title: MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway.
abstract: OBJECTIVE
  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.
  
  
  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 andTLR2gene 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 ofTLR2gene. 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 targetingTLR2gene. 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.
  
  
  CONCLUSIONS
  Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator ofTLR2gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients.
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support; Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support; Department of Geriatric Respiratory Medicine, General Hospital of Guangzhou Command of PLA, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support; Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support; Department of Geriatric Respiratory Medicine, General Hospital of Guangzhou Command of PLA, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Deming
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support; Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support.
authors.forename: Qitao
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support; Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D019295:Computational Biology; D030541:Databases, Genetic; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D055666:Lipopeptides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D055666:Lipopeptides; C000622020:MIRN344 microRNA, rat; D035683:MicroRNAs; C508075:Pam(3)CSK(4) peptide; D012906:Smoke; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: COPD; TLR2; invasive pulmonary aspergillosis; miR-344b-1-3p