Long noncoding RNA MALAT1 regulates sepsis in patients with burns by modulating miR‑214 with TLR5.

Abstract

The present study aimed to identify the involvement of the dysregulation of the metastasis‑associated lung adenocarcinoma transcript‑1 (MALAT1)/microRNA (miR)‑214/Toll‑like receptor (TLR)5 signaling pathway in the development of post‑burn sepsis. THP‑1 cells were used in the present study, in addition to 8‑10 week‑old mice. ELISA analysis was performed to examine the expression levels of inflammation‑associated factors. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis and western blotting were performed to analyze the influence of burns or burns with infection on the production of MALAT1, miR‑214 and TLR5. Commonly‑used software and a luciferase assay was used to confirm the target gene of miR‑214. RT‑qPCR analysis and western blotting were performed to elucidate the effects of lipopolysaccharide (LPS), miR‑214 and MALAT1 on the expression of miR‑214, TLR5, tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑10. Burn injury increased TLR5, TNF‑α, IL‑6 and IL‑10 expression levels, which were abolished by treatment with MALAT1. miR‑214 directly targeted TLR5 by binding to the TLR5 3' untranslated region (ITR), and the luciferase activity of the wild‑type, and not the mutant, TLR5 3'UTR was reduced following transfection with miR‑214. In cells not treated with LPS, MALAT1 and anti‑miR‑214 significantly enhanced TLR5, TNF‑α, IL‑6 and IL‑10 expression, and repressed miR‑214 production; whereas, miR‑214 and MALAT1 short hairpin (sh)RNA decreased TLR5, TNF‑α, IL‑6 and IL‑10 expression levels, and increased miR‑214 expression. In cells treated with LPS, LPS reduced miR‑214 expression and increased TLR5, TNF‑α, IL‑6 and IL‑10 expression compared with LPS‑untreated cells, and the effects of MALAT1, anti‑miR‑214, miR‑214 and MALAT1 shRNA on TLR5, TNF‑α, IL‑6 and IL‑10 were the same as in LPS‑untreated cell. The results of the present study indicated the association between the dysregulation of MALAT1/miR‑214/TLR5 and the risk of post‑burn sepsis.

• Authors: Fengying Gao, Rong Chen, Yaofeng Xi, Qiujian Zhao, Haifeng Gao
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 19 Issue 5 Pg. 3756-3766 (May 2019) ISSN: 1791-3004 [Electronic] Greece
• PMID: 30896848 (Publication Type: Journal Article)

Chemical References

• Malat1 long non-coding RNA, mouse
• MicroRNAs
• Mirn214 microRNA, mouse
• RNA, Long Noncoding
• Tlr5 protein, mouse
• Toll-Like Receptor 5

Topics

• Animals
• Burns (complications, genetics, metabolism)
• Disease Models, Animal
• Female
• Mice
• Mice, Inbred C57BL
• MicroRNAs (supply & distribution)
• RNA, Long Noncoding (genetics)
• Sepsis (etiology, metabolism, pathology)
• Signal Transduction
• Toll-Like Receptor 5 (genetics)