A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2024-05-03 DOI:10.3390/ncrna10030030

Gantsetseg Garmaa, S. Bunduc, T. Kói, Péter Hegyi, D. Csupor, Dariimaa Ganbat, F. Dembrovszky, F. Meznerics, Ailar Nasirzadeh, C. Barbagallo, G. Kökény

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Abstract

Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients’ blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies.

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慢性肾脏病中 microRNA 图谱研究的系统性回顾和元分析

慢性肾脏病（CKD）对健康造成的负担与日俱增。有证据表明 miRNA 在诊断 CKD 中的重要性，但相关报道并不一致。本研究旨在从人类和鼠类 CKD 的无假设 miRNA 图谱研究中确定新型 miRNA 生物标记物和潜在治疗靶点。研究人员在五个数据库中进行了全面的文献检索。对肾脏疾病、样本类型、疾病阶段和物种进行了分组分析。采用稳健等级聚合（RRA）和计票分析法对符合条件的 38 项人类研究和 12 项鼠类研究进行了分析。利用 DIANA-miRPath v4.0 和 MIENTURNET 对每种肾病的 miRNA 特征进行了基因组富集分析。结果确定了每种肾病的顶级靶基因、基因本体术语、miRNA 与靶基因之间的相互作用网络和分子通路。根据计票分析，145 个 miRNA 在人类肾脏疾病中出现失调，32 个 miRNA 在小鼠 CKD 模型中出现失调。通过RRA，狼疮性肾炎（LN）肾组织中的miR-26a-5p明显减少，而LN患者血液样本中的miR-107减少。在这两个物种中，上皮-间质转化、Notch、mTOR 信号转导、细胞凋亡、G2/M 检查点和缺氧是最富集的通路。这些miRNA特征及其靶基因必须在大型患者队列研究中得到验证。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.

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