Conclusions
MALAT1 promotes PDR by inhibiting miR126-5p and inducing REC proliferation, migration and angiogenesis.
Methods
Rat retinal endothelial cells (RECs) was induced with 30 mM glucose to build an in vitro PDR model. MALAT1 was down-regulated using siRNA sequences, and miR-126-5p was up-regulated with miRNA mimics. Dual-luciferase reporter assay and RNA immunoprecipitation assay were carried out to identify and validate the targeting relationship between MALAT1 and miR-126-5p. Angiogenesis, cell proliferation and cell migration were detected using tubule formation, CCK-8, and scratch assays, respectively. Western blots quantified angiogenesis- and migration-associated genes vascular endothelial growth factor (VEGF), MMP2 and MMP9, while qPCR measured MALAT1 and miR-126-5p levels.
Objective
Diabetic retinopathy (DR) is the primary reason for blindness among the middle-aged and elderly. It can progress to proliferative diabetic retinopathy (PDR), a condition that is accompanied by retinal neovascularization as the disease worsens. Understanding the pathogenesis of PDR can facilitate the development of treatments. In this study, we aimed to investigate the involvement in the lncRNA MALAT1 (MALAT1)/miR-126-5p axis in modulating PDR progression.
Results
In high-glucose induced RECs, MALAT1 was up-regulated while miR-126-5p was down-regulated. The angiogenesis as well as the proliferation and migration capacities of high glucose-induced RECs were suppressed when MALAT1 was down-regulated or miR-126-5p was up-regulated, accompanied by reductions in VEGF, MMP-2 and MMP9. RNA immunoprecipitation assay confirmed that miR-126-5p could be enriched in MALAT1 sequences. Dual-luciferase reporter assay confirmed the targeted inhibition of miR-126-5p by MALAT1. Downregulating miR-126-5p counteracted the effect of MALAT1 downregulation on RECs induced by high glucose. Conclusions: MALAT1 promotes PDR by inhibiting miR126-5p and inducing REC proliferation, migration and angiogenesis.