Type 2 Diabetes

TCONS_00077866[LncRNA]

miR-297b-5p[miRNA]

SAA3[mRNA]

Mouse Pancreatic B-Tc6 Cells

Mus musculus (mouse)

Diabetes. 2021 Jul 14:db201079. doi: 10.2337/db20-1079.

Inhibition of lncRNA TCONS_00077866 ameliorates the high stearic acid diet-induced mouse pancreatic b-cell inflammatory response by increasing miR-297b-5p to downregulate SAA3 expression.

Luciferase reporter assay;

Long-term consumption of a high-fat diet increases the circulating concentration of stearic acid (SA), which has a potent toxic effect on b-cells, but the underlying molecular mechanisms of this action have not been fully elucidated. Here, we evaluated the role of lncRNA TCONS_00077866 (lnc866) in SA-induced b-cell inflammation. lnc866 was selected for study because lncRNA high-throughput sequencing 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 Smart Silencer in mouse pancreatic b-TC6 cells significantly inhibited the SA-induced reduction in insulin secretion and b-cell inflammation. According to lncRNA-microRNA (miRNAs)-mRNA co-expression network analysis and luciferase reporter assays, lnc866 directly bound to miR-297b-5p, thereby preventing it from reducing the expression of its target serum amyloid A3 (SAA3). Furthermore, overexpression of miR-297b-5p or inhibition of SAA3 also had marked protective effects against the deleterious effects of SA in b-TC6 cells and mouse islets. In conclusion, lnc866 silencing ameliorates SA-induced b-cell inflammation by targeting the miR-297b-5p/SAA3 axis. lnc866 inhibition may represent a new strategy to protect b-cells against the effects of SA during the development of type 2 diabetes.