Let-7a-5p 调控鼻息肉慢性鼻窦炎的炎症反应。
Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps.
机构信息
Department of Otolaryngology-Head and Neck Surgery, Shanghai Pudong New District Gongli Hospital/Second Military Medical University Affiliated Hospital, Shanghai, 200135, China.
Department of Otolaryngology-Head and Neck Surgery, Suqian First People's Hospital, The Suqian Clinical college of Xuzhou Medical University, Suqian, 223800, Jiangsu Province, China.
出版信息
Diagn Pathol. 2021 Mar 30;16(1):27. doi: 10.1186/s13000-021-01089-0.
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.
背景
Let-7a-5p 被证明是鼻咽癌的肿瘤抑制剂。然而，let-7a-5p 在慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）中的作用尚未报道。本研究旨在确定 let-7a-5p 在 CRSwNP 中的表达模式和作用。
方法
通过 RT-qPCR 检测 CRSwNP 组织和细胞中 let-7a-5p、TNF-α、IL-1β 和 IL-6 的表达水平。Western blot 检测 Ras-MAPK 通路的蛋白表达。双荧光素酶报告基因检测和 RNA 下拉实验探讨 let-7a-5p 与 IL-6 的关系。
结果
Let-7a-5p 在 CRSwNP 组织和细胞中表达明显下调。此外，CRSwNP 组织中 TNF-α、IL-1β 和 IL-6 的 mRNA 表达增加，而 let-7a-5p 模拟物抑制了 TNF-α、IL-1β 和 IL-6 的表达。此外，let-7a-5p 与 CRSwNP 组织中的 TNF-α、IL-1β 和 IL-6 呈负相关。在本研究中，发现 IL-6 是 let-7a-5p 的靶基因。此外，let-7a-5p 模拟物明显降低了 Ras、p-Raf1、p-MEK1 和 p-ERK1/2 的蛋白水平，而 IL-6 过表达破坏了 let-7a-5p 对 CRSwNP 中 Ras-MAPK 通路的抑制作用。
结论
我们证明了 let-7a-5p/IL-6 相互作用通过 Ras-MAPK 通路调节 CRSwNP 中的炎症反应。
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