A meta-analysis of microRNA expression profiling studies in heart failure
A meta-analysis of microRNA expression profiling studies in heart failure
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DOI：
10.1007/s10741-020-10071-9
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发表时间：
2021-01-14
影响因子：
4.6
通讯作者：
Javanmard, Shaghayegh Haghjooy
中科院分区：
文献类型：
--
作者：
Gholaminejad, Alieh;Zare, Nasrin;Javanmard, Shaghayegh Haghjooy
心力衰竭（heartfailure，HF）是许多心血管疾病的主要并发症，其发病率和死亡率都很高。早期诊断和预防受到缺乏信息性生物标志物的阻碍。本研究的目的是对HF中的miRNA表达谱研究进行荟萃分析，以确定新的候选生物标志物或/和治疗靶点。对PubMed进行了一项与HF相关的miRNA表达研究的全面文献检索。使用投票计数和稳健的秩聚合荟萃分析方法来识别HF-miR的显著Meta特征。鉴定HF-miR的靶标，并进行网络构建和基因集富集分析（GSEA）以鉴定受miRNAs失调影响最大的基因和认知途径。文献检索确定了45项与CHF相关的miRNA表达研究。对于3种上调的（miR-21、miR-214和miR-27 b）和13种下调的（miR-133 a、miR-29 a、miR-29 b、miR-451、miR-185、miR-133 b、miR-30 e、miR-30 b、miR- 1、miR-150、miR- 486、miR-149和miR-16- 5 p）miRNA，鉴定了共享的元签名。网络性质显示miR-29 a、miR- 21、miR-29 b、miR-1、miR-16、miR-133 a和miR-133 b具有最大程度的中心性。GESA鉴定了HF中作为HF-miR靶点的信号传导和社区途径中功能相关的基因组。miRNA表达荟萃分析鉴定了16个在HF中差异表达的高度显著的HF-miR。需要在大型患者队列中进行进一步验证，以确认这些miR作为HF生物标志物和治疗靶点的意义。
Heart failure (HF) is a major consequence of many cardiovascular diseases with high rate of morbidity and mortality. Early diagnosis and prevention are hampered by the lack of informative biomarkers. The aim of this study was to perform a meta-analysis of the miRNA expression profiling studies in HF to identify novel candidate biomarkers or/and therapeutic targets. A comprehensive literature search of the PubMed for miRNA expression studies related to HF was carried out. The vote counting and robust rank aggregation meta-analysis methods were used to identify significant meta- signatures of HF-miRs. The targets of HF-miRs were identified, and network construction and gene set enrichment analysis (GSEA) were performed to identify the genes and cognitive pathways most affected by the dysregulation of the miRNAs. The literature search identified forty-five miRNA expression studies related to CHF. Shared meta-signature was identified for 3 up-regulated (miR-21, miR-214, and miR-27b) and 13 down-regulated (miR-133a, miR-29a, miR-29b, miR-451, miR-185, miR-133b, miR-30e, miR-30b, miR- 1, miR-150, miR- 486, miR-149, and miR-16-5p) miRNAs. Network properties showed miR-29a, miR- 21, miR-29b, miR-1, miR-16, miR- 133a, and miR-133b have the most degree centrality. GESA identified functionally related sets of genes in signaling and community pathways in HF that are the targets of HF-miRs. The miRNA expression meta-analysis identified sixteen highly significant HF-miRs that are differentially expressed in HF. Further validation in large patient cohorts is required to confirm the significance of these miRs as HF biomarkers and therapeutic targets.