Circular RNA circPSEN1 promotes neovascularization by regulating the miR-150-5p/TRIM65 axis in diabetic retinopathy
TL;DR
Mechanistically, circPSEN1 acts as a sponge for miR-150-5p, enhancing TRIM65 expression and contributing to DR pathogenesis, indicating that circPSEN1 may serve as a therapeutic target for DR.
Abstract
Diabetic retinopathy (DR), a major microvascular complication of diabetes, is a leading cause of vision loss. Neovascularization is a hallmark of DR, and circRNA-PSEN1 (circPSEN1) has emerged as a key regulator in its development. However, the precise molecular mechanisms by which circPSEN1 contributes to DR remain unclear. This study investigates the role of circPSEN1 in DR, focusing on its interaction with miR-150-5p and TRIM65. Human retinal microvascular endothelial cells (hRMECs) were cultured under high-glucose (HG) conditions to establish an in vitro DR model, and streptozotocin-induced DR rats were used for in vivo analysis. Lentivirus-mediated gene modulation was employed to alter expression levels. Cell viability, migration, angiogenesis, and inflammatory cytokine release were assessed using CCK-8, transwell, tube formation assays, and ELISA. Dual-luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP) techniques were used to examine the interactions between circPSEN1, miR-150-5p, and TRIM65. Elevated circPSEN1 and TRIM65 levels, along with reduced miR-150-5p expression, were observed in retinal tissues from DR rats. In HG-stimulated hRMECs, circPSEN1 knockdown inhibited cell proliferation, migration, and angiogenesis, while reducing inflammatory cytokine release. These effects were reversed by miR-150-5p suppression or TRIM65 overexpression, suggesting a regulatory role of both molecules in DR. Mechanistically, circPSEN1 acts as a sponge for miR-150-5p, enhancing TRIM65 expression and contributing to DR pathogenesis. Our findings indicate that circPSEN1 may serve as a therapeutic target for DR.