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小于胎龄儿和适于胎龄儿肥胖儿童循环miRNA特征的初步研究

Pilot study on circulating miRNA signature in children with obesity born small for gestational age and appropriate for gestational age.

作者信息

Marzano F, Faienza M F, Caratozzolo M F, Brunetti G, Chiara M, Horner D S, Annese A, D'Erchia A M, Consiglio A, Pesole G, Sbisà E, Inzaghi E, Cianfarani S, Tullo A

机构信息

Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies-IBIOM, CNR, Bari, Italy.

Department of Biomedical Sciences and Human Oncology, Section of Pediatrics, University of Bari "A. Moro,", Bari, Italy.

出版信息

Pediatr Obes. 2018 Dec;13(12):803-811. doi: 10.1111/ijpo.12439. Epub 2018 Aug 29.

Abstract

BACKGROUND

Children born small for gestational age (SGA) are at increased risk of metabolic dysfunction. Dysregulation of specific microRNAs (miRNAs) contributes to aberrant gene expression patterns underlying metabolic dysfunction.

OBJECTIVE

We aimed to determine and compare circulating miRNA (c-miRNA) profile of SGA and appropriate for gestational age (AGA) children with obesity and with normal weight, in order to identify biomarkers for early detection of increased risk of developing metabolic dysfunction in SGA and AGA children with obesity.

METHODS

Small non-coding RNAs from serum of 15 SGA children with obesity (OB-SGA), 10 SGA children with normal weight (NW-SGA), 17 AGA children with obesity (OB-AGA) and 12 AGA children with normal weight (NW-AGA) (mean age 11.2 ± 2.6) have been extracted and sequenced in order to detect and quantify miRNA expression profiles.

RESULTS

RNA-seq analyses showed 28 miRNAs dysregulated in OB-SGA vs. NW-SGA and 19 miRNAs dysregulated in OB-AGA vs. NW-AGA. Among these, miR-92a-3p, miR-122-5p, miR-423-5p, miR-484, miR-486-3p and miR-532-5p were up regulated, and miR-181b-5p was down regulated in both OB-SGA and OB-AGA compared with normal weight counterparts. Pathway analysis and miRNA target prediction suggested that these miRNAs were particularly involved in insulin signalling, glucose transport, insulin resistance, cholesterol and lipid metabolism.

CONCLUSION

We identified a specific profile of c-miRNAs in SGA and AGA children with obesity compared with SGA and AGA children with normal weight. These c-miRNAs could represent specific biomarkers for early detection of increased risk of developing metabolic dysfunction in SGA and AGA children with obesity.

摘要

背景

小于胎龄儿(SGA)出生时代谢功能障碍风险增加。特定微小RNA(miRNA)的失调导致代谢功能障碍背后的异常基因表达模式。

目的

我们旨在确定并比较肥胖和体重正常的SGA及适于胎龄儿(AGA)儿童的循环miRNA(c-miRNA)谱,以识别可早期检测肥胖的SGA和AGA儿童发生代谢功能障碍风险增加的生物标志物。

方法

已从15名肥胖的SGA儿童(OB-SGA)、10名体重正常的SGA儿童(NW-SGA)、17名肥胖的AGA儿童(OB-AGA)和12名体重正常的AGA儿童(NW-AGA)(平均年龄11.2±2.6岁)的血清中提取并测序了小非编码RNA,以检测和定量miRNA表达谱。

结果

RNA测序分析显示,与NW-SGA相比,OB-SGA中有28种miRNA失调;与NW-AGA相比,OB-AGA中有19种miRNA失调。其中,与体重正常的对应儿童相比,miR-92a-3p、miR-122-5p、miR-423-5p、miR-484、miR-486-3p和miR-532-5p在OB-SGA和OB-AGA中均上调,而miR-181b-5p下调。通路分析和miRNA靶标预测表明,这些miRNA特别参与胰岛素信号传导、葡萄糖转运、胰岛素抵抗、胆固醇和脂质代谢。

结论

与体重正常的SGA和AGA儿童相比,我们在肥胖的SGA和AGA儿童中鉴定出了特定的c-miRNA谱。这些c-miRNA可能代表可早期检测肥胖的SGA和AGA儿童发生代谢功能障碍风险增加的特异性生物标志物。

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