Differential Expressions of microRNAs and Transfer RNA-derived Small RNAs: Potential Targets of Choroidal Neovascularization
Differential Expressions of microRNAs and Transfer RNA-derived Small RNAs: Potential Targets of Choroidal Neovascularization
复制标题
microRNA 和转移 RNA 衍生的小 RNA 的差异表达：脉络膜新生血管形成的潜在靶点。
DOI：
10.1080/02713683.2019.1625407
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发表时间：
2019-06-16
影响因子：
2
通讯作者：
Zhou, Yedi
中科院分区：
文献类型：
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作者：
Zhang, Liwei;Liu, Shaohua;Zhou, Yedi
摘要目的：脉络膜新生血管（CNV）是新生血管性年龄相关性黄斑变性（AMD）的主要临床特征之一。小的非编码RNA，例如微小RNA（miRNA）和转移RNA衍生的小RNA（tsRNA）在多种生物学功能中发挥关键作用。本研究的目的是探讨miRNAs和tsRNAs在CNV中的作用和可能的功能。方法：采用激光光凝法建立小鼠CNV模型。采用小分子RNA测序（RNA-Seq）技术检测CNV组和对照组RPE-脉络膜-巩膜复合体中miRNAs和tsRNAs的表达谱。通过qRT-PCR验证选择的改变的miRNA和tsRNA。通过信息学分析预测靶基因，并与先前改变的mRNAs的微阵列研究相结合。进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径分析以揭示这些靶基因最富集的生物学功能和信号传导途径。结果：CNV小鼠RPE-脉络膜-巩膜复合体中共有79个miRNAs和72个tsRNAs发生了显著变化。GO分析显示，所选miRNAs的改变的靶基因最富集在免疫应答、膜和肽结合的组成部分，而tsRNAs的改变的靶基因最富集在免疫系统过程的调节、细胞外区域和核心启动子结合。此外，KEGG通路分析表明，miRNAs和tsRNAs的靶基因分别在造血细胞谱系和NOD样受体信号通路中富集。结论：我们的研究证实了CNV模型中miRNAs和tsRNAs的差异表达，这些改变的miRNAs和tsRNAs可能成为治疗新生血管性AMD患者CNV的新的潜在靶点。
ABSTRACT Purpose: Choroidal neovascularization (CNV) is one of the major clinical characteristics of neovascular age-related macular degeneration (AMD). Small non-coding RNAs, such as microRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play key roles in diverse biological functions. The purpose of the study was to investigate the roles and possible functions of the miRNAs and tsRNAs in CNV. Methods: The mouse model of laser-induced CNV was conducted by laser photocoagulation. The expression profiles of miRNAs and tsRNAs were accessed by small RNA sequencing (RNA-Seq) in RPE-choroid-sclera complexes of mice in CNV group and control group. Selected altered miRNAs and tsRNAs were validated by qRT-PCR. Target genes were predicted by informatics analysis and intersected with the previous microarray study of altered mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to reveal the biological functions and signaling pathways with which these target genes are most enriched. Results: The results revealed that 79 miRNAs and 72 tsRNAs in total were significantly altered in the RPE-choroid-sclera complexes of CNV mice. GO analysis revealed that the altered target genes of the selected miRNAs most enriched in immune response, integral component of membrane and peptide binding, while the altered target genes of tsRNAs most enriched in regulation of immune system process, extracellular region, and core promoter binding. Moreover, KEGG pathway analysis demonstrated that altered target genes of miRNAs and tsRNAs most enriched in hematopoietic cell lineage and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, respectively. Conclusions: Our study identified differential expressions of miRNAs and tsRNAs in CNV model, and these altered miRNAs and tsRNAs might be novel potential targets in treating CNVs in patients with neovascular AMD.