The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
Cornea. 2019 Nov;38(11):1443-1449. doi: 10.1097/ICO.0000000000002089.
To identify differentially expressed circular RNAs (circRNAs) in corneal neovascularization.
We established an alkali burn-induced corneal neovascularization model and performed circRNA expression profiling to identify differentially expressed circRNAs between avascular corneas and vascularized corneas. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses of the host genes of dysregulated circRNAs were performed to determine the related biological modules and pathological pathways. Real-time polymerase chain reactions were performed to detect the expression pattern of circRNAs in the clinical samples. In vitro experiments were performed to determine the role of circRNAs in vascular endothelial angiogenic effects.
Two hundred twenty-nine circRNAs were differentially expressed between avascular corneas and vascularized corneas. The host genes of dysregulated circRNAs were targeted to cell cycle (biologic process), cytoplasm (cellular component), and protein binding (molecular function). Rap1 signaling was identified as the most enriched signaling pathway. Clinical studies showed that the human ortholog of cZFP609 and cKifap3 was dysregulated in the vascularized human corneas. cKifap3 silencing facilitated vascular endothelial angiogenic effects by regulating endothelial cell proliferation, migration, and tube formation.
This study suggests that circRNAs are involved in the pathogenesis of corneal neovascularization. cZFP609 and cKifap3 may serve as promising targets for the treatment of corneal neovascularization.
鉴定角膜新生血管化过程中差异表达的环状 RNA（circRNA）。
我们建立了碱烧伤诱导的角膜新生血管化模型，并进行 circRNA 表达谱分析，以鉴定无血管角膜和血管化角膜之间差异表达的 circRNA。对失调 circRNA 的宿主基因进行基因本体富集和京都基因与基因组百科全书分析，以确定相关的生物学模块和病理途径。通过实时聚合酶链反应检测临床样本中 circRNA 的表达模式。进行体外实验以确定 circRNA 在血管内皮血管生成效应中的作用。
在无血管角膜和血管化角膜之间有 229 个 circRNA 差异表达。失调 circRNA 的宿主基因靶向细胞周期（生物学过程）、细胞质（细胞成分）和蛋白结合（分子功能）。Rap1 信号通路被鉴定为最富集的信号通路。临床研究表明，cZFP609 和 cKifap3 的人同源物在血管化的人角膜中失调。cKifap3 沉默通过调节内皮细胞增殖、迁移和管形成促进血管内皮血管生成效应。
本研究表明 circRNA 参与了角膜新生血管化的发病机制。cZFP609 和 cKifap3 可能成为治疗角膜新生血管化的有前途的靶点。
