lncRNA GAS5-mediated miR-23a-3p promotes inflammation and cell apoptosis by targeting TLR4 in a cell model of sepsis

Abstract

Sepsis is a syndrome characterized by organ dysfunction and an abnormal immune response to infection. A growing body of research has shown the importance of long non-coding RNAs (lncRNAs) in tumorigenesis, virus replica- tion, inflammatory injury and other pathological processes. The aim of the present study was to explore the role and potential mechanism of the lncRNA growth arrest-specific 5 (GAS5) in the lipopolysaccharide (LPS)-induced inflammation and apop- tosis of THP-1 cells. An in vitro sepsis model was established by treating THP-1 cells with LPS. Apoptosis was detected by flow cytometry. The expression levels of IL-6, IL-1β and TNF-α were detected using reverse transcription-quantitative PCR (RT-qPCR) and ELISA, and those of GAS5, microRNA (miR)-23a-3p and Toll-like receptor 4 (TLR4) were detected by RT-qPCR. The changes in the biological activity of THP-1 cells induced by the silencing of GAS5 and overexpression of miR-23a-3p and TLR4 were investigated. The relation- ships among GAS5, miR-23a-3p and TLR4 were analyzed using luciferase reporter assays. The results revealed that LPS increased the expression of GAS5 in THP-1 cells, and GAS5 knockdown effectively inhibited inflammation and cell apoptosis in the LPS-induced sepsis model. In addi- tion, the results of the luciferase reporter assays indicated that both GAS5 and TLR4 directly target miR-23a-3p. The expression of miR-23a-3p was downregulated whereas that of TLR4 was upregulated in the septic cells. Further experi- ments showed that the overexpression of TLR4 attenuated the suppressive effects of miR-23a-3p overexpression and GAS5 knockdown on LPS-induced inflammation and apoptosis. In conclusion, the present study indicates that GAS5 strengthens LPS-induced inflammation and apoptosis via the miR-23a-3p/ TLR4 pathway.