Suppression of TRIM8 by microRNA-182-5p restricts tumor necrosis factor-α-induced proliferation and migration of airway smooth muscle cells through inactivation of NF-Κb.

Abstract

MicroRNAs (miRNAs) have emerged as critical modulators involved in the regulation of airway remodeling in asthma. MicroRNA-182-5p (miR-182-5p) has been reported as a key miRNA in regulating the proliferation and migration of various cell types, and its dysfunction contributes is implicated in a wide range of pathological processes. Yet, it remains unknown whether miR-182-5p modulates the proliferation and migration of airway smooth muscle (ASM) cells during asthma. In the present study, we aimed to determine the potential role of miR-182-5p in regulating the proliferation and migration of ASM cells induced by tumor necrosis factor (TNF)-α in vitro. We found that TNF-α stimulation markedly reduced miR-182-5p expression in ASM cells. Gain-of-function experiments showed that miR-182-5p upregulation suppressed the proliferation and migration of ASM cells induced by TNF-α. By contrast, miR-182-5p inhibition had the opposite effect. Notably, tripartite motif 8 (TRIM8) was identified as a target gene of miR-182-5p. TRIM8 expression was induced by TNF-α stimulation, and TRIM8 knockdown markedly impeded TNF-α-induced ASM cell proliferation and migration. Moreover, miR-182-5p overexpression or TRIM8 knockdown significantly downregulated the activation of nuclear factor-κB (NF-κB) induced by TNF-α. However, TRIM8 restoration partially reversed the miR-182-5p-mediated inhibitory effect on TNF-α-induced ASM cell proliferation and migration. In conclusion, our study indicates that miR-182-5p restricts TNF-α-induced ASM cell proliferation and migration through downregulation of NF-κB activation via targeting TRIM8. The results of our study highlight the potential importance of the miR-182-5p/TRIM8/NF-κB axis in the airway remodeling of asthma.

• Authors: Xiaomin Dang, Beibei He, Qian Ning, Ya Liu, Ying Chang, Mingwei Chen
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 83 Pg. 106475 (Jun 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32283508 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Carrier Proteins
• MicroRNAs
• Mirn182 microRNA, human
• NF-kappa B
• Nerve Tissue Proteins
• RNA, Small Interfering
• TRIM8 protein, human
• Tumor Necrosis Factor-alpha

Topics

• Airway Remodeling
• Asthma (metabolism)
• Carrier Proteins (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Gene Expression Regulation
• Humans
• MicroRNAs (genetics)
• Myocytes, Smooth Muscle (physiology)
• NF-kappa B (metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Respiratory System (pathology)
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)