{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:58:26Z","timestamp":1792547906549,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":8,"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":["82360571"],"award-info":[{"award-number":["82360571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neutrophil extracellular traps (NETs) are pivotal in the metastasis of non\u2010small cell lung cancer (NSCLC). Our previous research demonstrated that NETs facilitate NSCLC metastasis by triggering the stimulation of the NOD\u2010like receptor protein 3 (NLRP3) inflammasome, which is mediated through the suppression of the long non\u2010coding RNA MIR503HG. However, the precise molecular mechanisms linking MIR503HG to NLRP3 are still not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By employing protein mass spectrometry and the Human TFDB database, key molecules involved in NLRP3 regulation were identified. The involvement of CCAAT enhancer binding protein beta (C\/EBP\u03b2) in NSCLC metastasis was examined in both cellular and animal models. Dual\u2010luciferase and CUT&amp;RUN assays confirmed the mechanism by which C\/EBP\u03b2 controls NLRP3. The regulatory relationship between MIR503HG and C\/EBP\u03b2 was explored through RNA pulldown, RNA immunoprecipitation and coimmunoprecipitation assays. Additionally, methylation\u2010specific PCR and other studies revealed that NETs suppress MIR503HG via DNA methylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that C\/EBP\u03b2 mediates the regulation of NLRP3 by MIR503HG. Further investigation confirmed that C\/EBP\u03b2 promotes the migration and invasion of NSCLC both in vivo and in vitro and is highly expressed in NSCLC tissue. Mechanistically, C\/EBP\u03b2 binds to the NLRP3 promoter to promote NLRP3 expression. Conversely, MIR503HG suppressed C\/EBP\u03b2 expression by facilitating C\/EBP\u03b2 interaction with the E3 ubiquitin ligase RNF43, which in turn reduced NLRP3 expression and NSCLC metastasis. Meanwhile, we investigated the mechanism by which NETs inhibit MIR503HG expression and found that DNA methylation is involved in the suppression of MIR503HG by NETs. Additionally, reversing this methylation partially restored MIR503HG and NLRP3 expression and mitigated the metastatic effects of NETs in NSCLC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study emphasises the critical roles of C\/EBP\u03b2 and DNA methylation in NETs\u2010mediated NSCLC metastasis. These findings unveil C\/EBP\u03b2 and DNA methylation as potential novel targets for NSCLC with high NETs expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>NETs suppress the expression of MIR503HG by inducing promoter DNA methylation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>C\/EBP\u03b2 binds to the NLRP3 promoter to promote NLRP3 expression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MIR503HG inhibits the expression of C\/EBP\u03b2 protein by promoting the interaction between C\/EBP\u03b2 and the E3 ubiquitin ligase RNF43, thereby repressing NLRP3 expression.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70342","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T04:35:58Z","timestamp":1749530158000},"source":"Crossref","is-referenced-by-count":14,"title":["LncRNA MIR503HG regulates NETs\u2010mediated NLRP3 inflammasome activation and NSCLC metastasis by enhancing the ubiquitination of C\/EBP\u03b2"],"prefix":"10.1002","volume":"15","author":[{"given":"Xin","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital of Nanchang University  Nanchang China"},{"name":"Medical Innovation Center The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital of Nanchang University  Nanchang China"},{"name":"Medical Innovation Center The First Affiliated Hospital of Nanchang 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