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Published on: December 30, 2025
MicroRNA-411 plays a protective role in diabetic retinopathy through targeted regulating Robo4
1Department of Ophthalmology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, China. hukai70@163.com.
Objective:
The aim of this study was to explore the role of microRNA-411 in diabetic retinopathy (DR) and to further understand its mechanism of action.
Materials And Methods:
A rat model of diabetes (20 in the DM group) and a normal control group (20 in the control group) was established. The changes in blood glucose and body weight were compared between the two groups. At the same time, the expression changes in microRNA-411 and Roundabout 4 (ROBO4) in the two groups of rats were detected. The biological prediction of the potential binding sites of ROBO4 and microRNA-411 was verified by the Dual-Luciferase reporter gene assay, and the regulatory relationship of microRNA-411 to ROBO4 was verified in human retinal pigment epithelial cells (ARPE-19). Meanwhile, we investigated the effects of high glucose and hypoxia on the viability of ARPE-19 cells and explored whether microRNA-411 has a regulatory role in the effects. Finally, a cell reverse experiment was designed to verify whether microRNA-411 functions through ROBO4.
Results:
Compared with the NC group, the blood glucose of the DM group was significantly increased while the body weight was reduced. In addition, the expression level of microRNA-411 was markedly decreased in diabetic rats, and the mRNA and protein levels of ROBO4 were notably increased, which were all dependent on time. Biological prediction revealed that ROBO4 might be a potential target gene of microRNA-411, and the results of the Dual-Luciferase reporter gene assay confirmed that there is a binding relationship between them; meanwhile, microRNA-411 was proved to be able to inhibit the expression level of ROBO4 in vivo and in vitro. Both high glucose and hypoxia could inhibit the proliferation of ARPE-19 cells and increase the monolayer permeability. Additionally, up-regulation of microRNA-411 or down-regulation of ROBO4 could partially reverse this phenomenon. Cell reverse experiment showed that overexpression of ROBO4 partially reversed the protective effect of microRNA-411 on DR.
Conclusions:
MicroRNA-411 was down-regulated in the rat model of diabetic retinopathy and played a protective role in this disease, which might be achieved by negatively regulating the expression level of ROBO4.
Insights
MicroRNA-411 is decreased in diabetic retinopathy (DR) and protects against the disease. It achieves this by negatively regulating Roundabout 4 (ROBO4) expression, offering a potential therapeutic target for DR.
Area of Science:
- Ophthalmology
- Molecular Biology
- Endocrinology
Background:
- Diabetic retinopathy (DR) is a microvascular complication of diabetes.
- Understanding the molecular mechanisms underlying DR is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA-411 in a rat model of diabetic retinopathy.
- To elucidate the mechanism by which microRNA-411 influences DR, focusing on its interaction with Roundabout 4 (ROBO4).
Main Methods:
- Established a rat model of diabetes and compared it to a control group.
- Measured blood glucose, body weight, and expression levels of microRNA-411 and ROBO4.
- Utilized Dual-Luciferase reporter gene assay and human retinal pigment epithelial cells (ARPE-19) to verify the microRNA-411 and ROBO4 interaction.
- Investigated the effects of high glucose and hypoxia on ARPE-19 cells and the role of microRNA-411.
Main Results:
- Diabetic rats showed increased blood glucose, decreased body weight, reduced microRNA-411, and increased ROBO4 expression.
- Confirmed a direct binding relationship between microRNA-411 and ROBO4, with microRNA-411 inhibiting ROBO4 expression.
- High glucose and hypoxia impaired ARPE-19 cell viability and increased permeability, effects partially reversed by up-regulating microRNA-411 or down-regulating ROBO4.
Conclusions:
- MicroRNA-411 is significantly down-regulated in diabetic retinopathy.
- MicroRNA-411 exerts a protective effect in DR, likely by negatively regulating ROBO4.
- Targeting the microRNA-411/ROBO4 pathway may represent a novel therapeutic strategy for diabetic retinopathy.
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