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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作者:Yun Zhang, Lingyun Shao

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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