Department of Ophthalmology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Comput Math Methods Med. 2022 Aug 5;2022:8519664. doi: 10.1155/2022/8519664. eCollection 2022.
Circular RNAs (circRNAs) are involved in the pathogenesis of many diseases, and circ_0041795 was shown to promote the progression of diabetic retinopathy (DR). The aim of this study was to explore the molecular mechanism of circ_0041795 in DR.
Human retinal pigment epithelial cells ARPE-19 were treated with high glucose (HG). circ_0041795, miR-589-5p, and Yes-associated protein 1 (YAP1) levels were measured by reverse transcription-quantitative polymerase chain reaction assay. Biological behaviors were examined by Cell Counting Kit-8 assay for cell viability, EdU assay for cell proliferation, flow cytometry for cell apoptosis, and enzyme-linked immunosorbent assay for cell inflammation. Oxidative stress was assessed via the commercial kits. Western blot was performed for analysis of protein expression. The molecular binding was assessed via dual-luciferase reporter assay and pull-down assay.
HG-induced inhibiting effects on cell viability and proliferation but promoting effects on cell apoptosis, inflammation, and oxidative stress were ameliorated by silence of circ_0041795. circ_0041795 was identified to act as a miR-589-5p sponge. The regulation of circ_0041795 in HG-induced cell injury was achieved by inhibiting miR-589-5p. miR-589-5p targeted YAP1 and relieved HG-induced cell dysfunction via downregulating YAP1. circ_0041795 sponged miR-589-5p to regulate YAP1 level and activated the NF-B pathway through the miR-589-5p/YAP1 axis.
All these results elucidated that circ_0041795 facilitated the development of DR by inducing miR-589-5p-mediated YAP1 upregulation.
环状 RNA（circRNAs）参与多种疾病的发病机制，circ_0041795 被证明可促进糖尿病视网膜病变（DR）的进展。本研究旨在探讨 circ_0041795 在 DR 中的分子机制。
用高糖（HG）处理人视网膜色素上皮细胞 ARPE-19。采用逆转录定量聚合酶链反应检测 circ_0041795、miR-589-5p 和 Yes 相关蛋白 1（YAP1）水平。通过细胞计数试剂盒-8 检测细胞活力、EdU 检测细胞增殖、流式细胞术检测细胞凋亡和酶联免疫吸附试验检测细胞炎症，检测细胞的生物学行为。通过商业试剂盒评估氧化应激。通过 Western blot 分析蛋白表达。通过双荧光素酶报告基因检测和下拉实验评估分子结合。
沉默 circ_0041795 可改善 HG 诱导的细胞活力和增殖抑制作用，但促进细胞凋亡、炎症和氧化应激。circ_0041795 被鉴定为 miR-589-5p 的海绵体。circ_0041795 通过抑制 miR-589-5p 调节 HG 诱导的细胞损伤。miR-589-5p 靶向 YAP1，并通过下调 YAP1 缓解 HG 诱导的细胞功能障碍。circ_0041795 海绵 miR-589-5p 调节 YAP1 水平，并通过 miR-589-5p/YAP1 轴激活 NF-B 通路。
这些结果表明，circ_0041795 通过诱导 miR-589-5p 介导的 YAP1 上调促进 DR 的发展。
