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在代谢综合征患者中,尿中miRNA - 29a - 3p水平通过对胰岛素样生长因子1(IGF1)的调控与代谢参数相关。

Urinary miRNA-29a-3p levels are associated with metabolic parameters via regulation of IGF1 in patients with metabolic syndrome.

作者信息

Lin Xihua, Luo Cheng, He Dongjuan, Matro Erik, Chen Qilong, Li Hong, Zhou Jiaqiang

机构信息

Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.

Department of Endocrinology, The Third Hospital of Quzhou, Quzhou, Zhejiang 324003, P.R. China.

出版信息

Biomed Rep. 2019 Apr;10(4):250-258. doi: 10.3892/br.2019.1195. Epub 2019 Feb 21.

Abstract

Circulating microRNAs (miRNAs or miRs) have been demonstrated to serve as diagnostic and prognostic biomarkers in metabolic syndrome (MetS). The role of urinary miRNAs in MetS diagnosis remains unknown. Here, elevated miR-29a-3p levels were observed in urine samples of patients with MetS compared with control subjects using a microarray analysis (n=4/group) and validation via reverse transcription-quantitative polymerase chain reaction (n=40/group). Associations between urinary miR-29a-3p levels and parameters associated with metabolism, such as adiposity, insulin resistance, lipid profiles and hepatic enzymes were further assessed. Multiple linear regression analyses revealed that urinary miR-29a-3p levels were independently correlated with fasting insulin (β=0.561; P<0.001), high density lipoprotein-cholesterol (β=0.242; P<0.001) and body mass index (β=-0.141; P<0.05). The area under the receiver operating characteristic curve was 0.776 and miR-29a-3p had a diagnostic value for MetS with 68.2% sensitivity and 77.3% specificity. Furthermore, insulin-like growth factor 1 was identified as a target of miR-29a-3p by searching bioinformatics databases and was validated by dual-luciferase reporter and western blot assays. In conclusion, elevated urinary miR-29a-3p levels were positively associated with MetS and demonstrated to have a potential value as biomarkers in the diagnosis of MetS. The findings provided a better understanding of the role of urinary miRNAs in pathogenesis of MetS.

摘要

循环微RNA(miRNA或miR)已被证明可作为代谢综合征(MetS)的诊断和预后生物标志物。尿miRNA在MetS诊断中的作用尚不清楚。在此,通过微阵列分析(每组n = 4)和逆转录定量聚合酶链反应验证(每组n = 40),观察到与对照受试者相比,MetS患者尿样中miR-29a-3p水平升高。进一步评估了尿miR-29a-3p水平与代谢相关参数之间的关联,如肥胖、胰岛素抵抗、血脂谱和肝酶。多元线性回归分析显示,尿miR-29a-3p水平与空腹胰岛素(β = 0.561;P < 0.001)、高密度脂蛋白胆固醇(β = 0.242;P < 0.001)和体重指数(β = -0.141;P < 0.05)独立相关。受试者工作特征曲线下面积为0.776,miR-29a-3p对MetS具有诊断价值,敏感性为68.2%,特异性为77.3%。此外,通过搜索生物信息学数据库确定胰岛素样生长因子1为miR-29a-3p的靶标,并通过双荧光素酶报告基因和蛋白质印迹分析进行了验证。总之,尿miR-29a-3p水平升高与MetS呈正相关,并被证明在MetS诊断中具有作为生物标志物的潜在价值。这些发现有助于更好地理解尿miRNA在MetS发病机制中的作用。

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