CircRNA SCMH1 regulates the miR-200a-3p/ZEB1 signaling axis to promote diabetes-induced retinal epithelial-mesenchymal transition.

ABSTRACT

Diabetic retinopathy (DR) is one of the common systemic complications of diabetes. Epithelial-mesenchymal transition (EMT) is required for DR progression. Previous studies have explored that circular RNAs (circRNAs) are crucial for DR development. Herein, we focused on the biological functions of circSCMH1 in DR. RT-qPCR determined the expression of circSCMH1, miR-200a-3p and ZEB1. EMT-related proteins were measured by Western blot. Gene combinations were validated by RIP and dual luciferase reporter assays. CCK-8, EdU, TUNEL staining and Transwell analysis were used to assess the cellular function. FISH analysis assessed the localization of circSCMH1 and miR-200a-3p. HE staining was used to detect retinal structures in a mouse DR model. High-glucose (HG) significantly increased circSCMH1 expression in ARPE-19 cells. Additionally, circSCMH1 silencing repressed proliferation, migration, and EMT in HG cells. Mechanistically, circSCMH1 positively regulated ZEB1 expression via targeting miR-200a-3p. Furthermore, circSCMH1 was observed to induce HG cell growth and EMT by regulating the miR-200a-3p/ZEB1 axis. Finally, we verified that downregulation of circSCMH1 or ZEB1 alleviated EMT in the retina of diabetic mice. These findings have implications for new therapeutic targets for DR.