Weifang Medical University, Weifang 261053, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao 266071, China.
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao 266071, China; College of Medicine, Qingdao University, Qingdao 266071, China.
Gene. 2019 Aug 20;710:170-177. doi: 10.1016/j.gene.2019.05.054. Epub 2019 May 30.
Covalently closed, single-stranded circular RNAs (circRNAs) are a class of newly discovered endogenous RNAs involved in the pathological process of various types of diseases through sponging microRNAs (miRNAs). However, the role of circRNAs in diabetic cataract (DC) is unclear. Our previous studies have demonstrated that miR-204-5p was expressed more lowly in DC than the normal controls, but whether it relates to the sponge function of circRNAs remains unknown. This study aimed to identify differentially expressed circRNAs in DC tissues and investigate the interaction between circRNAs and miR-204-5p in the development of cataract. RNA-sequencing based circRNA expression profiling was determined in DC lens tissues as well as transparent lens tissues, and 1063 circRNAs were significantly differentially expressed in the DC group compared to the normal control group (p ≤ 0.05, fold change ≥ 2.0). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to predict the function of these differentially expressed circRNAs, and the top ten enriched GO entries and KEGG pathways were annotated. Expression levels of the two candidate circRNAs having conserved interaction with miR-204-5p were validated by qRT-PCR, showing that the change direction of these circRNAs was consistent with the RNA-sequencing data. Moreover, circKMT2E was up-regulated more than two folds in DC lens tissues compared with normal tissues, exhibiting an expression trend opposite to miR-204-5p. Bio-informatics analysis showed that there were totally four seed sequences of circKMT2E on hsa-miR-204-5p. Thus, we speculated that circKMT2E may function as a sponge molecule of miR-204-5p and play a role in the pathogenesis of DC. Although the exact mechanisms need further validation, our study found that the differentially expressed circRNAs was involved in the pathogenesis of DC, which can provide a new target for non-surgical treatment of DC.
共价闭合的单链环状 RNA（circRNA）是一类新发现的内源性 RNA，通过海绵吸附 microRNA（miRNA）参与各种疾病的病理过程。然而，circRNA 在糖尿病性白内障（DC）中的作用尚不清楚。我们之前的研究表明，miR-204-5p 在 DC 组织中的表达水平低于正常对照，但它是否与 circRNA 的海绵吸附功能有关尚不清楚。本研究旨在鉴定 DC 组织中差异表达的 circRNAs，并研究 circRNAs 与 miR-204-5p 在白内障发生发展中的相互作用。对 DC 晶状体组织和透明晶状体组织进行基于 RNA 测序的 circRNA 表达谱分析，与正常对照组相比，DC 组有 1063 个 circRNA 表达显著差异（p≤0.05，倍数变化≥2.0）。对这些差异表达的 circRNAs 进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，以预测其功能，注释了前 10 个富集的 GO 条目和 KEGG 通路。通过 qRT-PCR 验证了具有与 miR-204-5p 保守相互作用的两个候选 circRNAs 的表达水平，结果表明这些 circRNAs 的变化方向与 RNA 测序数据一致。此外，与正常组织相比，DC 晶状体组织中 circKMT2E 的表达水平上调了两倍以上，其表达趋势与 miR-204-5p 相反。生物信息学分析表明，hsa-miR-204-5p 上共有 4 个 circKMT2E 的种子序列。因此，我们推测 circKMT2E 可能作为 miR-204-5p 的海绵分子发挥作用，参与 DC 的发病机制。虽然确切的机制还需要进一步验证，但我们的研究发现差异表达的 circRNAs 参与了 DC 的发病机制，这可为非手术治疗 DC 提供新的靶点。
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