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子痫前期患者循环中微小RNA的表达谱:miR-885-5p水平升高的证据

Circulating microRNA expression profiles in pre-eclampsia: evidence of increased miR-885-5p levels.

作者信息

Sandrim V C, Luizon M R, Palei A C, Tanus-Santos J E, Cavalli R C

机构信息

Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.

Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.

出版信息

BJOG. 2016 Dec;123(13):2120-2128. doi: 10.1111/1471-0528.13903. Epub 2016 Feb 8.

Abstract

OBJECTIVE

To validate and to compare the circulating microRNA (miR) expression profiles between pre-eclampsia and healthy pregnant women, to perform correlation analysis of the differently expressed miRs with clinical and biochemical parameters, and to verify the extracellular localisation of miRs in apoptotic bodies, microvesicles, and exosomes.

DESIGN

A case-control study with a replication study.

SETTING

Pregnant women attending maternity hospitals in Southeastern Brazil.

POPULATION

Two obstetric white populations: a case-control study (19 pre-eclampsia and 14 healthy pregnant) and a replication study (eight pre-eclampsia and eight healthy pregnant).

METHODS

PCR-array with 84 different miRs was performed in plasma from five pre-eclampsia and four healthy pregnant women. In the case-control study, differently expressed miRs were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and correlated with clinical and biochemical parameters. The plasma was then fractioned to study the extracellular localisation of miRs.

MAIN OUTCOME MEASURES

Gene expression profiles of miRs.

RESULTS

From PCR-array, three miRs (miR-376c-3p, miR-19a-3p, and miR-19b-3p) were found to be down-regulated and the miR-885-5p was found to be up-regulated in pre-eclampsia compared with healthy pregnant women. In the validation step, miR-885-5p was the only significantly different miR (fold-change = 5.0, P < 0.05), which was confirmed in the replication study (fold-change = 4.5, P < 0.05). Moreover, miR-885-5p was significantly correlated with the hepatic enzyme aspartate transaminase (r = 0.66; P = 0.0034) and it was mostly associated with the exosomes (32-fold higher than apoptotic bodies).

CONCLUSIONS

miR-885-5p is increased in plasma from pre-eclampsia compared with healthy pregnant women, and it is released into circulation mainly inside exosomes. TWEETABLE ABSTRACT: miR-885-5p is increased in pre-eclampsia and is released into circulation mainly inside exosomes.

摘要

目的

验证并比较子痫前期孕妇与健康孕妇循环中微小RNA(miR)的表达谱,对差异表达的miR与临床和生化参数进行相关性分析,并验证miR在凋亡小体、微泡和外泌体中的细胞外定位。

设计

一项包含重复研究的病例对照研究。

地点

巴西东南部妇产医院的孕妇。

研究对象

两个产科白人群体:一项病例对照研究(19例子痫前期患者和14例健康孕妇)以及一项重复研究(8例子痫前期患者和8例健康孕妇)。

方法

对5例子痫前期患者和4例健康孕妇的血浆进行84种不同miR的PCR芯片检测。在病例对照研究中,使用定量实时逆转录聚合酶链反应(qRT-PCR)验证差异表达的miR,并与临床和生化参数进行相关性分析。然后对血浆进行分级分离以研究miR的细胞外定位。

主要观察指标

miR的基因表达谱。

结果

通过PCR芯片检测发现,与健康孕妇相比,子痫前期患者中有3种miR(miR-376c-3p、miR-19a-3p和miR-19b-3p)表达下调,miR-885-5p表达上调。在验证步骤中,miR-885-5p是唯一显著差异的miR(倍数变化=5.0,P<0.05),这在重复研究中得到证实(倍数变化=4.5,P<0.05)。此外,miR-885-5p与肝酶天冬氨酸转氨酶显著相关(r=0.66;P=0.0034),并且它主要与外泌体相关(比凋亡小体高32倍)。

结论

与健康孕妇相比,子痫前期患者血浆中miR-885-5p增加,并且它主要以外泌体形式释放到循环中。推文摘要:子痫前期患者中miR-885-5p增加,且主要以外泌体形式释放到循环中。

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