Theranostics 2017; 7(11):2863-2877. doi:10.7150/thno.19353

Research Paper

Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction

Chang Liu1, 2*, Mu-Di Yao2, 3*, Chao-Peng Li4*, Kun Shan 1*, Hong Yang2, 3, Jia-Jian Wang1, Ban Liu5, Xiu-Miao Li3, Jin Yao2, 3, Qin Jiang2, 3✉, Biao Yan1, 6, 7✉

1. Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China;
2. The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China;
3. Eye Hospital, Nanjing Medical University, Nanjing, China;
4. Department of Ophthalmology, Huai'an First People's Hospital, Nanjing Medical University, Jiangsu, China;
5. Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China;
6. Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China;
7. State Key Laboratory of Molecular Engineering of Polymers (Fudan University), Shanghai, China.
* These authors contributed equally to this work.


Vascular dysfunction is a hallmark of ischemic, cancer, and inflammatory diseases, contributing to disease progression. Circular RNAs (circRNAs) are endogenous non-coding RNAs, which have been reported to be abnormally expressed in many human diseases. In this study, we used retinal vasculature to determine the role of circular RNA in vascular dysfunction. We revealed that cZNF609 was significantly up-regulated upon high glucose and hypoxia stress in vivo and in vitro. cZNF609 silencing decreased retinal vessel loss and suppressed pathological angiogenesis in vivo. cZNF609 silencing increased endothelial cell migration and tube formation, and protected endothelial cell against oxidative stress and hypoxia stress in vitro. By contrast, transgenic overexpression of cZNF609 showed an opposite effects. cZNF609 acted as an endogenous miR-615-5p sponge to sequester and inhibit miR-615-5p activity, which led to increased MEF2A expression. MEF2A overexpression could rescue cZNF609 silencing-mediated effects on endothelial cell migration, tube formation, and apoptosis. Moreover, dysregulated cZNF609 expression was detected in the clinical samples of the patients with diabetes, hypertension, and coronary artery disease. Intervention of cZNF609 expression is promising therapy for vascular dysfunction.

Keywords: vascular dysfunction, circular RNAs, microRNA sponge, retinopathy of prematurity, diabetic retinopathy.

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How to cite this article:
Liu C, Yao MD, Li CP, Shan K, Yang H, Wang JJ, Liu B, Li XM, Yao J, Jiang Q, Yan B. Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction. Theranostics 2017; 7(11):2863-2877. doi:10.7150/thno.19353. Available from