MiRNA-138-5p protects the early diabetic retinopathy by regulating NOVA1
1Department of Ophthalmology, Yiwu Central Hospital, Yiwu, China. caojuan_198106@163.com.
Objective:
To elucidate the function of miRNA-138-5p in the early diabetic retinopathy (DR) and the potential mechanism.
Materials And Methods:
DR model in rats was first established by streptozotocin (STZ) injection. MiRNA-138-5p expression in rat retinal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Besides, its expression in retinal capillary endothelial cells (EC) and pericytes (RP) was also detected. Cell counting kit-8 (CCK-8) assay was performed to evaluate proliferative potentials of EC and RP cells. The target gene of miRNA-138-5p was predicted by bioinformatics and further confirmed by dual-luciferase reporter gene assay. Rescue experiments were carried out to verify whether the target gene could reverse the regulatory effect of miRNA-138-5p on the proliferation of EC and RP cells.
Results:
MiRNA-138-5p was lowly expressed in retinal tissues of DR rats, as well as in EC and RP cells. Overexpression of miRNA-138-5p suppressed the proliferative rate of EC and RP cells, and miRNA-138-5p knockdown obtained the opposite trends. NOVA1 was verified to be the target gene of miRNA-138-5p by dual-luciferase reporter gene assay and RIP assay, which was highly expressed in retinal tissues of DR rats, EC, and RP cells. MiRNA-138-5p knockdown markedly upregulated the mRNA and protein levels of NOVA1 in EC and RP cells. Of note, the inhibitory effect of miRNA-138-5p overexpression on proliferative potentials of EC and RP cells was reversed by NOVA1 overexpression. On the contrary, miRNA-138-5p knockdown accelerated their proliferative potentials and was further reversed by NOVA1 knockdown.
Conclusions:
MiRNA-138-5p was lowly expressed in retinal tissues of DR rats, as well as in EC and RP cells. MiRNA-138-5p regulates the early DR by promoting cell proliferation via targeting NOVA1.
Insights
MicroRNA-138-5p is downregulated in diabetic retinopathy (DR). It regulates cell proliferation by targeting NOVA1, offering a potential therapeutic target for early DR.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a microvascular complication of diabetes.
- Early detection and intervention are crucial for managing DR.
- The role of microRNAs (miRNAs) in DR pathogenesis is an active area of research.
Purpose of the Study:
- To investigate the function of miRNA-138-5p in early diabetic retinopathy (DR).
- To elucidate the underlying molecular mechanism involving its target gene.
- To assess its potential as a biomarker or therapeutic target for DR.
Main Methods:
- Established a rat model of DR using streptozotocin (STZ).
- Quantified miRNA-138-5p expression in retinal tissues and cells (endothelial cells and pericytes) using qRT-PCR.
- Utilized bioinformatics and dual-luciferase reporter assays to identify and confirm NOVA1 as the target gene.
- Performed rescue experiments to validate the functional interaction.
Main Results:
- MiRNA-138-5p expression was significantly reduced in DR rat retinas and associated cells.
- Overexpression of miRNA-138-5p inhibited, while knockdown enhanced, the proliferation of retinal endothelial cells and pericytes.
- NOVA1 was confirmed as a direct target of miRNA-138-5p and was upregulated in DR.
- Modulating NOVA1 expression reversed the effects of miRNA-138-5p on cell proliferation.
Conclusions:
- MiRNA-138-5p is downregulated in early diabetic retinopathy.
- MiRNA-138-5p acts as a tumor suppressor by inhibiting cell proliferation via targeting NOVA1.
- This miRNA-138-5p/NOVA1 axis represents a potential therapeutic strategy for managing early DR.
