# LncRNA NEAT1 promotes epithelial–mesenchymal transition in nasal polyp cells via the miR-199-3p/PAK4 axis

## TL;DR

This study shows that the long non-coding RNA NEAT1 helps nasal polyp cells change into a more mobile form, which could lead to new treatments for chronic sinusitis.

## Contribution

The novel finding is that NEAT1 promotes EMT in nasal polyps via the miR-199-3p/PAK4 regulatory axis.

## Key findings

- NEAT1 knockdown reduced cell migration and reversed EMT-related cytoskeletal changes.
- NEAT1 sponges miR-199-3p to upregulate PAK4, promoting EMT in nasal polyp cells.
- miR-199-3p overexpression suppressed PAK4 and mitigated NEAT1-induced EMT effects.

## Abstract

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.

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.

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.