Circulatory miRNA biomarkers of metabolic syndrome
Circulatory miRNA biomarkers of metabolic syndrome
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DOI：
10.1007/s00592-019-01406-6
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发表时间：
2020-02-01
影响因子：
3.8
通讯作者：
Cameron-Smith, D.
中科院分区：
文献类型：
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作者：
Ramzan, F.;D'Souza, R. F.;Cameron-Smith, D.
目的循环microRNAs(c-miRNAs)在心脏代谢性疾病的分子调控中发挥重要作用。然而，当危险因素升高时，如代谢综合征(METS)，miRNA表达异常是否会发生，目前还知之甚少。这项研究量化了甲型肝炎患者和健康人群中c-miRNA的表达，进一步研究了基因途径与潜在发病机制的关系。方法采用定量聚合酶链式反应技术检测40例女性(20例健康和20例蛋氨酸)和39例男性(20例健康和19例蛋氨酸)血浆中26个miRNAs的表达。在计算机分析中，研究了失调的miRNAs的生物学效应。在20名女性(10名健康女性和10名大梅氏症患者)的独立队列中，进一步证实了miRNA表达异常。结果调整年龄和性别的回归模型显示，miR-15a-5p、miR-17-5p、miR-370-3p和miR-375是METS的重要预测因子。对验证队列中预测性miRNAs的分析加强了与miR-15a-5p和miR-17-5p表达的关系。这些miRNAs共享参与代谢途径调控的基因，包括胰岛素、WNT、脂肪酸代谢和AMPK。结论miR-15a-5p和miR-17-5p是METS的预测生物标志物，不分性别，进一步证实了c-miRNAs与已知的心脏代谢性疾病代谢紊乱途径的关系。
Aims Circulatory microRNAs (c-miRNAs) exert important roles in the molecular dysregulation of cardio-metabolic diseases. However, little is known whether dysregulated miRNA expression occurs when risk factors are elevated, as in the metabolic syndrome (MetS). This study quantified c-miRNA expression in individuals with MetS compared to healthy, further examining the relationship of gene pathways with the underlying pathogenesis. Methods Expression of 26 miRNAs was quantified in plasma from 40 women (20 healthy and 20 MetS) and 39 men (20 healthy and 19 MetS) by qPCR. In silico analysis was performed to investigate biological effects of the dysregulated miRNAs. Dysregulated miRNA expression was further validated in an independent cohort of 20 women (10 healthy and 10 MetS). Results Regression model adjusted for age and sex identified miR-15a-5p, miR-17-5p, miR-370-3p and miR-375 as important predictors of MetS presence. Analysis of predictive miRNAs in the validation cohort strengthened the relationship with miR-15a-5p and miR-17-5p expression. These miRNAs share genes involved in the regulation of metabolic pathways including insulin, wnt, fatty acid metabolism and AMPK. Conclusions miR-15a-5p and miR-17-5p were identified as predictive biomarkers of MetS, irrespective of sexes, further demonstrating the relationship of c-miRNAs to known pathways of metabolic disturbances present in cardio-metabolic diseases.