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

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 pep...

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Published in:Biochemical and biophysical research communications 2023-03, Vol.647, p.62-71
Main Authors: Mao, Xiaoming, Zhou, Jinliang, Kong, Limin, Zhu, Li, Yang, Desheng, Zhang, Zhiyu
Format: Article
Language:English
Subjects:
Apoptosis - genetics
Dexamethasone - adverse effects
Glucocorticoids
Humans
Insulin-Secreting Cells - drug effects
MicroRNAs - genetics
MicroRNAs - pharmacology
MIR7-3HG ORF
Peptides - pharmacology
Phosphatidylinositol 3-Kinases - metabolism
PI3K/AKT pathway
Proto-Oncogene Proteins c-akt - metabolism
Reactive Oxygen Species - metabolism
RNA, Long Noncoding - metabolism
Short peptide
Signal Transduction
β-TC6 cell dysfunction
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Summary: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. 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. 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. 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. •LncRNA MIR7-3HG ORF encodes a 125-amino-acid-long peptide.•TAT-MIR7-3HG-ORF can transduce into β-TC6 cells.•TAT-MIR7-3HG-ORF abates DEX-induced β-TC6 cell dysfunction.•The PI3K/AKT pathway is involved in the regulation of TAT-MIR7-3HG-ORF.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2023.01.004