Comprehensive analysis of differentially expressed microRNAs and mRNAs involved in diabetic corneal neuropathy

Comprehensive analysis of differentially expressed microRNAs and mRNAs involved in diabetic corneal neuropathy
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糖尿病角膜神经病变中差异表达的microRNA和mRNA的综合分析

DOI:
10.1016/j.lfs.2020.118456
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发表时间:
2020
期刊:
影响因子:
6.1
通讯作者:
Xie Lixin
Xie Lixin
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Yuan;Jiang Hui;Dou Shengqian;Zhang Bin;Qi Xia;Li Jing;Zhou Qingjun;Li Weina;Chen Chen;Wang Qun;Xie Lixin

文献摘要

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目的角膜神经纤维来源于三叉神经节眼段。在这里,我们通过对糖尿病和正常TG组织中的微小RNA(miRNA)和信使RNA(mRNA)进行测序,旨在揭示参与糖尿病角膜神经病变发病机制的潜在miRNA、mRNA及其相互作用网络。主要方法我们进行RNA测序,系统地筛选出糖尿病小鼠和正常小鼠TG组织中差异表达的miRNA和mRNA。进行功能富集分析以说明差异表达的mRNA(DEmRNA)的生物学功能。在此基础上,通过生物信息学方法构建miRNA-mRNA调控网络,探讨miRNAs在糖尿病角膜神经病变发病机制中的调控作用。关键发现测序分析显示,与正常TG组织相比,糖尿病TG组织中有68个miRNAs和114个mRNAs存在差异表达。功能分析表明DEmRNA参与了糖尿病相关的生物学过程。在应用优化的方法预测miRNA-mRNA对之后,推断miRNA-mRNA相互作用网络。本研究初步验证了miR-350- 5 p与Mup 20、miR-592- 5 p与Angpt 17、miR-351- 5 p与Elov 16的表达及其相关性。
AimsCorneal nerve fibers are derived from the ophthalmic division of the trigeminal ganglion (TG). Here, by sequencing of microRNAs (miRNAs) and messenger RNAs (mRNAs) from diabetic and normal TG tissues, we aimed to uncover potential miRNAs, mRNAs, and the network of their interactions involved in the pathogenesis of diabetic corneal neuropathy.Main methodsWe performed RNA sequencing to systematically screen out differentially expressed miRNAs and mRNAs in TG tissues from diabetic and normal mice. Functional enrichment analyses were performed to illustrate the biological functions of differentially expressed mRNAs (DEmRNAs). Following this, miRNA-mRNA regulatory networks were built by means of bioinformatics methods to suggest regulatory role for miRNAs in the pathogenesis of diabetic corneal neuropathy. Finally, the credibility of the sequencing-based results was validated using qRT-PCR.Key findingsSequencing analyses disclosed that 68 miRNAs and 114 mRNAs were differentially expressed in diabetic TG tissues compared with normal TG samples. The functional analyses showed that DEmRNAs participated in diabetes-related biological processes. After applying an optimized approach to predict miRNA–mRNA pairs, a miRNA-mRNA interacting network was inferred. Subsequently, the expression and correlation of miR-350-5p and Mup20, miR-592-5p and Angptl7 as well as miR-351-5p andElovl6were preliminarily validated.SignificanceOur study provides a systematic characterization of miRNA and mRNA expression in the TG during diabetic corneal neuropathy and will contribute to the development of clinical diagnostic and therapeutic strategies for diabetic corneal neuropathy.