identified the interaction between RIPK2 and Caspase-1 by Co-immunoprecipitation (Co-IP). Silencing SBF2-AS1 or RIPK2, as well as overexpressing miR-196b-5p, triggered pyroptosis and suppressed the replication of C. trachomatis. In conclusion, C. trachomatis upregulates SBF2-AS1 to increase RIPK2 by binding miR-196b-5p, which shields against pyroptosis mediated by Caspase-1 to promote its proliferation. These results uncover a novel mechanism of pathogen\u2013host interaction and provide insights for developing new therapeutic strategies against C. trachomatis infection.<\/jats:p>","DOI":"10.3390\/microorganisms14020459","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:52:21Z","timestamp":1770979941000},"page":"459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LncRNA SBF2-AS1 Regulates Pyroptosis to Promote Chlamydia trachomatis Growth Through miR-196b-5p\/RIPK2 Axis"],"prefix":"10.3390","volume":"14","author":[{"given":"Hongrong","family":"Wu","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, School of Nursing, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, School of Nursing, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewei","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, School of Nursing, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Lei","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, School of Nursing, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, School of Nursing, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, School of Nursing, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.15698\/mic2016.09.525","article-title":"Chlamydia trachomatis Genital Infections","volume":"3","author":"Ferone","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41579-023-00860-y","article-title":"Intracellular lifestyle of Chlamydia trachomatis and host-pathogen interactions","volume":"21","author":"Stelzner","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1038\/s41418-025-01527-2","article-title":"RING1 dictates GSDMD-mediated inflammatory response and host susceptibility to pathogen infection","volume":"32","author":"Li","year":"2025","journal-title":"Cell Death Differ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41580-025-00837-0","article-title":"Mechanistic insights into gasdermin-mediated pyroptosis","volume":"26","author":"Bai","year":"2025","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"EMBJ2019102065","DOI":"10.15252\/embj.2019102065","article-title":"Chopping GSDMD: Caspase-8 has joined the team of pyroptosis-mediating caspases","volume":"38","author":"Gram","year":"2019","journal-title":"EMBO J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0966-842X(00)01937-5","article-title":"Salmonella-induced cell death: Apoptosis, necrosis or programmed cell death?","volume":"9","author":"Boise","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0966-842X(00)01936-3","article-title":"Pro-inflammatory programmed cell death","volume":"9","author":"Cookson","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jiang, P., Chen, H., Feng, X., Xie, H., Jiang, M., Xu, D., Tang, H., Zhang, N., Chen, J., and Zhang, L. (2023). GSDMD-mediated pyroptosis restrains intracellular Chlamydia trachomatis growth in macrophages. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1116335"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chu, B.X., Li, Y.N., Liu, N., Yuan, L.X., Chen, S.Y., Zhu, Y.H., and Wang, J.F. (2021). Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt with SopB. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.757909"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eabq0132","DOI":"10.1126\/science.abq0132","article-title":"A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin","volume":"378","author":"Chai","year":"2022","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1128\/mBio.00595-19","article-title":"Chlamydia trachomatis Lipopolysaccharide Evades the Canonical and Noncanonical Inflammatory Pathways to Subvert Innate Immunity","volume":"10","author":"Yang","year":"2019","journal-title":"mBio"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7493","DOI":"10.1038\/s41467-025-62762-2","article-title":"CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death","volume":"16","author":"Arunima","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.1038\/s41467-025-60084-x","article-title":"A searchable atlas of pathogen-sensitive lncRNA networks in human macrophages","volume":"16","author":"Schmerer","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41419-021-04484-z","article-title":"METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA","volume":"13","author":"Meng","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xia, X., Hou, J., Ren, P., Liu, M., Wang, L., Wei, X., Teng, Z., Kasianenko, O., Cheng, L., and Hu, J. (2023). Coexpression analysis of lncRNAs and mRNAs identifies potential regulatory long noncoding RNAs involved in the inflammatory effects of lipopolysaccharide on bovine mammary epithelial cells. BMC Vet. Res., 19.","DOI":"10.1186\/s12917-023-03780-4"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/s41423-022-00878-x","article-title":"Lnc-EST12, which is negatively regulated by mycobacterial EST12, suppresses antimycobacterial innate immunity through its interaction with FUBP3","volume":"19","author":"Yao","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6713","DOI":"10.1038\/s41598-025-91296-2","article-title":"LncRNA-Gm17586 inhibits S. typhimurium mediated pyroptosis by promoting NLRP3 and Tnip1 binding","volume":"15","author":"An","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wen, Y., Luo, F., Zhao, L., Su, S., Lei, W., Liu, Y., Shi, K., and Li, Z. (2021). Long Non-Coding RNA FGD5-AS1 Induced by Chlamydia trachomatis Infection Inhibits Apoptosis via Wnt\/\u03b2-Catenin Signaling Pathway. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.701352"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.14715\/cmb\/2023.69.14.33","article-title":"Knocking down of lncRNA SBF2-AS1 inhibits proliferation, invasion and induces apoptosis of colorectal cancer through regulating PTEN","volume":"69","author":"Cai","year":"2023","journal-title":"Cell. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/mc.23358","article-title":"Low expression of lncRNA SBF2-AS1 regulates the miR-302b-3p\/TGFBR2 axis, promoting metastasis in laryngeal cancer","volume":"61","author":"Li","year":"2022","journal-title":"Mol. Carcinog."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.omtn.2019.04.004","article-title":"Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma","volume":"16","author":"Chen","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e23629","DOI":"10.1002\/jbt.23629","article-title":"Mechanism of non-small cell lung cancer cell-derived exosome miR-196b-5p promoting pyroptosis of tumor T cells and tumor cell proliferation by downregulating ING5","volume":"38","author":"Zhang","year":"2024","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41419-023-06132-0","article-title":"LncRNA Neat1 targets NonO and miR-128-3p to promote antigen-specific Th17 cell responses and autoimmune inflammation","volume":"14","author":"Chen","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1080\/21505594.2021.1953851","article-title":"Acinetobacter baumannii up-regulates LncRNA-GAS5 and promotes the degradation of STX17 by blocking the activation of YY1","volume":"12","author":"An","year":"2021","journal-title":"Virulence"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2545563","DOI":"10.1080\/21505594.2025.2545563","article-title":"LncRNA-CFTBS enhances Mycobacterium tuberculosis survival in macrophages by modulating ferroptosis through the miR-515-5p\/miR-519e-5p\/SAT1 axis","volume":"16","author":"Li","year":"2025","journal-title":"Virulence"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1080\/21691401.2019.1608221","article-title":"Long noncoding RNA SBF2-AS1 act as a ceRNA to modulate cell proliferation via binding with miR-188-5p in acute myeloid leukemia","volume":"47","author":"Tian","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/jbmr.4834","article-title":"miR-196b-5p Regulates Osteoblast and Osteoclast Differentiation and Bone Homeostasis by Targeting SEMA3A","volume":"38","author":"Xie","year":"2023","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1073\/pnas.1917531117","article-title":"miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer","volume":"117","author":"Liang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41419-020-02997-7","article-title":"miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling","volume":"11","author":"Huang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1038\/s41388-025-03356-6","article-title":"sEV-mediated intercellular transformation from MGAT4A(High) to MGAT4A(Low) tumor cells via the HOTAIRM1\/miR-196b-5p axis promotes apoptosis resistance in CTCL","volume":"44","author":"Sun","year":"2025","journal-title":"Oncogene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e50400","DOI":"10.15252\/embr.202050400","article-title":"A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity","volume":"21","author":"Heim","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_33","first-page":"196","article-title":"lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1","volume":"44","author":"Zhao","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","first-page":"166","article-title":"Exosomal transfer of long non-coding RNA SBF2-AS1 enhances chemoresistance to temozolomide in glioblastoma","volume":"38","author":"Zhang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/21505594.2022.2044666","article-title":"LncRNA ZEB1-AS1\/miR-1224-5p \/ MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection","volume":"13","author":"Luo","year":"2022","journal-title":"Virulence"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/2\/459\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T05:23:39Z","timestamp":1771133019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/2\/459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["microorganisms14020459"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14020459","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]}}}