MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway
Authors Xu H, Wu Y, Li L, Yuan W, Zhang D, Yan Q, Guo Z, Huang W
Received 23 August 2016
Accepted for publication 7 November 2016
Published 14 February 2017 Volume 2017:12 Pages 627—638
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 4
Editor who approved publication: Dr Richard Russell
Hong Xu,1–3,* Yuting Wu,2–4,* Li Li,1–3 Weifeng Yuan,1–3 Deming Zhang,2–4 Qitao Yan,2,3 Zhenhui Guo,2,3 Wenjie Huang1–3
1Department of Respiratory Medicine, 2Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support, 3Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support, 4Department of Geriatric Respiratory Medicine, General Hospital of Guangzhou Command of PLA, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Objectives: COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA). MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders. Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD.
Materials and methods: miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats. The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay. Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene. Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells. Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed.
Results: COPD rat model was successfully induced by smoke inhalation. Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene. In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2. In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition.
Conclusion: Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients.
Keywords: COPD, miR-344b-1-3p, TLR2, invasive pulmonary aspergillosis
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