Objective. To explore the changes of circRNAs in the retina of diabetic patients without diabetic retinopathy (DR) to screen latent protective factor. Methods. The sequencing data of the retina from three diabetic donors that possess no noticeable pathological feature of the retina at ultimate eye inspection and three healthy donative samples were involved in this study. Herein, we carried out bioinformatics analysis to disclose the expression pattern and characteristics of circRNAs on the basis of Gene Ontology as well as KEGG pathway analyses. Then, sequencing data were applied to infer the interaction between selected circRNAs and miR-204-5p. The potential miRNA response elements for the annotated circRNAs and their target gene were speculated using TargetScan as well as miRanda. Results. RNA sequencing detected 28,978 alternative circRNAs. Thereinto, 1063 were expressed with significant difference. circKMT2E was upregulated more than two folds in alloxan-induced diabetic retinal tissues compared with normal retinal tissues, exhibiting an expression trend opposite to miR-204-5p. Bioinformatics analysis showed that circKMT2E have four seed sequences on hsa-miR-204-5p. Thus, circKMT2E was speculated to have function on the basis of sponging miR-204-5p in order to participate in the pathogenetic process of DR. Besides, miR-204-5p was speculated to be able to bind SIRT1, which can interact with its target proteins, and adjusts various cell functions including cellular inflammatory responses, proliferation, as well as apoptosis. Conclusion. The upregulation of circKMT2E in the early stage of DR may be involved in its pathogenesis and may activate the SIRT1 signaling pathway to protect the retina by the sponge function to miR-204-5p.

中文翻译：

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circKMT2E 通过海绵 miR-204-5p 通过 SIRT1 信号通路保护视网膜免受早期糖尿病视网膜病变的影响


客观的。探讨无糖尿病视网膜病变（DR）的糖尿病患者视网膜中circRNA的变化，以筛选潜在的保护因子。方法。本研究涉及三名糖尿病供体的视网膜测序数据，这些供体在最终眼科检查时没有明显的视网膜病理特征，以及三名健康供体样本的视网膜测序数据。在此，我们在Gene Ontology和KEGG通路分析的基础上进行了生物信息学分析，揭示了circRNA的表达模式和特征。然后，应用测序数据来推断选定的 circRNA 和 miR-204-5p 之间的相互作用。使用 TargetScan 和 miRanda 推测注释的 circRNA 及其靶基因的潜在 miRNA 反应元件。结果。 RNA 测序检测到 28,978 个替代 circRNA。其中，有1063个表达有显着差异。与正常视网膜组织相比，四氧嘧啶诱导的糖尿病视网膜组织中 circKMT2E 上调两倍以上，表现出与 miR-204-5p 相反的表达趋势。生物信息学分析表明，circKMT2E在hsa-miR-204-5p上有4个种子序列。因此，推测circKMT2E在海绵miR-204-5p的基础上发挥功能，从而参与DR的发病过程。此外，miR-204-5p被推测能够结合SIRT1，SIRT1可以与其靶蛋白相互作用，并调节各种细胞功能，包括细胞炎症反应、增殖和凋亡。结论。 DR早期circKMT2E的上调可能参与其发病机制，并可能激活SIRT1信号通路，通过miR-204-5p的海绵功能来保护视网膜。