miRNA-19a-3p Exacerbates Tube Formation by Targeting SOCS1 to Regulate JAK2/STAT3/VEGF in Diabetic Retinopathy.

Objective: Diabetic retinopathy (DR) is a retinal microangiopathy caused by diabetes mellitus. miRNAs have been shown to be involved in DR-associated micro vessel formation, influence the DR progression, and may be a therapeutic strategy for DR. miRNA-19a-3p is highly expressed in the vitreous of DR patients, however, its mechanism in the occurrence and development of DR is unclear. Therefore, the purpose of this study was to explore the potential mechanism of miRNA-19a-3p in the occurrence and development of DR.

Methods: Human retinal microvascular endothelial cells (hRMECs) were treated with 30 mM high glucose for 48 h to construct a DR cell model. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of miR-19a-3p and SOCS1; the cell viability was measured by Cell Counting Kit-8 after the interference or overexpression of miR-19a-3p. Cell scratch assay was used to verify the cell migration ability; tube formation assay to measure the tube formation ability. The targeting relationship between miR-19a-3p and SOCS1 was demonstrated by dual-luciferase reporter gene assay. Western blot was adopted to determine the protein expression levels of FGF2, VEGFA, SOCS1, JAK2, p-JAK2, STAT3, and p-STAT3.

Results: In the hRMECs induced by high glucose, miRNA-19a-3p was increased, while the expression level of SOCS1 was significantly decreased. The cell viability, migration, and tube formation could be markedly inhibited by suppressing the miR-19a-3p expression in hRMECs under high glucose conditions. Besides, the expression level of SOCS1 was remarkably elevated after the inhibition of miR-19a-3p expression. In addition, miR-19a-3p could directly target the negatively regulated SOCS1. The inhibition of SOCS1 expression reversed the effects of miR-19a-3p down-regulation on the viability, migration, and tube formation of hRMECs under high glucose conditions. miR-19a-3p could activate the JAK2/STAT3 signaling pathway by inhibiting the expression of SOCS1, thereby promoting the tube formation.

Conclusion: miRNA-19a-3p can target SOCS1 to regulate JAK2/STAT3/VEGF, thereby exacerbating tube formation in DR. The results of this study provide a new target for the treatment of DR.