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Abstract：
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.
CONCLUSIONS: We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway 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.
CONCLUSIONS: We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.
摘要：
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)中的作用尚未见报道.本研究旨在确定let-7a-5p在CRSwNP中的表达模式和作用。
方法：let-7a-5p的表达水平，TNF-α,IL-1β,通过RT-qPCR检测CRSwNP组织和细胞中的IL-6。进行Western印迹分析以测量Ras-MAPK途径的蛋白表达。使用双荧光素酶报告基因测定和RNA下拉测定来探索let-7a-5p与IL-6之间的关系。
结果：Let-7a-5p在CRSwNP组织和细胞中显著下调。此外，TNF-α的mRNA表达，IL-1β和IL-6在CRSwNP组织中增加，而let-7a-5p模拟物抑制TNF-α的表达，IL-1β和IL-6。除此之外,let-7a-5p与TNF-α呈负相关,CRSwNP组织中的IL-1β和IL-6。在我们的研究中,发现IL-6是let-7a-5p的靶基因。此外,let-7-5p模拟物明显降低了Ras的蛋白质水平，p-Raf1，p-MEK1和p-ERK1/2，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CRSwNP中的Ras-MAPK通路调节炎症反应。
方法：let-7a-5p的表达水平，TNF-α,IL-1β,通过RT-qPCR检测CRSwNP组织和细胞中的IL-6。进行Western印迹分析以测量Ras-MAPK途径的蛋白表达。使用双荧光素酶报告基因测定和RNA下拉测定来探索let-7a-5p与IL-6之间的关系。
结果：Let-7a-5p在CRSwNP组织和细胞中显著下调。此外，TNF-α的mRNA表达，IL-1β和IL-6在CRSwNP组织中增加，而let-7a-5p模拟物抑制TNF-α的表达，IL-1β和IL-6。除此之外,let-7a-5p与TNF-α呈负相关,CRSwNP组织中的IL-1β和IL-6。在我们的研究中,发现IL-6是let-7a-5p的靶基因。此外,let-7-5p模拟物明显降低了Ras的蛋白质水平，p-Raf1，p-MEK1和p-ERK1/2，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CRSwNP中的Ras-MAPK通路调节炎症反应。
