Introduction
The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of diabetic retinopathy (DR). This study investigated the effects of circular RNA ZNF532 (circZNF532) on apoptosis and pyroptosis of RPE cells.
Materials and Methods
Blood samples were collected from patients with DR and healthy volunteers. A human RPE cell line ARPE‐19 was induced by high glucose (HG) and assayed for cell viability, apoptosis, and pyroptosis. The binding of miR‐20b‐5p with circZNF532 and STAT3 was confirmed by a luciferase activity assay. A mouse model of diabetic retinopathy was established.
Results
CircZNF532 and STAT3 were upregulated but miR‐20b‐5p was downregulated in the serum samples of patients with DR and HG‐induced ARPE‐19 cells. Elevated miR‐20b‐5p or CircZNF532 knockdown enhanced proliferation but reduced apoptosis and pyroptosis of ARPE‐19 cells. CircZNF532 sponged miR‐20b‐5p and inhibited its expression. STAT3 was verified as a target of miR‐20b‐5p. MiR‐20b‐5p modulated ARPE‐19 cell viability, apoptosis, and pyroptosis by targeting STAT3. Mice with STZ‐induced diabetes showed elevated expressions of circZNF532 and STAT3 but decreased the level of miR‐20b‐5p compared with the controls. Knockdown of circZNF532 inhibited apoptosis and pyroptosis in mouse retinal tissues.
Conclusion
CircZNF532 knockdown rescued human RPE cells from HG‐induced apoptosis and pyroptosis by regulating STAT3 via miR‐20b‐5p.
Background: Age-related macular degeneration (AMD) is the leading cause of blindness for people over 50 years old worldwide. The purpose of this study was to identify differentially expressed and methylated genes (DEMGs) and construct a co-expression network for AMD.Methods: Microarray expression (GSE29801 dataset) and DNA methylation (GSE102952 dataset) profiles were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were analyzed between AMD retina tissues and normal retina tissues. A protein-protein interaction (PPI) network was constructed and hub genes were screened, followed by functional enrichment analysis. Then, weighted gene co-expression network analysis (WGCNA) was conducted.The ARPE-19 cells were maintained in a hypoxic state to construct an AMD cellular model. Enzyme-linked immunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation.Results: After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and upregulated genes were identified for extramacular AMD. A total of 4 hub genes (LMNB2, EMD, HLA-A, and HLA-B) were screened for AMD in the extramacular retina. Furthermore, 13 hypermethylated and downregulated genes and 31 hypomethylated and up-regulated genes were identified for macular AMD. Among them, 11 hub genes (HLA-A,
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