Silencing of lncRNA PVT1 ameliorates streptozotocin-induced pancreatic ß cell injury and enhances insulin secretory capacity by regulating miR-181a-5p.
Can J Physiol Pharmacol
; 99(3): 303-312, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-32758099
ABSTRACT
Diabetes mellitus (DM) is a type of metabolic disorder characterized by long-term hyperglycemia. Accumulating evidence shows that long noncoding RNAs (lncRNAs) play significant roles in the occurrence and development of DM. This study intended to investigate the role of lncRNA plasmacytoma variant translocation 1 (PVT1) in rat insulinoma (INS-1) cells damaged by streptozotocin (STZ) and to identify the potential mechanisms. Firstly, PVT1 expression in INS-1 cells was assessed using RT-qPCR after STZ stimulation. After PVT1-knockdown, cell apoptosis, the contents of oxidative stress related markers, and changes in insulin secretion were detected. Results indicated that PVT1 was remarkably upregulated after STZ stimulation. PVT1-knockdown inhibited STZ-induced oxidative stress and apoptosis of INS-1 cells. Moreover, the insulin secretory capacity was notably elevated following PVT1 silencing. Subsequently, a luciferase reporter assay verified that miR-181a-5p was directly targeted by PVT1. The rescue assays revealed that miR-181a-5p inhibitor dramatically abrogated the effects of PVT1 silencing on oxidative stress, apoptosis, and insulin secretion. Taken together, these findings demonstrated that PVT1-knockdown could ameliorate STZ-induced oxidative stress and apoptosis and elevate insulin secretory capacity in pancreatic ß cells by regulating miR-181a-5p, suggesting a promising biomarker in DM diagnosis and treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
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MicroRNAs
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Diabetes Mellitus Experimental
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Células Secretoras de Insulina
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RNA Longo não Codificante
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Secreção de Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China