Circular RNA-ZNF609 regulates corneal neovascularization by acting as a sponge of miR-184

Abstract

Corneal neovascularization can cause abnormal blood vessels to grow in the normally transparent and translucent cornea leading to various sight-threatening eye diseases. microRNAs and circular RNAs are known to play essential roles in the regulation of numerous biological functions. It is urgently needed to understand the molecular mechanism of miRNAs and circular RNAs in the corneal neovascularization. We aimed to elucidate the role of a specific a circular RNA, cZNF609, in the corneal neovascularization. cZNF609 and miR-184 levels were determined by RT-qPCR. Luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the target of cZNF609. The biological function of cZNF609 and miR-184 were assessed via cell proliferation, migration, and tube formation assays in vitro as well as the corneal suture model in vivo. The up-regulation of cZNF609 and down-regulation of miR-184 were observed during corneal neovascularization. cZNF609 acted as a miR-184 sponge to block miR-184 activity. Overexpression of miR-184 suppressed HCEKs cell proliferation, migration in vitro, and angiogenesis in vivo. The miR-184-mediated inhibition effect can be rescued through the re-introduction of cZNF609. Mechanically, cZNF609/miR-184 interaction regulated the downstream Akt and VEGF signaling pathway. Intervention of cZNF609 and miR-184 may serve as a potential strategy for pathological corneal neovascularization treatment.

Keywords: Circular RNAs; Cornea; Neovascularization; cZNF609; miR-184; microRNA.