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.

中文翻译：

---

环状RNA-ZNF609通过充当miR-184的海绵来调节角膜新血管形成。

角膜新血管形成可导致异常的血管在正常透明和半透明的角膜中生长，从而导致各种威胁视力的眼部疾病。已知microRNA和环状RNA在众多生物学功能的调节中起着至关重要的作用。迫切需要了解miRNA和环状RNA在角膜新生血管形成中的分子机制。我们旨在阐明特定的环状RNA cZNF609在角膜新生血管形成中的作用。通过RT-qPCR确定cZNF609和miR-184水平。进行荧光素酶报告基因测定和RNA免疫沉淀测定以验证cZNF609的目标。通过体外细胞增殖，迁移和管形成测定以及体内角膜缝合模型评估了cZNF609和miR-184的生物学功能。在角膜新生血管形成过程中观察到cZNF609的上调和miR-184的下调。cZNF609充当miR-184海绵来阻止miR-184活性。miR-184的过表达抑制了HCEKs细胞的增殖，体外迁移和体内血管生成。可以通过重新引入cZNF609来挽救miR-184介导的抑制作用。在机械上，cZNF609 / miR-184相互作用调节下游的Akt和VEGF信号通路。cZNF609和miR-184的干预可作为病理性角膜新血管形成治疗的潜在策略。和体内血管生成。可以通过重新引入cZNF609来挽救miR-184介导的抑制作用。在机械上，cZNF609 / miR-184相互作用调节下游的Akt和VEGF信号通路。cZNF609和miR-184的干预可能是病理性角膜新血管形成治疗的潜在策略。和体内血管生成。可以通过重新引入cZNF609来挽救miR-184介导的抑制作用。在机械上，cZNF609 / miR-184相互作用调节下游的Akt和VEGF信号通路。cZNF609和miR-184的干预可作为病理性角膜新血管形成治疗的潜在策略。