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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

ABSTRACT: Long-term high-fat diet feeding increases the circulating concentration of stearic acid (SA), which has a potent toxic effect on β-cells, but the underlying molecular mechanisms have not been fully elucidated. Here, we evaluated the role of lncRNA TCONS_00077866 (lncRNA-866) in SA-induced β-cell inflammation. lncRNA-866 was selected for study because it demonstrated the largest fold-difference in expression of five lncRNAs that were affected by SA treatment using lncRNA High-throughput Sequencing analysis. Knockdown of lncRNA-866 by virus-mediated shRNA expression in mice or Smart Silencer in β-TC6 cells significantly inhibited the SA-induced reduction in insulin secretion and β-cell inflammation. lncRNA-866 directly bound to miR-297b-5p, thereby preventing it from reducing the expression of its target serum amyloid A3 (SAA3), according to lncRNA-miRNA-mRNA co-expression network analysis and luciferase reporter assay. Furthermore, overexpression of miR-297b-5p or inhibition of SAA3 also had marked protective effects against the deleterious effects of SA in β-TC6 cells and mouse islets. In conclusion, lncRNA-866 silencing ameliorates SA-induced β-cell inflammation by targeting the miR-297b-5p/SAA3 axis. lncRNA-866 inhibition may represent a new strategy to protect β-cells against the effects of SA during the development of type 2 diabetes.

ORGANISM(S): Mus musculus

PROVIDER: GSE168825 | GEO | 2022/03/31

REPOSITORIES: GEO

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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

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