A peptide encoded by lncRNA MIR7-3 host gene (MIR7-3HG) alleviates dexamethasone-induced dysfunction in pancreatic fi-cells through the PI3K/AKT signaling pathway

Background: Dysfunction of pancreatic fi-cells induced by glucocorticoids contributes to diabetes mel-litus development. Long noncoding RNAs (lncRNAs) have been recognized to contain short open reading frames (ORFs) that can be translated into functional small peptides. Here, we investigated whether the short peptide encoded by the lncRNA MIR7-3 host gene (MIR7-3HG) can affect dexamethasone (DEX)-induced fi-cell dysfunction.Methods: Bioinformatics analysis was used for selection of MIR7-3HG and prediction of its protein encoding potential. The small peptide was identified by a western blot method. The cell-permeable TAT was fused into MIR7-3HG ORF to produce the cell-permeable fusion peptide (TAT-MIR7-3HG-ORF). The effects of TAT-MIR7-3HG-ORF on DEX-induced fi-cell dysfunction were evaluated by examining cell viability, apoptosis, insulin secretion, and reactive oxygen species (ROS) generation.Results: DEX induced fi-TC6 cell dysfunction by impairing cell viability, insulin secretion and promoting cell apoptosis and ROS generation. The MIR7-3HG ORF could encode a 125-amino-acid-long short peptide. TAT-MIR7-3HG-ORF effectively transduced into fi-TC6 cells and attenuated DEX-induced dysfunction in fi-TC6 cells. Moreover, transduced TAT-MIR7-3HG-ORF reversed DEX-mediated inhibi-tion of the activation of the PI3K/AKT signaling pathway. The inhibitor of the PI3K/AKT pathway partially abolished the alleviative effect of transduced TAT-MIR7-3HG-ORF on DEX-induced fi-TC6 cell dysfunction.Conclusion: The lncRNA MIR7-3HG encodes a short peptide, which can protect pancreatic fi-cells from DEX-induced dysfunction by activating the PI3K/AKT pathway. Our study broadens the diversity and breadth of lncRNAs in human disorders. (c) 2023 Elsevier Inc. All rights reserved.