Mesh : Alloxan Diabetes Mellitus Diabetic Retinopathy / genetics Humans MicroRNAs / genetics metabolism RNA, Circular / genetics Retina Signal Transduction Sirtuin 1 / genetics metabolism

来  源:   DOI:10.1155/2022/7188193   PDF(Pubmed)

Abstract:
UNASSIGNED: To explore the changes of circRNAs in the retina of diabetic patients without diabetic retinopathy (DR) to screen latent protective factor.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要:
探讨无糖尿病视网膜病变(DR)的糖尿病患者视网膜中circRNAs的变化,以筛选潜在的保护因子。
本研究涉及来自三个糖尿病供体的视网膜的测序数据,所述三个糖尿病供体在最终眼睛检查时不具有视网膜的明显病理特征,并且三个健康的供体样品。在这里,我们在基因本体论和KEGG通路分析的基础上进行了生物信息学分析,以揭示circRNAs的表达模式和特征。然后,应用测序数据推断所选择的circRNAs与miR-204-5p之间的相互作用。使用TargetScan和miRanda推测注释的circRNAs及其靶基因的潜在miRNA响应元件。
RNA测序检测到28,978个替代circRNAs。其中,1063则表示出差别显著。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上有四个种子序列。因此,推测circKMT2E在构建miR-204-5p的基础上具有功能,以参与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,调节各种细胞功能,包括细胞炎症反应,扩散,以及细胞凋亡。
circKMT2E在DR早期的上调可能与DR的发病有关,可能通过miR-204-5p的海绵功能激活SIRT1信号通路保护视网膜。
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