Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2023; 14(3): 209-221
Published online Mar 15, 2023. doi: 10.4239/wjd.v14.i3.209
miR-124 is upregulated in diabetic mice and inhibits proliferation and promotes apoptosis of high-glucose-induced β-cells by targeting EZH2
Xiao-Kai Duan, Yong-Xiang Sun, Hong-Yun Wang, Yan-Yan Xu, Shi-Zhen Fan, Jin-Ya Tian, Yong Yu, Yan-Yun Zhao, Yan-Li Jiang
Xiao-Kai Duan, Yong-Xiang Sun, Hong-Yun Wang, Yan-Yan Xu, Shi-Zhen Fan, Jin-Ya Tian, Yong Yu, Yan-Yun Zhao, Yan-Li Jiang, Department of General Practice, Zhengzhou First People’s Hospital, Zhengzhou 450000, Henan Province, China
Author contributions: Duan XK, Sun YX and Wang HY designed and coordinated the study; Xu YY, Fan SZ and Tian JY performed the experiments, acquired and analyzed data; Duan XK, Sun YX, YU Y, Zhao YY and Jiang YL interpreted the data and wrote the manuscript; All authors approved the final version of the article.
Supported by The Medical Science and Technology Key Project of Henan Province, No. 2018020733.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Zhengzhou First People’s Hospital (Approval No. 202004008).
Institutional animal care and use committee statement: All animal experiments in this study were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978). All examination procedures were meet the ethical standards formulated by institutional review board of Zhengzhou First People’s Hospital.
Conflict-of-interest statement: All authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Kai Duan, Doctor, MMed, Chief Physician, Department of General Practice, Zhengzhou First People’s Hospital, No. 56 Dongdajie Street, Zhengzhou 450000, Henan Province, China. medicalworkers@126.com
Received: August 17, 2022
Peer-review started: August 17, 2022
First decision: December 12, 2022
Revised: January 5, 2023
Accepted: February 15, 2023
Article in press: February 15, 2023
Published online: March 15, 2023
Processing time: 210 Days and 10.4 Hours
ARTICLE HIGHLIGHTS
Research background

Diabetes is a metabolic disorder disease characterized by chronic hyperglycemia. The pathological features of diabetes include insulin resistance and a secretory deficiency in pancreatic islets β-cell. In clinical studies, a variety of miRNA are involved in the occurrence and development of diabetes. And miR-124 is highly expressed in the serum of patients with diabetes and in pancreatic islet β-cells. So, the role and mechanism of action of miR-124 in diabetes was explored in the diabetes mellitus type 2 (T2DM) mice and high glucose (HG) -induced Min6 cells.

Research motivation

A variety of miRNAs were abnormally expressed in patients with diabetes and affected insulin secretion by regulating the differentiation of islet β-cells, or affecting insulin synthesis and secretion. So, what is the role and mechanism of miR-124 in diabetes.

Research objectives

The present study aimed to investigate the expression of miR-124 in diabetic mice and the potential mechanism of action in islet β-cells.

Research methods

Mice were fed with a high sucrose/high-fat diet combined with a low-dose streptozotocin injection to establish the mouse model of T2DM. The expression levels of miR-124 and enhancer of zeste homolog 2 (EZH2) in pancreatic tissues of diabetic mice were detected. The targeted relationship between miR-124 and EZH2 was predicted by Targetscan software and verified by a double luciferase reporter assay. To model diabetic mouse islets β-cells, Min6 cells were grown in HG medium to mimic glucolipotoxicity. The insulin secretion, proliferation, cell cycle and apoptosis of HG-induced Min6 cells were detected after interference of miR-124a and/or EZH2.

Research results

The expression of miR-124 was upregulated and EZH2 was downregulated in the pancreatic tissue of diabetic mice compared with control mice, and the expression of miR-124 was negatively correlated with that of EZH2. miR-124 was highly expressed in HG-induced Min6 cells. Inhibition of miR-124 promoted insulin secretion and cell proliferation, induced the transition from the G0/G1 phase to the S phase of the cell cycle, and inhibited cell apoptosis in HG-induced Min6 cells. EZH2 was one of the targets of miR-124. Co-transfection of miR-124 inhibitor and siRNA-EZH2 could reverse the effects of the miR-124 inhibitor in HG-induced Min6 cells.

Research conclusions

miR-124 is highly expressed in diabetic mice and HG-induced Min6 cells and regulates insulin secretion, proliferation and apoptosis of islet β-cells by targeting EZH2.

Research perspectives

miR-124-EZH2 axis might be one of the pathogenesis mechanisms of diabetes, providing a new target for the treatment of diabetes.