Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice
Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice
复制标题
识别小鼠视网膜新生血管中的 circRNA 相关 ceRNA 网络。
DOI：
10.7150/ijms.35149
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发表时间：
2019-01-01
影响因子：
3.6
通讯作者：
Zhou, Yedi
中科院分区：
文献类型：
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作者：
Cao, Manjing;Zhang, Lusi;Zhou, Yedi
视网膜新生血管形成是一种严重导致人类视力丧失的并发症。研究表明，环状rna （circRNAs）在基因调控中发挥着重要作用。然而，circRNA在视网膜新生血管疾病中的表达谱和潜在机制尚不清楚。在本研究中，我们通过微阵列分析在氧诱导视网膜病变（OIR）小鼠模型的视网膜中发现了改变的环状rna。微阵列分析显示，与对照组相比，OIR视网膜中的539个环状rna发生了显著改变。其中，共鉴定出185个上调环状rna和354个下调环状rna。通过定量实时逆转录-聚合酶链反应（qRT-PCR）验证mmu_circRNA_002573、mmu_circRNA_011180、mmu_circRNA_016108和mmu_circRNA_22546这4种改变的circRNAs的表达水平。对已验证的环状RNA进行生物信息学分析，如竞争性内源性RNA （ceRNA）调控网络和基因本体（GO）富集分析表明，qRT-PCR验证的环状RNA与细胞过程、细胞部分和磷酸酯水解酶活性相关。京都基因与基因组百科（KEGG）通路分析表明，MAPK信号通路和肾素-血管紧张素系统与验证的环状rna相关，提示这些通路可能参与病理性血管生成。这些结果共同表明circRNAs在OIR视网膜中异常表达，并可能在视网膜新生血管疾病中发挥潜在作用。
Retinal neovascularization is a complication which caused human vision loss severely. It has been shown that circular RNAs (circRNAs) play essential roles in gene regulation. However, circRNA expression profile and the underlying mechanisms in retinal neovascular diseases remain unclear. In the present study, we identified altered circRNAs in the retinas of oxygen-induced retinopathy (OIR) mouse model by microarray profiling. Microarray analysis revealed that 539 circRNAs were significantly altered in OIR retinas compared with controls. Among them, 185 up-regulated and 354 down-regulated circRNAs were identified. The expression levels of 4 altered circRNAs including mmu_circRNA_002573, mmu_circRNA_011180, mmu_circRNA_016108 and mmu_circRNA_22546 were validated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatic analysis with validated circRNAs such as competing endogenous RNA (ceRNA) regulatory networks with Gene Ontology (GO) enrichment analysis demonstrated that qRT-PCR validated circRNAs were associated with cellular process, cell part and phosphoric ester hydrolase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that MAPK signaling pathway and renin-angiotensin system were related to validated circRNAs, suggesting these pathways may participate in pathological angiogenesis. The results together suggested that circRNAs were aberrantly expressed in OIR retinas and may play potential roles in retinal neovascular diseases.