通过多源基因表达谱综合分析揭示缺血性卒中中circRNA介导的ceRNA网络
Unveiling circRNA-mediated ceRNA networks in ischemic stroke by integrative analysis of multi-source gene expression profiling.
作者信息
Zhang Ya, Zhang Xiao-Ou
机构信息
Shanghai Key Laboratory of Maternal and Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
出版信息
Heliyon. 2024 Aug 27;10(17):e36988. doi: 10.1016/j.heliyon.2024.e36988. eCollection 2024 Sep 15.
BACKGROUND
Circular RNAs (circRNAs) are emerging as potential therapeutic targets for ischemic stroke (IS) due to their regulatory roles in inflammation and apoptosis. This study aimed to develop a comprehensive and robust IS-specific competing endogenous RNA (ceRNA) network to facilitate the identification of novel diagnostic and therapeutic targets.
METHODS
We integrated expression data from 15 IS studies using the Rank-In algorithm to minimize batch effects. Differentially expressed circRNAs, miRNAs, and mRNAs were identified by comparing IS and control samples. Functional enrichment analysis of differentially expressed circRNA host genes revealed significantly enriched pathways and Gene Ontology (GO) terms relevant to IS pathogenesis. We further predicted miRNA-circRNA and mRNA-miRNA interactions, enabling the construction of a comprehensive ceRNA network to identify circRNA-related genes with diagnostic potential for IS.
RESULTS
Integrated analysis revealed 199 differentially expressed circRNAs, 103 miRNAs, and 1736 mRNAs in IS patients. Functional enrichment analysis implicated these molecules in relevant pathways like the neurotrophin signaling pathway and p53 signaling pathway. The constructed circRNA-miRNA-mRNA regulatory network provided insights into potential mechanisms underlying IS. Three circRNA-related genes (RGS2, CDK5R1, and NSF) displayed promising diagnostic potential for IS when combined.
CONCLUSIONS
We successfully constructed a robust and informative IS-specific ceRNA network by integrating data from diverse sources. This network identified differentially expressed RNAs and revealed enriched pathways potentially involved in IS pathogenesis. Notably, our analysis identified CDK5R1, RGS2, and NSF as potential diagnostic biomarkers for IS. This study sheds light on a circRNA-mediated regulatory network with potential diagnostic and therapeutic implications for ischemic stroke.
背景
环状RNA（circRNAs）因其在炎症和细胞凋亡中的调节作用，正逐渐成为缺血性中风（IS）潜在的治疗靶点。本研究旨在构建一个全面且可靠的缺血性中风特异性竞争性内源RNA（ceRNA）网络，以促进新型诊断和治疗靶点的识别。
方法
我们使用Rank-In算法整合了来自15项缺血性中风研究的表达数据，以最小化批次效应。通过比较缺血性中风患者和对照样本，鉴定出差异表达的circRNAs、miRNAs和mRNAs。对差异表达的circRNA宿主基因进行功能富集分析，揭示了与缺血性中风发病机制相关的显著富集通路和基因本体（GO）术语。我们进一步预测了miRNA-circRNA和mRNA-miRNA相互作用，从而构建了一个全面的ceRNA网络，以识别具有缺血性中风诊断潜力的circRNA相关基因。
结果
整合分析显示，缺血性中风患者中有199个差异表达的circRNAs、103个miRNAs和1736个mRNAs。功能富集分析表明，这些分子参与了神经营养因子信号通路和p53信号通路等相关通路。构建的circRNA-miRNA-mRNA调控网络为缺血性中风的潜在机制提供了见解。三个circRNA相关基因（RGS2、CDK5R1和NSF）联合使用时，对缺血性中风显示出有前景的诊断潜力。
结论
我们通过整合来自不同来源的数据，成功构建了一个强大且信息丰富的缺血性中风特异性ceRNA网络。该网络鉴定出差异表达的RNAs，并揭示了可能参与缺血性中风发病机制的富集通路。值得注意的是，我们的分析确定CDK5R1、RGS2和NSF为缺血性中风的潜在诊断生物标志物。本研究揭示了一个circRNA介导的调控网络，对缺血性中风具有潜在的诊断和治疗意义。
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