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The T1D-associated lncRNA <i>Lnc13</i> modulates human pancreatic β cell inflammation by allele-specific stabilization of <i>STAT1</i> mRNA

Itziar González‐Moro, Ane Olazagoitia‐Garmendia, Máikel L. Colli, Nadia Cobo‐Vuilleumier, Thomas S. Postler, Lorella Marselli, Piero Marchetti, Sankar Ghosh, Benoit R. Gauthier, Décio L. Eizirik, Ainara Castellanos–Rubio, Izortze Santín

2020Proceedings of the National Academy of Sciences58 citationsDOIOpen Access PDF

Abstract

Significance The mechanisms by which autoimmunity is triggered/amplified in T1D remain to be clarified, and the lack of this basic understanding hampers efforts to prevent or arrest the disease. Testing the hypothesis that T1D-associated genetic variants in lncRNAs affect important pathways that modify inflammation and pancreatic β-cell survival will increase our understanding of T1D pathogenesis. In the present paper, we describe a molecular mechanism by which the T1D-associated lncRNA Lnc13 regulates pancreatic β-cell inflammation. These findings provide information on the molecular mechanisms by which disease-associated SNPs in lncRNAs influence disease pathogenesis and open the door for the development of novel diagnostic and therapeutic approaches based on lncRNA targeting.

Topics & Concepts

BiologySTAT1PathogenesisProinflammatory cytokineSingle-nucleotide polymorphismPancreatic isletsGenotypeGene knockdownChemokineAlleleInflammationNodGeneMolecular biologyGeneticsImmunologyIsletDiabetes mellitusEndocrinologyCancer-related molecular mechanisms researchRNA modifications and cancerImmune Cell Function and Interaction