Inhibition of Lncrna TCONS_00077866 Ameliorates the High Stearic Acid Diet-Induced Mouse Pancreatic Β-Cell Inflammatory Response by Increasing Mir-297B-5p to Downregulate SAA3 Expression.

Long-term consumption of a high-fat diet increases the circulating concentrationof stearic acid (SA), which has a potent toxic effect on β-cells, but the underlyingmolecular mechanisms of this action have not been fully elucidated. Here, we evaluatedthe role of lncRNA TCONS_00077866(lnc866) in SA-induced β-cell inflammation. lnc866 was selected forstudy because lncRNA high-throughputsequencing analysis demonstrated it to have the largest fold-difference in expression of five lncRNAs that were affected by SA treatment.Knockdown of lnc866 by virus-mediated shRNA expression in mice or by SmartSilencer in mouse pancreatic β-TC6 cells significantly inhibitedthe SA-induced reduction in insulin secretion and β-cell inflammation. According to lncRNA-microRNA (miRNAs)-mRNAco-expression network analysis and luciferase reporter assays, lnc866 directlybound to miR-297b-5p, thereby preventing it from reducing the expression of itstarget serum amyloid A3 (SAA3). Furthermore, overexpression of miR-297b-5p orinhibition of SAA3 also had marked protective effects against the deleterious effectsof SA in β-TC6 cells and mouse islets. In conclusion, lnc866 silencing amelioratesSA-induced β-cell inflammationby targeting the miR-297b-5p/SAA3 axis. lnc866 inhibition may represent a newstrategy to protect β-cells against the effects of SA during the development oftype 2 diabetes.