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Published on: May 21, 2018
Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps
1Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Background:
Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated.
Methods:
SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments.
Results:
In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375-3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3’-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity.
Conclusions:
MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.
Insights
Small extracellular vesicles (sEVs) from nasal polyps promote epithelial-mesenchymal transition (EMT) by delivering miR-375-3p, which targets QKI. This highlights sEVs and miR-375-3p as potential diagnostic and therapeutic targets for chronic rhinosinusitis with nasal polyps (CRSwNP).
Area of Science:
- Molecular Biology
- Cell Biology
- Otorhinolaryngology
Background:
- Epithelial-mesenchymal transition (EMT) is implicated in chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis.
- The role of small extracellular vesicles (sEVs) in CRSwNP-associated EMT remains under-investigated.
Purpose of the Study:
- To investigate the role of sEVs in promoting EMT in human nasal epithelial cells (hNECs).
- To identify specific microRNAs within sEVs that contribute to EMT in CRSwNP.
- To explore the potential of sEVs and associated microRNAs as diagnostic or therapeutic targets for CRSwNP.
Main Methods:
- Isolation of sEVs from nasal mucosa using ultracentrifugation.
- MicroRNA sequencing and RT-qPCR to analyze differential microRNA expression in sEVs.
- Assessment of EMT induction in hNECs by sEVs and specific microRNAs, including target gene identification (QKI) for miR-375-3p using dual-luciferase reporter assays.
Main Results:
- sEVs derived from eosinophilic CRSwNP (ENP-sEVs) induced EMT in hNECs, correlating with increased EMT markers.
- MiR-375-3p was significantly elevated in ENP-sEVs and directly targeted QKI, promoting EMT.
- The abundance of miR-375-3p in sEVs correlated with CRSwNP clinical symptom scores and disease severity.
Conclusions:
- MiR-375-3p-enriched sEVs promote EMT in hNECs by suppressing QKI, contributing to CRSwNP.
- MiR-375-3p within sEVs shows potential as a diagnostic biomarker for CRSwNP severity.
- Targeting miR-375-3p and sEVs offers a promising avenue for innovative CRSwNP management strategies.
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