LncRNA TUG1 regulates autophagy-mediated endothelial-mesenchymal transition of liver sinusoidal endothelial cells by sponging miR-142-3p.

Accumulating evidence indicates that competing endogenous RNA networks play a critical role in cirrhosis progression. However, their biological role and regulatory mechanisms in liver sinusoidal endothelial cells (LSECs) have not been explored. Here, we exposed LSECs to starvation and lipopolysaccharide (LPS) treatment and assessed changes in TUG1 and miR-142-3p expression, autophagy, and endothelial-mesenchymal transition (EndMT). We confirmed the effects of targeted binding between miR-142-3p and TUG1 or ATG5 by luciferase activity and radio-immunoprecipitation assay. Using an rat model of cirrhosis, we evaluated autophagy and EndMT in LSECs by immunofluorescence co-localization and immunohistochemical staining. The diagnostic efficiency of miR-142-3p and LPS were determined by receiver-operating characteristic curve analysis. We found that LSECs survived starvation by activating autophagy. LPS treatment enhanced autophagy and promoted EndMT of LSECs by upregulating TUG1. Our rat model of cirrhosis confirmed that serum LPS level, autophagy, and EndMT were increased in LSECs. TUG1 was highly expressed in LSECs, and TUG1 knockdown suppressed ATG5-mediated autophagy and EndMT of LSECs. TUG1 regulated ATG5 via shared miR-142-3p response elements. miR-142-3p was expressed at low levels in LSECs and negatively regulated autophagy and EndMT by reducing ATG5 expression. Our results suggest that TUG1 promotes LPS-induced autophagy and EndMT of LSECs by functioning as an endogenous sponge for miR-142-3p and promoting the expression of ATG5. LPS and miR-142-3p are potential diagnostic and therapeutic targets in cirrhosis.