hsa_circ_0007086竞争性结合miR-494-3p/miR-372-5p调控CASP1促进细胞焦亡参与早期糖尿病性视网膜病变的机制研究

糖尿病性视网膜病变（DR）严重危害视力，课题组前期利用hRMECs构建早期DR细胞模型，证实焦亡具有重要作用，但circRNA在其中的功能尚未见报道。申请人通过芯片分析得到circRNA表达谱；进一步实验表明，敲低hsa_circ_0007086后，CASP1表达降低，焦亡减弱；又经ceRNA分析发现，hsa_circ_0007086通过结合miR-494-3p、miR-372-5p调控CASP1；据此提出hsa_circ_0007086竞争性结合miR-494-3p、miR-372-5p靶向CASP1调控早期DR焦亡的科学假说。本项目将利用早期DR细胞和动物模型，通过报告基因、RIP、RNA pull down等技术，在分子、细胞和动物等多个水平探索该信号轴的作用及分子机制；并利用临床样本进一步阐明该信号轴与DR的临床相关性。本项目将拓展人们对DR发病机制的认识，为早期防治提供实验依据。

Diabetic retinopathy (DR) seriously impairs vision. In previous experiments, our group used human retinal microvascular endothelial cells (hRMECs) to construct an early DR cell model, which confirmed that pyroptosis has an important role, but the regulatory function of circular RNA (circRNA) has not been reported. Our team analyzed the differential expression profiles of circRNA by microarray. Further experiments showed that after knocking down hsa_circ_0007086, the expression of CASP1 was decreased and the level of pyroptosis was weakened. Furthermore, we found that hsa_circ_0007086 may regulate CASP1 by binding miR-494-3p and miR-372-5p basing on ceRNA interaction analysis. Given this, we proposed the scientific hypothesis that hsa_circ_0007086 may promote pyroptosis in early DR by competitively binding miR-494-3p/miR-372-5p to target CASP1. This project will use early DR cell and animal models to explore the role and molecular mechanism of this signal axis at molecular, cellular and animal levels using luciferase reporter gene, RIP, RNA pull down and other technologies. Besides, clinical samples will be applied to further elucidate the clinical relevance of the signal axis and DR. This project will broaden our understanding of the pathogenesis of DR and provide experimental evidence for early prevention and treatment.