TUG1 Represses Apoptosis, Autophagy, and Inflammatory Response by Regulating miR-27a-3p/SLIT2 in Lipopolysaccharide-Treated Vascular Endothelial Cells.

BACKGROUND:The dysfunction of vascular endothelial cells is associated with sepsis development. Long noncoding RNAs take part in the regulation of vascular endothelial cell function. This study aimed to explore the role and mechanism of long noncoding RNA taurine-upregulated gene 1 (TUG1) in lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS:LPS-treated human umbilical vein endothelial cells (HUVECs) were used as a model of sepsis in vitro. Quantitative real-time polymerase chain reaction was performed to detect the expression of TUG1, microRNA-27a-3p (miR-27a-3p) and slit guidance ligand 2 (SLIT2) messenger RNA. Western blot was conducted to measure the protein levels of SLIT2 as well as those involved in apoptosis, autophagy, and inflammatory response. Flow cytometry was used to detect cell apoptotic rate. The targets of TUG1 and miR-27a-3p were predicted via starBase (http://starbase.sysu.edu.cn/index.php). Dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays were carried out to validate the target correlation between miR-27a-3p and TUG1/SLIT2. RESULTS:TUG1 expression was decreased after the treatment of LPS in HUVECs. Overexpression of TUG1 decreased LPS-induced apoptosis, autophagy, and inflammatory response. TUG1 was a sponge of miR-27a-3p. Upregulation of miR-27a-3p reversed the suppressive effect of TUG1 overexpression on LPS-induced apoptosis, autophagy, and inflammatory response. SLIT2 was a target of miR-27a-3p. Knockdown of miR-27a-3p could inhibit LPS-induced injury by increasing SLIT2 in HUVECs. TUG1 could enhance SLIT2 expression by competitively sponging miR-27a-3p. CONCLUSIONS:TUG1 could repress cell apoptosis, autophagy, and inflammatory response in LPS-treated HUVECs by sponging miR-27a-3p to target SLIT2, providing a potential target for the treatment of sepsis.

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