Int J Med Sci 2019; 16(10):1356-1365. doi:10.7150/ijms.35149 This issue

Research Paper

Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice

Manjing Cao1,2, Lusi Zhang1,2, Jiang-Hui Wang3,4, Huilan Zeng1,2, Yingqian Peng1,2, Jingling Zou1,2, Jingming Shi1,2, Liwei Zhang1,2, Yun Li1,2, Shigeo Yoshida5, Luosheng Tang1,2, Yedi Zhou1,2 ✉

1. Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
2. Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, China
3. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
4. Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
5. Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan

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Cao M, Zhang L, Wang JH, Zeng H, Peng Y, Zou J, Shi J, Zhang L, Li Y, Yoshida S, Tang L, Zhou Y. Identifying circRNA-associated-ceRNA networks in retinal neovascularization in mice. Int J Med Sci 2019; 16(10):1356-1365. doi:10.7150/ijms.35149. Available from

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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.

Keywords: circular RNA (circRNA), expression profile, microarray, oxygen-induced retinopathy, retinal neovascularization