Decreased microRNA-140-5p contributes to respiratory syncytial virus disease through targeting Toll-like receptor 4

microRNA-140-5p 减少通过靶向 Toll 样受体 4 导致呼吸道合胞病毒疾病

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Abstract

The abnormal expression of miRNAs (miRs) has previously been reported in respiratory syncytial virus (RSV) disease. However, to the best of our knowledge, the expression of miR-140-5p in patients with an RSV infection has never been explored. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the level of miR-140-5p in the blood and nasopharyngeal airway samples. ELISAs were performed to determine the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-8. A dual luciferase reporter assay was also performed to investigate the possible target gene of miR-140-5p. The results demonstrated that the levels of miR-140-5p were significantly decreased in the nasal mucosal and peripheral blood samples of patients with RSV infection. It was also revealed that overexpression of miR-140-5p decreased the inflammatory responses, while inhibition of miR-140-5p enhanced the inflammatory responses. Additionally, three binding sites of miR-140-5p in the 3untranslated region (UTR) of Toll-like receptor (TLR)4 were identified and a dual luciferase reporter assay demonstrated that miR-140-5p significantly suppressed the relative luciferase activity of pmirGLO-TLR4-3UTR. Furthermore, the level of miR-140-5p was shown to be increased following interferon (IFN)α incubation. Notably, inhibition of miR-140-5p markedly attenuated IFNα-mediated downregulation of tumor necrosis factor α, and interleukin-1β, -6 and -8 in BEAS-2B cells. In summary, decreased miR-140-5p levels are involved in RSV-infection diseases primarily through targeting TLR4.

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