CircSLC16A12 Absence Inhibits High Glucose-Induced Dysfunction in Retinal Microvascular Endothelial Cells through Mediating miR-140-3p/FGF2 Axis in Diabetic Retinopathy

Abstract

Purpose

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus which can cause irreversible visual impairment and blindness. We intended to investigate the function of circular RNA (circRNA) solute carrier family 16 member 12 (SLC16A12) in DR progression.

Methods

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were applied to measure RNA and protein expression. Cell apoptosis was analyzed by flow cytometry (FCM) analysis. The angiogenesis ability was assessed by tube formation assay. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the release of inflammatory cytokines. Cell oxidative stress status was evaluated using commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay were conducted to confirm the intermolecular interactions.

Results

CircSLC16A12 level was enhanced in the serum samples of DR patients and high glucose (HG)-treated HRECs. CircSLC16A12 absence protected HRECs from HG-induced apoptosis, blood-retinal barrier (BRB) injury, tube formation, inflammatory response, and oxidative stress. CircSLC16A12 acted as a sponge for microRNA-140-3p (miR-140-3p), and circSLC16A12 knockdown-mediated effects were largely reversed by the absence of miR-140-3p in HRECs under HG condition. miR-140-3p interacted with the 3’ untranslated region (3’UTR) of fibroblast growth factor 2 (FGF2), and the overexpression of FGF2 largely overturned miR-140-3p overexpression-mediated effects in HRECs. CircSLC16A12 interference reduced the expression of FGF2 by up-regulating miR-140-3p in HRECs.

Conclusion

CircSLC16A12 silencing suppressed HG-induced dysfunction in HRECs partly by targeting miR-140-3p/FGF2 axis.

Keywords:

• Diabetic retinopathy
• high glucose
• retinal microvascular endothelial cells
• circSLC16A12
• miR-140-3p
• FGF2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.