ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1613179
LncRNA NEAT1 Promotes Epithelial-Mesenchymal Transition in Nasal Polyp Cells via the miR-199-3p/PAK4 Axis
Provisionally accepted
- 1First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 2Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
- 3Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Cancer Hospital, Chongqing University, Chongqing, China
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Background and Purpose: 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-mesenchymal transition (EMT) in CRSwNP, focusing on its regulatory interaction with the miR-199-3p/PAK4 axis.: 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. In vivo 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. Results: 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. Ecadherin 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. Conclusion: 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.
Keywords: CRSwNP, NEAT1, EMT, miR-199-3p, PAK4, non-coding RNA
Received: 16 Apr 2025; Accepted: 16 Jun 2025.
Copyright: © 2025 Li, Jiang, Zhang, Zheng, Yuan, Shen, Zhao, Lu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yi Zhao, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Cancer Hospital, Chongqing University, Chongqing, 400030, China
Tao Lu, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Yucheng Yang, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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