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Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps
Jianwei Zhang1, Lei Han2, Feng Chen3
1Department of Otolaryngology-Head and Neck Surgery, Shanghai Pudong New District Gongli Hospital/Second Military Medical University Affiliated Hospital, Shanghai, 200135, China.
Background:
Let-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP.
Methods:
The expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6.
Results:
Let-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP.
Conclusion:
We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.
Insights
Let-7a-5p is downregulated in chronic rhinosinusitis with nasal polyps (CRSwNP). This microRNA regulates inflammation via the IL-6/Ras-MAPK pathway in CRSwNP.
Area of Science:
- Molecular Biology
- Immunology
- Otolaryngology
Background:
- Let-7a-5p acts as a tumor suppressor in nasopharyngeal carcinoma.
- The role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) remains uninvestigated.
Purpose of the Study:
- To investigate the expression pattern of let-7a-5p in CRSwNP.
- To elucidate the functional role of let-7a-5p in CRSwNP pathogenesis.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) to assess let-7a-5p, TNF-α, IL-1β, and IL-6 expression.
- Western blot to analyze Ras-MAPK pathway protein levels.
- Dual luciferase reporter and RNA pull-down assays to confirm let-7a-5p and IL-6 interaction.
Main Results:
- Let-7a-5p was significantly downregulated in CRSwNP tissues and cells.
- Increased expression of TNF-α, IL-1β, and IL-6 observed in CRSwNP.
- Let-7a-5p mimic suppressed TNF-α, IL-1β, and IL-6 expression and inhibited the Ras-MAPK pathway.
- IL-6 identified as a direct target gene of let-7a-5p.
Conclusions:
- Let-7a-5p plays a crucial role in regulating inflammatory responses in CRSwNP.
- The let-7a-5p/IL-6 axis modulates the Ras-MAPK pathway in CRSwNP.
- Findings suggest let-7a-5p as a potential therapeutic target for CRSwNP.
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