{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T02:14:54Z","timestamp":1777083294977,"version":"3.51.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"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:sec><jats:title>Background and purpose<\/jats:title><jats:p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition marked by high recurrence and limited therapeutic efficacy. This study investigates the role of long non-coding RNA NEAT1 in promoting epithelial\u2013mesenchymal transition (EMT) in CRSwNP, focusing on its regulatory interaction with the miR-199-3p\/PAK4 axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NEAT1 expression was assessed in nasal epithelial cells from CRSwNP patients using qPCR and FISH. Primary human nasal epithelial cells and BEAS-2B cells were subjected to NEAT1 knockdown via siRNA. Cell migration, barrier function, and cytoskeletal dynamics were evaluated through scratch assays, Transwell migration, FITC-Dextran permeability testing, and phalloidin staining. EMT marker expression was analyzed via Western blotting and immunofluorescence. Transcriptome sequencing identified PAK4 as a downstream effector. <jats:italic>In vivo<\/jats:italic> validation was performed using a mouse nasal polyp model, and molecular interactions among NEAT1, miR-199-3p, and PAK4 were confirmed via dual-luciferase reporter assays. Rescue experiments further elucidated mechanistic pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In comparison to controls, NEAT1 expression was significantly elevated in the epithelial tissues of CRSwNP. NEAT1 knockdown inhibited cell migration, enhanced epithelial barrier integrity, and reversed EMT-associated cytoskeletal remodeling. E-cadherin levels increased, while N-cadherin and vimentin decreased. Transcriptomic and functional analyses identified PAK4 as a NEAT1-regulated target. NEAT1 was shown to sponge miR-199-3p, thereby relieving its inhibitory effect on PAK4. Overexpression of miR-199-3p suppressed PAK4 and mitigated EMT-related changes induced by NEAT1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NEAT1 promotes EMT in nasal polyp epithelial cells by modulating the miR-199-3p\/PAK4 axis, highlighting its potential as a diagnostic biomarker and therapeutic target in CRSwNP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1613179","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T04:10:50Z","timestamp":1751256650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["LncRNA NEAT1 promotes epithelial\u2013mesenchymal transition in nasal polyp cells via the miR-199-3p\/PAK4 axis"],"prefix":"10.3389","volume":"16","author":[{"given":"Shuman","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/j.jaip.2021.09.037","article-title":"Olfactory outcomes with dupilumab in chronic rhinosinusitis with nasal polyps","volume":"10","author":"Mullol","year":"2022","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B2","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/alr.23234","article-title":"Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents\u2019 efficacy","volume":"14","author":"Papacharalampous","year":"2024","journal-title":"Int Forum Allergy Rhinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.04.012","article-title":"Chronic rhinosinusitis with nasal polyps","volume":"4","author":"Stevens","year":"2016","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.07.019","article-title":"Consultation for chronic rhinosinusitis with nasal polyps and asthma: clinical presentation, diagnostic workup, and treatment options","volume":"12","author":"Peters","year":"2024","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jaci.2020.11.013","article-title":"EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management","volume":"147","author":"Bachert","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jaci.2024.11.011","article-title":"Anti-IgE therapy in chronic rhinosinusitis with nasal polyps","volume":"155","author":"Chhiba","year":"2025","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41572-020-00218-1","article-title":"Adult chronic rhinosinusitis","volume":"6","author":"Bachert","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-052016-100401","article-title":"Immunopathogenesis of chronic rhinosinusitis and nasal polyposis","volume":"12","author":"Schleimer","year":"2017","journal-title":"Annu Rev Pathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.12.021","article-title":"Phenotypes of chronic rhinosinusitis","volume":"8","author":"Cho","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/alr.23215","article-title":"miR-200a-3p regulates epithelial-mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK\/p38 pathway","volume":"14","author":"Wu","year":"2024","journal-title":"Int Forum Allergy Rhinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.07.002","article-title":"Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease","volume":"37","author":"Shen","year":"2022","journal-title":"J Adv Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.09.009","article-title":"The prognostic miR-532-5p-correlated ceRNA-mediated lipid droplet accumulation drives nodal metastasis of cervical cancer","volume":"37","author":"Shang","year":"2022","journal-title":"J Adv Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41419-020-03327-7","article-title":"Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer","volume":"12","author":"Parfenyev","year":"2021","journal-title":"Cell Death Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12943-022-01555-3","article-title":"Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m(6)A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression","volume":"21","author":"Liu","year":"2022","journal-title":"Mol Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/s13046-020-01783-9","article-title":"HDAC2 inhibits EMT-mediated cancer metastasis by downregulating the long noncoding RNA H19 in colorectal cancer","volume":"39","author":"Hu","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00471","article-title":"Long non-coding RNA NEAT1: A novel target for diagnosis and therapy in human tumors","volume":"9","author":"Dong","year":"2018","journal-title":"Front Genet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.07.053","article-title":"The lncRNA NEAT1 facilitates cell growth and invasion via the miR-211\/HMGA2 axis in breast cancer","volume":"105","author":"Li","year":"2017","journal-title":"Int J Biol Macromol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02474-w","article-title":"LncRNA NEAT1 antagonizes the inhibition of melanoma proliferation, migration, invasion and EMT by Polyphyllin B","volume":"396","author":"Wang","year":"2023","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.02.029","article-title":"Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells","volume":"12","author":"Song","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.261","article-title":"A novel interaction of PAK4 with PPAR\u03b3 to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma","volume":"36","author":"Kesanakurti","year":"2017","journal-title":"Oncogene"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-025-02085-3","article-title":"PAK4 promotes the cytoskeletal organization and meiotic maturation via phosphorylating DDX17 in oocyte","volume":"23","author":"Wang","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.12.019","article-title":"Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer","volume":"10","author":"Li","year":"2023","journal-title":"Genes Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12341","article-title":"DACT2 silencing by promoter CpG methylation disrupts its regulation of epithelial-to-mesenchymal transition and cytoskeleton reorganization in breast cancer cells","volume":"7","author":"Xiang","year":"2016","journal-title":"Oncotarget"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1248","article-title":"starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data","volume":"42","author":"Li","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"B27","doi-asserted-by":"publisher","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: an online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.jaci.2024.04.019","article-title":"ALOX15(+) M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps","volume":"154","author":"Liu","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-023-08976-y","article-title":"Diverse endotypes of chronic rhinosinusitis and clinical implications","volume":"65","author":"Xie","year":"2023","journal-title":"Clin Rev Allergy Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-023-01190-8","article-title":"E3 ubiquitin ligase NEDD4L inhibits epithelial-mesenchymal transition by suppressing the \u03b2-catenin\/HIF-1\u03b1 positive feedback loop in chronic rhinosinusitis with nasal polyps","volume":"45","author":"Chen","year":"2024","journal-title":"Acta Pharmacol Sin"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2021.11.05","article-title":"TGF-\u03b22-induced NEAT1 regulates lens epithelial cell proliferation, migration and EMT by the miR-26a-5p\/FANCE axis","volume":"14","author":"Yu","year":"2021","journal-title":"Int J Ophthalmol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2023.69.10.27","article-title":"Long non-coding RNA NEAT1 inhibits high glucose-induced EMT and renal fibrogenesis in Human Embryonic Kidney 293 cells via regulating miR-204\/SOX4 axis","volume":"69","author":"Ahmad Wadaan","year":"2023","journal-title":"Cell Mol Biol (Noisy-le-grand)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3892\/etm.2021.9798","article-title":"Knockdown of lncRNA NEAT1 expression inhibits cell migration, invasion and EMT by regulating the miR-24-3p\/LRG1 axis in retinoblastoma cells","volume":"21","author":"Luan","year":"2021","journal-title":"Exp Ther Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0327-8","article-title":"The p21-activated kinase 4-Slug transcription factor axis promotes epithelial-mesenchymal transition and worsens prognosis in prostate cancer","volume":"37","author":"Park","year":"2018","journal-title":"Oncogene"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2023.101544","article-title":"PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt\/\u03b2-catenin, p-ERK\/MAPK and p-AKT\/PI3K pathways","volume":"35","author":"Samant","year":"2023","journal-title":"Biochem Biophys Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"G490","DOI":"10.1152\/ajpgi.00229.2019","article-title":"Group II p21-activated kinase, PAK4, is needed for activation of focal adhesion kinases, MAPK, GSK3, and \u03b2-catenin in rat pancreatic acinar cells","volume":"318","author":"Ramos-\u00c1lvarez","year":"2020","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01430-1","article-title":"MicroRNA-199-3p up-regulation enhances chondrocyte proliferation and inhibits apoptosis in knee osteoarthritis via DNMT3A repression","volume":"70","author":"Gu","year":"2021","journal-title":"Inflammation Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1177\/09636897221108192","article-title":"MiR-199-3p suppressed inflammatory response by targeting MECP2 to alleviate TRX-induced PHN in mice","volume":"31","author":"Wang","year":"2022","journal-title":"Cell Transplant"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03068-3","article-title":"MUC1-C regulates NEAT1 lncRNA expression and paraspeckle formation in cancer progression","volume":"43","author":"Bhattacharya","year":"2024","journal-title":"Oncogene"},{"key":"B40","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13045-018-0656-7","article-title":"The lncRNA NEAT1 activates Wnt\/\u03b2-catenin signaling and promotes colorectal cancer progression via interacting with DDX5","volume":"11","author":"Zhang","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/s41419-020-03164-8","article-title":"LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness","volume":"11","author":"Zhu","year":"2020","journal-title":"Cell Death Dis"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1159\/000503976","article-title":"Interleukin-33 promotes th2\/th17 response in eosinophilic and non-eosinophilic nasal polyps","volume":"82","author":"Luo","year":"2020","journal-title":"ORL J Otorhinolaryngol Relat Spec"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/ACI.0000000000000588","article-title":"Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis","volume":"20","author":"Ryu","year":"2020","journal-title":"Curr Opin Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1613179\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T04:10:51Z","timestamp":1751256651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1613179\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2025.1613179"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1613179","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]},"article-number":"1613179"}}