MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway.

Int J Chron Obstruct Pulmon Dis

Department of Respiratory Medicine; Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support; Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support.

Published: August 2017

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 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 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 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 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317246PMC
http://dx.doi.org/10.2147/COPD.S120415DOI Listing

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