miR-25 and miR-92b regulate insulin biosynthesis and pancreatic ß-cell apoptosis.
Endocrine
; 76(3): 526-535, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35194770
ABSTRACT
PURPOSE:
Pancreatic ß-cell failure is a central hallmark of the pathogenesis of diabetes mellitus; however, the molecular basis underlying chronic inflammation-caused ß-cell failure remains unclear. This study reported here specifically assessed the association between miR-25/miR-92b family and ß-cell failure in diabetes.METHODS:
IL-1ß and two additional ER stress activators, palmitate and tunicamycin were applied to evaluate the expression level miR-25 by Taqman® RT-PCR. Glucose- and potassium-stimulated insulin secretion assays were performed to assess ß-cell function. Dual-luciferase activity, and western blotting assays were utilized for miR-25 target gene verification. CCK-8 and TUNEL staining were used to evaluate ß-cell viability and apoptosis.RESULTS:
miRNA ChIP identified the increased level of miR-25 in INS-1 cells by IL-1ß treatment. Expression levels of miR-25 were significantly upregulated with the treatment of IL-1ß, palmitate or tunicamycin in both INS-1 cells and human islets. Ectopic elevation of miR-25 recapitulated most featured ß-cell defects caused by IL-1ß, including inhibition of insulin biosynthesis and increased ß-cell apoptosis. These detrimental effects of miR-25 relied on its seed sequence recognition and repressed expression of its target genes Neurod1 and Mcl1. The miR-25/NEUROD1 axis reduced insulin biosynthesis via transcriptional regulation of ß-cell specific genes. The miR-25/MCL1 axis caused ß-cell apoptosis in a CASPASE-3/PARP1-dependent manner. Comparable impairments were generated by miR-92b and miR-25, emphasizing the redundant biological roles of miRNA family members with the same seed sequence.CONCLUSION:
MiR-25/miR-92b family plays a major role in ß-cell failure occurring under inflammation and diabetes states.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células Secretoras de Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article