miR-204 Targets PERK and Regulates UPR Signaling and β-Cell Apoptosis

Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of diabetes and the associated β-cell apoptosis. Although microRNAs (miRNAs) have been widely studied in various diseases including diabetes, the role of miRNAs in ER stress and β-cell apoptosis has only started to be elucidated. We recently showed that diabetes increases β-cell miR-204 and have now discovered that miR-204 directly targets the 3′untranslated region of protein kinase R-like ER kinase (PERK), 1 of the 3 ER transmembrane sensors and a key factor of the unfolded protein response (UPR). In addition, by using primary human islets, mouse islets, and INS-1 β-cells, we found that miR-204 decreased PERK expression as well as its downstream factors, activating transcription factor 4 and CCAAT enhancer-binding protein homologous protein, whereas it had no effect on the other 2 ER transmembrane sensors, activating transcription factor 6 and inositol-requiring enzyme-1α. Interestingly, we discovered that miR-204 also inhibite...