IntroductionIncreasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4+ T cells from patients with rheumatoid arthritis (RA).MethodsThe expression profile of miRNAs in CD4+ T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.ResultsmiRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4+ T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-α), and in vitro studies showed TNF-α upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.ConclusionsWe have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-α levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets.

Key Points miR-146a may be involved in the pathogenesis of ALPS by targeting Fas. Sustained expression of miR-146a in B cells is the major factor leading to the enhanced homeostatic expansion of B and T cells.

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Pneumonia is a common respiratory disease worldwide, which is preventable and treatable; however, it is recognized as a leading cause of mortality in children. The present study aimed to investigate the role and mechanism of microRNA (miR)‑20a in inflammation in pediatric pneumonia. Clinical serum samples were collected from children with pneumonia and healthy children. Initially, the serum expression levels of miR‑20a were detected by reverse transcription‑quantitative polymerase chain reaction. Subsequently, A549 cells were randomly divided into four groups: Control group; lipopolysaccharide (LPS; 1 µg/ml) group; LPS + miR‑20a group; and LPS + miR‑20a + pyrrolidine dithiocarbamate (PDTC; 100 mmol/l) group. The concentrations of interleukin‑6 (IL‑6), tumor necrosis factor (TNF)‑α and C‑reactive protein (CRP) in clinical serum samples and A549 cells were determined by ELISA. In addition, the protein expression levels of inhibitor of nuclear factor (NF)‑κB α (IκBα) and phosphorylated (p)‑NF‑κB were measured by western blotting. The results demonstrated that miR‑20a was upregulated in children with pneumonia and in lung cells with LPS‑induced inflammatory injury (P<0.01). In addition, compared with the LPS group, cells in the LPS + miR‑20a group exhibited increased expression levels of IL‑6, TNF‑α and CRP (P<0.05). Overexpression of miR‑20a also resulted in upregulation of the expression levels of IκBα and p‑NF‑κB compared with in the LPS group (P<0.05). Furthermore, treatment with the NF‑κB inhibitor PDTC inhibited the expression of inflammatory factors compared with in the LPS + miR‑20a group (P<0.05). In conclusion, the present study indicated that miR‑20a is upregulated in pediatric pneumonia, and overexpression of miR‑20a may promote inflammation through activation of the NF‑κB signaling pathway.