Silencing of lncRNA PVT1 ameliorates streptozotocin-induced pancreatic [beta] cell injury and enhances insulin secretory capacity by regulating miR-181a-5p

• Published in: Canadian journal of physiology and pharmacology Vol. 99; no. 3; pp. 303 - 312
• Main Authors: Cheng, Yinqin, Hu, Qiaosheng, Zhou, Jie
• Format: Journal Article
• Language: English
• Published: NRC Research Press 01.03.2021
• Subjects: Analysis; Apoptosis; Gene silencing; Identification and classification; Pancreatic beta cells; RNA; Streptozocin; China
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2020-0268

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 PVT-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 miR181a-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 [beta] cells by regulating miR-181a-5p, suggesting a promising biomarker in DM diagnosis and treatment.