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循环 miR-31 和 miR-21 的下调与子痫前期有关。

Downregulations of circulating miR-31 and miR-21 are associated with preeclampsia.

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Obstetrics, The Central Hospital of Zibo, Zibo, Shandong Province, China.

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

出版信息

Pregnancy Hypertens. 2019 Jul;17:59-63. doi: 10.1016/j.preghy.2019.05.013. Epub 2019 May 15.

DOI:10.1016/j.preghy.2019.05.013
PMID:31487658
Abstract

MicroRNAs (miRNAs/miRs) are highly stable in circulating, which suppress target gene expression by base-pairing to the 3'-untranslated region. We compared the expressions of 3 circulating miRs (miR-31, miR-21, and miR-16), which are related to the control of cell apoptosis, invasion, angiogenesis and immune tolerance in non-pregnancy (n = 10), 20-34 gestational weeks normal pregnancy (20-34 GW NP, n = 20), early onset preeclampsia (EOPE, n = 20), 34-41 gestational weeks normal pregnancy (34-41 GW NP, n = 20) and late onset preeclampsia (LOPE, n = 20). Using quantitative RT-PCR, we found the levels of miR-31, miR-21 and miR-16 changed throughout different stages of pregnancy with the non-pregnancy as the calibrator. The plasma miR-31 levels were significantly down-regulated in EOPE rather than in LOPE when compared to gestational age matched normal pregnancy (P < 0.001). MiR-21 levels were significantly lower in LOPE compared to healthy controls (P < 0.001), while no significant difference was found between EOPE and 20-34 gestational weeks normal pregnancy (P = 0.376). The miR-16 expressions were at similar levels between preeclampsia (PE) and normal pregnancy. Receiver operating characteristic (ROC) curve analyses indicated the miR-31 differentiated EOPE patients from healthy controls with an area under the curve (AUC) of 0.875 with 95.0% sensitivity and 70.0% specificity. ROC curves also discriminated the LOPE patients from healthy pregnancy with an AUC of 0.793, 65.1% sensitivity and 90.3% specificity for plasma miR-21 levels. This study is the first to demonstrate the difference, and circulating miR-31 may serve as a diagnostic biomarker for early onset preeclampsia meanwhile miR-21 might be a diagnostic biomarker for late onset preeclampsia.

摘要

微小 RNA(miRNAs/miRs)在循环中高度稳定,通过与 3'非翻译区碱基配对来抑制靶基因表达。我们比较了 3 种循环 miRNA(miR-31、miR-21 和 miR-16)的表达水平,这些 miRNA 与细胞凋亡、侵袭、血管生成和免疫耐受的控制有关,它们存在于非妊娠(n=10)、20-34 孕周正常妊娠(20-34 GW NP,n=20)、早发型子痫前期(EOPE,n=20)、34-41 孕周正常妊娠(34-41 GW NP,n=20)和晚发型子痫前期(LOPE,n=20)中。通过定量 RT-PCR,我们发现 miR-31、miR-21 和 miR-16 的水平在妊娠的不同阶段都发生了变化,以非妊娠为校准器。与胎龄匹配的正常妊娠相比,EOPE 患者的血浆 miR-31 水平明显下调(P<0.001)。与健康对照组相比,LOPE 患者的 miR-21 水平明显降低(P<0.001),而 EOPE 与 20-34 孕周正常妊娠之间无显著差异(P=0.376)。子痫前期(PE)与正常妊娠的 miR-16 表达水平相似。受试者工作特征(ROC)曲线分析表明,miR-31 能够区分 EOPE 患者和健康对照者,曲线下面积(AUC)为 0.875,敏感性为 95.0%,特异性为 70.0%。ROC 曲线也可以区分 LOPE 患者和正常妊娠者,血浆 miR-21 水平的 AUC 为 0.793,敏感性为 65.1%,特异性为 90.3%。本研究首次证明了这种差异,循环 miR-31 可能成为早发型子痫前期的诊断生物标志物,而 miR-21 可能成为晚发型子痫前期的诊断生物标志物。

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