Inhibition of hsa_circ_0002570 suppresses high-glucose–induced angiogenesis and inflammation in retinal microvascular endothelial cells through miR-1243/angiomotin axis

• Published in: Cell stress & chaperones 2020-09, Vol.25 (5), p.767-777
• Main Authors: Liu, Guodan, Zhou, Shifeng, Li, Xinge, Ding, Xuchen, Tian, Miao
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiomotins; Assaying; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blindness; Cancer Research; Cell Biology; Cell Line; Cell proliferation; Cholecystokinin; Circular RNA; Diabetes mellitus; Diabetic retinopathy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Gene expression; Glucose; Humans; Immunology; Intercellular Signaling Peptides and Proteins - metabolism; Microfilament Proteins - metabolism; MicroRNAs - metabolism; Microvasculature; miRNA; mRNA; Neovascularization, Pathologic; Neurosciences; ORIGINAL PAPER; Polymerase chain reaction; Retina; Retinopathy; Ribonucleic acid; RNA; RNA, Circular - metabolism
• ISSN: 1355-8145; 1466-1268
• DOI: 10.1007/s12192-020-01111-2

Diabetic retinopathy (DR) is the most severe microvascular complication of diabetes and a major cause of visual impairment and blindness. However, the treatment for DR is still limited. Our study aimed to explore the role of circular RNA_0002570 in DR. First, we predicted the potential microRNA and mRNA that could bind to circ_0002570 and identified the miR-1243 and angiomotin gene; then, we used RT-PCR and Western blot to measure their expression. Next, we evaluated the abilities of proliferation, migration, and angiogenesis in vitro in human retinal microvascular endothelial cells (hRMECs) by CCK-8, transwell assay, and tube formation assay, respectively. To analyze the relationship among miR-1243, circ_0002570, and angiomotin, RNA pull-down and luciferase assay were performed. Our results showed that, in DR patients and high-glucose–induced hRMECs, miR-1243, circ_0002570, and angiomotin were all abnormally expressed. MiR-1243 could directly and competitively bind to both circ_0002570 and angiomotin mRNA to inhibit their expression. Moreover, circ_0002570 suppressed the abilities of proliferation, migration, and angiogenesis in hRMECs induced by high glucose, which was dependent on miR-1243-angiomotin axis. Furthermore, circ_0002570 could upregulate angiomotin by targeting miR-1243 to mediate the dysfunction of hRMECs induced by high glucose. In conclusion, circ_0002570 might serve as a potential target for diagnosis and treatment for DR.