AbstractBackgroundLet-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.MethodsThe 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.ResultsLet-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.ConclusionWe demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.

01 Apr 1996·Current Opinion in Cell Biology

Targeting signal transduction for disease therapy

Review

Author: Levitzki, A

With the advance in the molecular understanding of disease processes, it has been appreciated that many diseases result from the malfunctions of signaling pathways. This recognition has led to intensive research and the development of therapies based on the interception of cellular signaling in diseased cells. In the past two years, success has been achieved using a blocker of the farnesylation of Ras as a tumor inhibitor, a JAK-2 blocker as an efficient inhibitor of recurrent pre-B cell acute lymphoblastic leukemia, and a platelet-derived growth factor receptor kinase as a blocker of restenosis.

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Indication	Highest Phase	Country/Location	Organization	Date
Brain Cancer	Discovery	JP	Kidswell Bio Corp.	05 Jun 2024
Brain Cancer	Discovery	JP	Hamamatsu University School of Medicine	05 Jun 2024

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