4.6 Article

SNP rs322931 (C>T) in miR-181b and rs7158663 (G>A) in MEG3 aggravate the inflammatory response of anal abscess in patients with Crohn's disease

Journal

AGING-US
Volume 14, Issue 7, Pages 3313-3324

Publisher

IMPACT JOURNALS LLC

Keywords

anal abscess; inflammation; MEG3; miR-181b; TNF

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This study investigated the correlation between SNPs in the MEG3/miR-181b signaling pathway and the severity of anal abscess in patients with Crohn's disease. The results showed that two SNPs, rs322931 (C>T) in miR-181b and rs7158663 (G>A) in MEG3, could aggravate the inflammatory response and affect the MEG3/miR-181b/TNF-alpha signaling pathway in Crohn's disease patients with anal abscess.
Background: The MEG3/miR-181b signaling has been implicated in the pathogenesis of several diseases including Crohn's disease. This work aimed to study the correlation between SNPs in MEG3/miR-181b and the severity of anal abscess in patients with Crohn's disease. Methods: Quantitative real-time PCR was performed to analyze the expression of MEG3 and miR-181b. ELISA was carried out to examine the expression of TNF-alpha, IL-113, IL-6, CRP, SSA, AAT, AAG and HPT in the peripheral blood of patients with Crohn's disease. Luciferase assay was performed to explore the role of miR-181b in the expression of MEG3 and TNF-alpha. Results: The expression of MEG3 and miR-181b in the peripheral blood of patients with Crohn's disease was remarkably associated with the rs322931 and rs7158663 polymorphisms. rs322931 (C>T) in miR-181b and rs7158663 (G>A) in MEG3 significantly promoted the expression of TNF-alpha, IL-113, IL-6, CRP, SSA, AAT, AAG and HPT. Luciferase assay demonstrated that miR-181b was capable of repressing the expression of MEG3 and TNF alpha through binding to their specific binding sites. Moreover, alteration of MEG3 and miR-181b expression also showed a remarkable impact on the MEG3/miR-181b/TNF-alpha signaling pathway in THP-1 cells. Conclusions: In conclusion, our study demonstrated that two SNPs, rs322931 (C>T) in miR-181b and rs7158663 (G>A) in MEG3, could aggravate the inflammatory response of anal abscess in patients with Crohn's disease via modulating the MEG3/miR-181b/TNF-alpha signaling pathway.

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