Department of Ophthalmology, Huai'an Second People' and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
Department of Ophthalmology, Huai'an Second People' and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
Gene. 2020 Jul 15;747:144654. doi: 10.1016/j.gene.2020.144654. Epub 2020 Apr 4.
Diabetic retinopathy (DR)is a common diabetes complication, resulting in the loss of vision. circRNAshave been reported to serve as ceRNA via targeting corresponding miRNAs and modulating mRNA expression in various diseases. Recently, increasing reports has indicated circRNAs can exert a significant role inDR progression. However, the expression and mechanism of hsa_circ_0041795 in human retinal pigment epithelial cells ARPE-19 treated by high glucose remains poorly known. Hence, we aimed to work figure out the effect of hsa_circ_0041795 in high glucose (HG)-induced ARPE-19 cell damage and study its molecular mechanisms. In our current research, we found that hsa_circ_0041795 was obviously up-regulated in HG-treated ARPE-19 cells. High dose of glucose greatly depressed ARPE-19 cell survival and contributed to cell apoptosis. In addition, we observed that loss of hsa_circ_0041795 enhanced cell proliferation and inhibit ARPE-19 cell apoptosis, after HG incubation. Furthermore, data of ELISA indicated that hsa_circ_0041795 siRNA significantly restrained inflammatory factors expression, such as TNF-α, IL-1β and IL-6 in ARPE-19 cells treated with HG. miR-646 has been recognized in multiple diseases and currently, we predicted that miR-646 acted as a target of hsa_circ_0041795. Moreover, we found that miR-646 inhibitors dramatically reversed the effect of hsa_circ_0041795 siRNA on ARPE-19 cells. Additionally, a dual-luciferase reporter assay proved that VEGFC was a direct target of miR-646. Our results demonstrated that hsa_circ_0041795 might exhibit a novel therapeutic potential in the treatment of DR.
糖尿病性视网膜病变（DR）是一种常见的糖尿病并发症，可导致视力丧失。 circRNA 已被报道可通过靶向相应的 miRNA 并调节各种疾病中的 mRNA 表达来作为 ceRNA。最近，越来越多的报道表明 circRNA 在 DR 进展中发挥重要作用。然而， hsa_circ_0041795 在高糖（HG）处理的人视网膜色素上皮细胞 ARPE-19 中的表达和机制仍知之甚少。因此，我们旨在研究 hsa_circ_0041795 在高糖诱导的 ARPE-19 细胞损伤中的作用及其分子机制。在我们的研究中，我们发现 hsa_circ_0041795 在 HG 处理的 ARPE-19 细胞中明显上调。高剂量的葡萄糖大大抑制了 ARPE-19 细胞的存活，并促进了细胞凋亡。此外，我们观察到在 HG 孵育后， hsa_circ_0041795 的缺失增强了 ARPE-19 细胞的增殖并抑制了细胞凋亡。此外，ELISA 数据表明， hsa_circ_0041795 siRNA 显著抑制了 HG 处理的 ARPE-19 细胞中炎症因子的表达，如 TNF-α、IL-1β 和 IL-6。miR-646 在多种疾病中已得到认可，目前我们预测 miR-646 是 hsa_circ_0041795 的一个靶点。此外，我们发现 miR-646 抑制剂可显著逆转 hsa_circ_0041795 siRNA 对 ARPE-19 细胞的作用。此外，双荧光素酶报告基因实验证实 VEGFC 是 miR-646 的直接靶标。我们的研究结果表明， hsa_circ_0041795 在 DR 的治疗中可能具有新的治疗潜力。
