bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023‒02‒05
one paper selected by
Thomas Farid Martínez
University of California, Irvine

  1. Biochem Biophys Res Commun. 2023 Jan 03. pii: S0006-291X(23)00010-4. [Epub ahead of print]647 62-71
      BACKGROUND: Dysfunction of pancreatic β-cells induced by glucocorticoids contributes to diabetes mellitus 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 β-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 β-cell dysfunction were evaluated by examining cell viability, apoptosis, insulin secretion, and reactive oxygen species (ROS) generation.
    RESULTS: DEX induced β-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 β-TC6 cells and attenuated DEX-induced dysfunction in β-TC6 cells. Moreover, transduced TAT-MIR7-3HG-ORF reversed DEX-mediated inhibition 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 β-TC6 cell dysfunction.
    CONCLUSION: The lncRNA MIR7-3HG encodes a short peptide, which can protect pancreatic β-cells from DEX-induced dysfunction by activating the PI3K/AKT pathway. Our study broadens the diversity and breadth of lncRNAs in human disorders.
    Keywords:  Glucocorticoids; MIR7-3HG ORF; PI3K/AKT pathway; Short peptide; β-TC6 cell dysfunction